A new design and configuration for tree stump cutting tooth and its corresponding holding bracket. Notch(s) on the tooth and rib(s) on the bracket are used to allow fast installation of tooth without gauging, reduced the time needed for such necessary tasks. The notch/rib structure also increases the clamping power of the bracket, reducing the possibility that any tooth would fly out, due to the centrifugal force, and cause injury. Wide notches are employed on certain heavy-duty tooth and allow the installation to be done quickly in two positions, and a small range in between the two positions.

The present invention relates generally to design and configuration of teeth and corresponding holding brackets used on machines for tree stump cutting and grinding. These brackets are sometimes referred to as "pocket" in the industry.
Modem tree stump cutting and grinding machines in general have a rotary disc (or wheel) driven by motor; the disc has multiple teeth attached at the outer edge of the disc so that when the disc is spinning/rotating, the teeth on the edge repeatedly cuts towards the tree stump, or any work piece.
A tooth/pocket design is discussed and disclosed in U.S. Pat. No. 5,279,435. All prior art in the implementation of such tooth/pocket design, however, has at least three disadvantages:                (1) when a new tooth is installed into its pocket, the length of its protrusion outward from the pocket (the portion containing the cutting carbide tip) must be properly gauged; uneven length on the protruding teeth usually results in higher damage rate on the teeth;        (2) to prevent uneven length on the protruding teeth, the installation time needed will increase, depending on the number of teeth being replaces/installed;        (3) the contact surface between the tooth and its pocket is flat; if the clamping power provided by the pocket is lessened, through wear and tear, the tooth could slip out by the very centrifugal force at work;

Configurations and designs for stump grinding teeth and corresponding holding brackets


An electronic part equipped unit includes a case body having a first recess portion for containing an electronic part and a second recess portion for containing a relay terminal and a ground terminal which are connected to the electronic part through leads, a wire side terminal to which a middle portion of a wire is attached, a cover member to which the wire side terminal is attached, and a shortcircuit preventing cover that covers a bottom wall and a side wall of the case body at a position corresponding to the second recess portion. The wire side terminal is brought into contact with the relay terminal when the cover member to which the wire side terminal is attached is fitted to the second recess portion of the case body.

The present invention relates to an electronic part equipped unit including an electronic part at inside of a case body and attached to a middle portion of a wire.
For example, in various sensors mounted to an automobile or the like, noise from a noise source having a high frequency component, such as a horn or a wire, and external noise from a neon sign or the like, an induction noise or the like are conducted to the sensors through a wire, and there is a concern of bringing about an erroneous operation thereby. In order to remove the noise, development of an electronic part equipped unit (noise prevention piece) has been promoted.
In FIG. 9, a reference 1 designates a wire. Further, a reference 2 designates an electronic part equipped unit connected to a middle portion 3 of the wire 1. The electronic part equipped unit 2 includes a case body 4 having an electronic part containing recess portion and a fitting connection recess portion, a containing recess portion cover 6 consecutively aligned to the case body 4 by way of a hinge 5 for covering the electronic part containing recess portion, a resin locking portion 7 formed at the containing recess portion cover 6 and locked to an attaching counter party, an electronic part 9 which is contained in the electronic part containing recess portion and in which a pair of leads 8a and 8b are extended to the fitting connection recess portion, a relay terminal 10 brought into contact with the lead 8a on one side, a ground terminal 12 made of a metal which is brought into contact with the lead 8b on other side and in which a portion projected from the fitting connection recess portion is formed as a ground portion 11, and a cover attached wire 15 which includes a wire side terminal 13 and a cover member 14 and attached to the middle portion of the wire 1 and in which the wire side terminal 13 is brought into contact with the relay terminal 10 and the cover member 14 is fitted to the fitting connection recess portion.
In the electronic part equipped unit 2, the fitting connection recess portion and the cover member 14 fitted thereto are disposed between the resin locking portion 7 and the ground portion 11. The cover member 14 and the fitting connection recess portion are fitted to each other with a cover side fitting portion 16 and a projected locking portion 17.
When the electronic part equipped unit 2 is attached to a vehicle, first, the resin locking portion 7 is inserted to a seat face made of a metal of an attaching counter party to be provisionally fixed, next, the ground portion 11 of the ground terminal 12 is fastened by a screw to connect to thereby finish fixing a total thereof.
Further, as a technology with regard to the electronic part equipped unit 2, for example, a disclosed technology of Patent Reference 1 is described below.
[Patent Reference 1] JP-A-2006-109587
Meanwhile, according to the electronic part equipped unit 2, in order to stabilize a state of connecting the one lead 8a of the electronic part 9 and the relay terminal 10, further, in order to stabilize a state of connecting the other lead 8b of the electronic part 9 and the ground terminal 12, it is conceived preferable to apply welding. Although it is necessary to form a through hole for welding (welding hole) at the bottom wall of the case body 4 at a position of the fitting connection recess portion, the welding hole is not needed after welding to stay to be opened. Therefore, there poses a problem that after attaching the electronic part equipped unit 2 to a vehicle, when a foreign matter having a conductivity is brought into contact with the welded portion and a seat face made of a metal of the vehicle, shortcircuit is brought about.


Thiophosphine compounds (also named phosphine sulfide compounds) and their use for making polymerizable compositions which after polymerization give optically transparent articles, such as ophthalmic lenses, having improved mechanical and optical properties and in particular having an improved UV cut.

The present invention relates in general to thiophosphine compounds (also named phosphine sulfide compounds) and their use for making polymerizable compositions which after polymerisation give optically transparent articles, such as ophthalmic lenses, having improved mechanical and optical properties and in particular having an improved UV cut.
The use of polymerizable compositions comprising thiourethane monomers is well known for making ophthalmic lenses. The thus obtained ophthalmic lenses exhibit a unique combination of mechanical and optical properties.
Nevertheless, there is still a need for improved materials for making ophthalmic lenses and in particular for materials having an improved UV cut, without adversely affecting the other required mechanical and optical properties.

Thiophosphine compounds and methods of making polymerizable compositions containing them and their use for making ophthalmic lenses

Essilor International Compagnie Generale d'Optique


A power-driven hand tool is disclosed, comprising a tool spindle that can be driven in a rotational oscillatory manner about its longitudinal axis and that is designed to carry a tool, and further comprising a transmission housing, in which there is carried an eccentric coupling drive for driving the tool spindle and from which the tool spindle projects outwardly with one end, wherein, for the purpose of mass compensation of the oscillatory motion of the eccentric coupling drive, a compensatory mass is provided, which is disposed outside of the transmission housing.

The invention relates to a power-driven hand tool, comprising a tool spindle that can be driven in a rotational oscillatory manner about its longitudinal axis and that is designed to carry a tool, and comprising a transmission housing, in which there is carried an eccentric coupling drive for driving the tool spindle and from which the tool spindle projects outwardly with one end.
Such a hand tool is known from WO 2008/128804 A1. The tool in that case is a power tool having a drive unit, for driving a drive shaft, and having an output shaft, on which a tool is carried. The rotary motion of the drive shaft can be transferred to the output shaft via an eccentric coupling device.
Such hand tools provided with an oscillatory drive can be used, for instance, to cut or grind workpieces, the oscillatory motion of the tool making it possible, in principle, to achieve precise guidance with a high cutting and material removal rate.
It has been found that, during use of such hand power tools, vibrations can occur that a user may perceive as irritating in the case of prolonged use.
In this connection, for the purpose of vibration compensation, WO 2008/128804 A1 proposes a mass compensation device, which executes a compensatory motion counteracting the oscillatory motion generated by the oscillatory drive.
In principle, therefore, it is possible to reduce vibrations, but the mass compensation device necessitates a more elaborate structure and a considerable additional weight. In addition, the mass compensation device requires a whole series of parts that are movably coupled to one another and that have to be supplied with transmission grease in order to ensure that the machine runs smoothly. Since the oscillatory drive concerned is usually operated at high frequency, this results in flexing motions and grease stresses being produced, which can result in heating of the tool and which can have a detrimental effect upon the efficiency and service life of the machine concerned.


Disclosed herein are immunogenic compositions for producing immediate and sustained immunity to infectious viral and bacteriological pathogens. A univalent immunogenic composition is disclosed comprising an isolated antigen and a polynucleotide formulated into a nanoparticle or liposome. Furthermore, multivalent immunogenic compositions are disclosed comprising multiple univalent immunogenic compositions. Also disclosed, are methods of inducing protective or therapeutic immune responses in individuals comprising administering one or more univalent immunogenic compositions.

Every year many people catch "the flu" and for most it is a self-limiting illness with recovery occurring between two to three weeks. Influenza is however, a potentially more severe infectious disease which is highly contagious. It is estimated that there are between three to five million cases of severe flu worldwide resulting in up to 500,000 deaths annually. There are two types of influenza viruses that cause epidemic human disease: the Influenza A virus which has many different strains, and the Influenza B virus which consists of a single strain. Current flu vaccines are a mixture of viral antigens prepared from selected strains of influenza A virus and from the single strain of the influenza B virus. The current vaccination programs are aimed at containing the seasonal flu. Health authorities from many countries collaborate with one another to predict the strain of influenza A virus that is likely to cause flu in the upcoming months. For the most part, these types of vaccination programs have worked well to contain the seasonal flu, although they become less effective when the flu epidemic is caused by a different influenza A strain than was predicted. This is because vaccination against one influenza A strain affords little if any immunity against a different influenza A strain. Once the strain is identified it takes about six months to manufacture large quantities of the appropriate vaccine. As such, one of the drawbacks of these vaccination programs is the time it takes to formulate a vaccine which may not even provide any protection against the influenza A strain causing seasonal flu in a particular season. For instance, if it takes six months to formulate a vaccine which provides little or no immunity because the predicted strain is not the one causing the infection, it will take another six months to develop the appropriate vaccine at which point there may be a threat for a major flu pandemic.
It would therefore be desirable to develop an effective immunogenic composition that is tailored to any flu strain that may arise and that can be produced in large quantities and deployed rapidly. Further, it would be desirable if the immunogenic composition could elicit an immediate and prolonged immunity to the flu virus.
The desirability of developing such an immunogenic composition becomes even more urgent when one considers that every ten to twenty years a flu strain arises that infects a large proportion of the world's population and has the potential to kill tens of millions of people. For example, within the last century there have been three major flu pandemics: the Spanish Flu in 1918-1920 which killed 40 million to 100 million people; the Asian Flu in 1957-1958 which killed 1 million to 1.5 million people; and the Hong Kong Flu in 1968-1969 which killed about 1 million people.
Another major obstacle in developing an effective vaccination program is that the influenza A virus is constantly changing. For example, it is known that the influenza A virus may undergo successive point mutations during replication (i.e. genetic drift) and can gradually acquire the capacity over time to become more virulent. Another way in which new strains of flu virus appear is when different flu strains may co-infect a host and exchange genetic information with each other (i.e. genetic shift) resulting in the appearance of a new flu strain with different infective properties and pathogenic potential from either of its parent strains.
Different strains of the influenza A virus are known to infect a variety of animal species, including birds and pigs, and some of these strains may cross specie lines and infect humans. If the infected human also happens to be co-infected with another strain of influenza virus there is a possibility that the two viral strains may exchange genetic information resulting in the appearance of a new strain. For example, there is great concern that the avian flu virus found in domestic and wild birds may infect a human who is carrying a human flu virus strain and exchange genetic information to form a new flu viral strain with the capacity to propagate from human to human resulting in a worldwide pandemic.
There are intensive efforts being made to develop antiviral drugs and vaccines to combat the threat of a worldwide pandemic. Much of the research on flu vaccine is based on traditional methods of growing the virus in embryonated eggs or in tissue cultured cells and then extracting the viral proteins to prepare a vaccine. This has worked fairly well for seasonal flu vaccines where health agencies are able to identify new strains of flu virus as they arise and have sufficient time to prepare the appropriate vaccine. However, the vaccination program still has to be repeated each year as immunity to one strain of the flu virus will not fully protect against any new strain that develops.
Another major obstacle with the traditional vaccination program is that because of mass transit and the large numbers of air travelers, any flu strain that arises in one country can quickly spread among other countries and infect the general population. Moreover, because of the many potential permutations of influenza virus strains that can arise, it is difficult to prepare a vaccine in a timely fashion using the traditional method of growing the virus in embryonated eggs or culturing viral infected cells. Thus, the time frame for identifying new viral strains and preparing large amounts of the correct vaccine has grown increasingly short which continues to be one of the major hindrances facing the traditional vaccination program. There are also very stringent manufacturing safety protocols that must be employed throughout production when a pathogenic virus is used to prepare a vaccine. Even the more recent methods of using genetic engineering to prepare recombinant viral antigens still require several months to prepare a suitable vaccine that may not be deployed in time to be effective.
The current vaccination programs that were developed for the seasonal flu are unable to produce the large quantities of vaccine in the limited time available to protect against a flu pandemic. Even the most current vaccine production methods using cell culture requires about 4 months to produce the appropriate vaccine (Novartis 2008). This time frame is clearly inadequate when the response time required to prevent a flu pandemic is measured in days.
The difficulty is further compounded because the current vaccines are only designed to elicit a classical immune response which can take several weeks to develop after vaccination. Moreover, to develop full immunity two doses of vaccine are often required. For example, The World Health Organization reported in 2007 that "It is unlikely that a potential pandemic could be successfully contained through the use of vaccination alone. Vaccination, with some exceptions, is not normally used to "contain" outbreaks of seasonal influenza. Full immunity is likely to require two doses of vaccine, and to take 3 weeks to develop after the first vaccination. Moreover, the degree of antigenic match between stockpiled vaccine and a potential H5N1 influenza pandemic virus cannot be known. There will also be considerable logistical challenges in vaccinating large numbers (possibly millions) of people over a relatively short period of time."
In view of the deficiencies of the current vaccination programs it would be desirable to develop an immunogenic composition that could provide immediate and long-term immunity to any flu strain that should arise. It would also be desirable to be able to produce large quantities of the appropriate flu immunogenic composition very quickly so that it can be deployed in time to be effective.


A snowboard binding is provided for releasably connecting a boot to a snowboard. One embodiment of the invention includes inner and outer main bodies to receive a two-piece cleat. A second embodiment includes inner and outer hooks for hooking, and a latch for securing, a one-piece cleat. A third embodiment includes a front main body and a spring-loaded latch in a rear main body for engaging a one-piece cleat. A fourth embodiment engages a one-piece cleat with inwardly beveled, semi-circular inner and outer main bodies. A fifth embodiment engages a one-piece cleat with a front main body and a latch, fixedly mounted upon an axle, within a rear main body. The latch is biased toward the engaged position by a spring. In a sixth embodiment of the invention, a one-piece cleat is engaged with a front main body and two rear spring biased latches. In a seventh embodiment, among other things, the cleat is formed in two pieces.

The present invention relates generally to a snowboard binding. More specifically, the present invention relates to a binding mechanism affixed to a snowboard and a cleat affixed to a boot with the cleat being releasably engaged by the binding mechanism.
In the sport of snowboarding, a rider rides the snowboard down a snow covered hill. The snowboard is shaped generally like a small surfboard or a large skateboard without wheels. The rider stands with his feet generally transverse to the longitudinal axis of the snowboard. It is necessary to provide means to secure the rider's boots to the snowboard.
It is desirable to have a manual release for the snowboard binding that is easy for the rider to operate. This is advantageous when the rider wishes to dismount from the board and walk on the terrain, or when he wishes to release one foot and push himself a short distance on snow while the other foot is bound to the snowboard, or when the rider wants to disengage the binding to get on or off a lift. Therefore, it is desirable to have a snowboard binding which securely holds the boots to the snowboard, does not release when the rider falls, but is easy to manually release.
When the rider does walk in the snow, it is common for snow to be caked to the sole of the rider's snowboard boots. This interferes with remounting the boot onto the snowboard because snow becomes trapped between the sole of the boot and the top surface of the snowboard and in the binding mechanism itself, making it difficult to close and latch the mechanism. It is therefore desirable to have a boot and cleat design which is not prone to having snow stick to it. It is also desirable to have a cleat and binding design which operates despite the presence of snow on the cleat, the sole of the boot, or the top surface of the snowboard.
Since a rider may find himself on uneven terrain when he needs to engage his boots into the binding, it is also desirable to have a binding mechanism which operates with an easy step-in motion. Such a binding mechanism should make it easy to place the boot in the proper location relative to the binding and to engage the cleat with the binding by the step-in motion.
To provide secure engagement of the boot against the snowboard, it is desirable that the attachment points of the cleat be far apart from one another. This will securely hold the boot in place during riding and help prevent lift up of the heel during maneuvering. However, a large cleat makes it cumbersome to walk as it is prone to knocking against the rider's legs as he walks and also increases the stiffness of the sole of the boot making it more difficult to walk. There is therefore a need for a binding and cleat design which provides adequate binding strength, yet still allows the snowboard rider to walk easily when the boot is disengaged from the binding.
As a rider is using the snowboard, he may traverse rough terrain. If the cleat is mounted directly on the top surface of the snowboard, this increases the transmission of vibration through the snowboard into the rider's foot making riding uncomfortable. It is therefore desirable to have a cleat and binding design which absorbs vibration from the terrain which is transmitted through the snowboard.
A snowboard binding generally orients the rider's boots a fixed distance apart and transverse to the longitudinal axis of the snowboard. This can be uncomfortable for some riders. It is therefore desirable to have a binding mechanism and cleat design which allows for easy adjustment of the angular orientation of the boots relative to the longitudinal axis of the snowboard and also allows for adjustment of the spacing of the boots relative to one another.
Snowboard binding mechanisms are disclosed in U.S. Pat. No. 5,299,823 (Glaser), U.S. Pat. No. 5,236,216 (Ratzek), U.S. Pat. No. 5,145,202 (Miller), U.S. Pat. No. 4,973,073 (Raines), U.S. Pat. No. 4,728,116 (Hill), U.S. Pat. No. 3,900,204 (Weber), and U.S. Reissue Pat. No. Re. 33,544. U.S. Pat. No. 4,571,858 (Faulin) discloses a shoe sole for a ski binding.


According to one embodiment, an electronic apparatus includes a main body deformable in a flat state and a bent state, and a spring structure which is provided on the main body and keeps the main body in the flat state or the bent state. The main body includes an elastic member, and first and second rigid members. The spring structure includes a plate spring which extends in a direction of crossing the elastic member, and is supported by the first and the second rigid members on both ends of the plate spring.

As an electronic apparatus, a tablet terminal (a tablet-type portable computer) provided with a sheet-like flexible display (sheet display) whose display screen is flexibly deformable, for example, is known.
Such a tablet terminal is required to have both sufficient rigidity to keep the sheet display in a flat state, and optimal flexibility to bend the sheet display.


A groomer for turf surfaces includes a groomer frame that mounts a first style of grooming brush for use on an artificial turf surface and a second style of grooming brush for use on a natural turf surface. The first style of grooming brush comprises a brush formed by spaced brush walls with each brush wall having a substantially single row of brush bristles with no bristles being placed between the brush walls. The second style of grooming brush is that similar to a push broom where the brush bristles are packed across the width of the brush head. When configured for artificial turf surfaces, a front row of scarifying spring tines helps the trailing brushes to level out the infill material and the attitude of the groomer frame can be tilted tail down to put more downpressure on the infill material. A debris remover attached to the rear of the frame can pick up and hold metallic debris that is often found in the turf surface.

Turf surfaces are commonly used as the playing surfaces for athletic or recreational activities, such as golf courses, football fields, baseball fields, and the like. Traditionally, turf surfaces at these venues comprised natural turf surfaces in which the soil or dirt of the ground had an upper layer of grass growing out of the soil or dirt. Obviously, such natural turf surfaces were restricted to outdoor environments, had to have adequate amounts of sunshine and water in order to keep the grass alive, and the grassy top layer had to be periodically cut or mowed to keep the height of the grass at a desired level. Accordingly, the costs to maintain a natural turf surface could be fairly substantial.
In more recent years, artificial turf surfaces have been developed that more closely resemble the look and feel of natural turf surfaces than early versions of artificial turf surfaces. These more recent artificial turf surfaces comprise a backing material that is laid atop the ground with the backing material having upstanding ribbons of artificial fibers that resemble blades of grass. In addition, such turf surfaces have one or more layers of particulate material placed atop the backing material and spread out over the backing material to surround the grass like fibers. The layers of particulate material can comprise a bottom layer of intermixed hard sand particles and resilient rubber granules and a top layer of resilient rubber granules as disclosed in U.S. Pat. No. 7,306,838. One brand of such an artificial turf surface that is available today is FieldTurf.
Turf surfaces, whether natural or artificial, have different grooming needs to keep them looking and playing their best. For example, a natural turf surface is often treated with a particulate top dressing material that must be spread or leveled out evenly in order to be most effective. In the morning, a natural turf surface is often heavily laden with dew. After mowing, a natural turf surface might be littered with clumps of grass clippings. It has been known in the art to pull a groomer across a natural turf surface to address these various needs, the groomer having a plurality of brushes that smooth the natural turf surface to smooth out top dressing material, to remove dew, or to smooth out and hide the grass clippings in the uncut grass. U.S. Pat. No. 6,655,469 shows a known prior art groomer.
Artificial turf surfaces also need to be groomed, but for somewhat different reasons. There obviously will never be any grass clippings lying atop such a turf surface. But, the layers of particulate material in the artificial turf surface, which layers will be collectively referred to herein as the infill material, can and do get disturbed or redistributed by the action of those who are playing or moving on the turf surface. Thus, the infill material over time gets redistributed into high spots and low spots. When this happens, it would be desirable in such turf surfaces to level out the infill material so that it has a more uniform depth across the extent of the turf surface.
Various attempts have been made to groom artificial turf surfaces using the same types of groomers that have been used for natural turf surfaces. Basically, the same types of brushes and spring tines that are towed over natural turf surfaces have been towed over artificial turf surfaces. For example, GreensGroomer Worldwide, Inc., the assignee of the '469 patent referred to above, sells a groomer for use on natural turf surfaces that has a brush and spring tine design substantially the same as the groomer that is sold for use on artificial turf surfaces.
However, the Applicants herein have discovered that substantially better results can be obtained when grooming artificial turf surfaces if a different style of brush and a different arrangement of spring tines are used. In addition, the Applicants have provided a single groomer that is convertible between use on natural turf surfaces and use on artificial turf surfaces so that duplicate pieces of equipment are not needed. Accordingly, the groomer disclosed and claimed in this application is a further advance in the art relating to the grooming of turf surfaces.

Turf groomer for natural and artificial turf surfaces


A device and method are for separating at least one optical fiber. A swivelled element and an asymmetric anvil are used so that a section of the fiber is contacted only in two positions that are substantially insignificant for the tensile strength of a spliced fiber. In one position, the glass fiber core of the section of the fiber is protected from damages by a fiber sheathing. In the other position that is contiguous to the position of separation, mechanical damages are of minor importance since they are at least partially repaired by the heat produced during splicing.

In the age of modern communication and information technology, optical data transmission by way of glass fiber cables plays a critical role. The design of reliable optical networks is dependent on the capability to cut glass fiber cables, which are also referred to in the following text as optical fibers or optical waveguides, such that a defined end surface, in particular an end surface which is as planar as possible, is produced at the end of the cut glass fiber cables. Planar end surfaces are required, for example, for splicing, that is to say thermal connection of two glass fiber cables to form a new, longer glass fiber cable, when the spliced joint is intended to result in the optical losses being as low as possible. Planar end surfaces are likewise required for low-loss optical coupling between an optical fiber and an optical connector or an optical coupling.
Optical fibers are generally cut by positioning the glass fiber at the point to be cut parallel over an anvil in an apparatus for cutting optical fibers, and by scoring it at right angles to the glass fiber. This can be done by using a scoring apparatus. When the optical fiber is subsequently bent, it preferably breaks at the scoring point. High-quality cutting apparatuses for glass fibers are in consequence distinguished in that the broken surface, which runs at right angles to the glass fiber axis, is as planar as possible, and in that the broken surface quality is subject to as few fluctuations as possible over a large number of cutting processes.
DE 33 17 304 A1 discloses an apparatus for cutting optical waveguides, which allows a high broken surface quality to be achieved, that is to say the broken surfaces of cut glass fibers are essentially free of disturbing notches, scratches and other uneven features. The high broken surface quality is achieved by providing a slot in an anvil, thus producing a symmetrical stress distribution in the cross section of the glass fiber at the scoring point. In this case, the width of the slot is governed by the diameter of the fiber to be cut.
DE 33 22 127 A1 discloses a method and an apparatus for cutting optical waveguides, in which the optical waveguide to be cut is held firmly with the aid of two clamping devices, is prestressed over an anvil in the axial direction with the aid of a tensioning device, and is scored transversely axially at the cutting point on the anvil with the aid of a scoring device. Manual intervention during the operation of the cutting apparatus is largely precluded, in order to ensure that the quality of the broken surfaces that are produced during the cutting process is uniformly high. This is achieved by way of a common operating element, by which the scoring device, the clamping devices and the tensioning device are each moved against a spring force to a position such that the clamping devices, tensioning device and the scoring device are operated autonomously and successively after the insertion of the optical waveguide to be cut and when the load on the operating element is removed.
Furthermore, WO 99/47954 discloses a cutting apparatus for optical fibers, which has a control device, which can be operated manually, as well as functional elements for successive clamping, scoring and breaking of the fibers.
All the functional elements are operated by way of the control device. Transmission elements and spring elements are provided between the, control device and the functional elements, and allow the functional elements to be moved in a defined sequence as a function of the forward and return movement of the control device.
EP 0 528 636 A1 discloses an apparatus both for cutting and for splicing optical waveguides, in which, after a cutting process, the optical waveguides to be spliced can be transferred by means of a transfer apparatus, which can pivot, from the cutting apparatus in the correct orientation to the splicing apparatus.
U.S. Pat. No. 4,463,886, DE 29 19 121 and U.S. Pat. No. 6,122,936 each disclose cutting apparatuses for optical waveguides, in which the optical waveguides are slightly curved before the scoring process. As a result of the mechanical stress which is caused in the optical waveguide by the bending process, the optical waveguide is broken by the scoring process, resulting in a largely planar optical waveguide end surface.
The known cutting apparatuses for optical fibers have the disadvantage that the fiber is inserted into the cutting apparatus manually, so that there is a risk of the cylindrical outer surface of the cylindrical fiber being mechanically damaged, particularly in the vicinity of the cutting point. This thus considerably reduces the tensile strength of the spliced glass fibers.

Device and method for separating at least one optical fiber


A method for making a pressure sensor including the steps of providing a substrate and forming or locating a pressure sensing component on the substrate. The method further includes the step of, after the forming or locating step, etching a cavity in the substrate below the pressure sensing component to define a diaphragm above the cavity with the pressure sensing component located on the diaphragm. The pressure sensing component includes an electrically conductive electron gas which changes its electrical resistance thereacross upon movement of the diaphragm.

Pressure sensors are widely used to sense the pressure of various fluids. Many existing pressure sensors utilize a flexible diaphragm having a piezoresistor located thereon such that flexure of the diaphragm causes a change in the resistance of the piezoresistor. However, many piezoresistive materials are unable to withstand high temperatures. The limited temperature range of such piezoresistive materials limits the environments in which the pressure sensor can be used and also limits the processing or manufacturing steps (i.e. when manufacturing the sensor) which may take place after the piezoresistive materials are deposited. Accordingly, there is a need for a pressure sensor utilizing improved, heat resistant sensing materials.


The present invention provides a protein having an A chain of a ricin-like toxin, a B chain of a ricin-like toxin and a heterologous linker amino acid sequence, linking the A and B chains. The linker sequence contains a cleavage recognition site for a disease specific protease such as a cancer, inflammatory, fungal, viral or parasitic protease. The invention also relates to a nucleic acid molecule encoding the protein and to expression vectors incorporating the nucleic acid molecule. In addition, the invention relates to a method for producing the recombinant protein in yeast, to nucleic acid molecules for use in yeast and to yeast transformed with such nucleic acid molecules. Also provided is a method of inhibiting or destroying mammalian cancer cells, inflammatory cells, cells infected with a virus, a fugus, or parasite, or parasites utilizing the nucleic acid molecules and proteins of the invention and pharmaceutical compositions for treating human cancer, inflammatory disease, viral infection, fugal infection, or parasitic infection.

Bacteria and plants are known to produce cytotoxic proteins which may consist of one, two or several polypeptides or subunits. Those proteins having a single subunit may be loosely classified as Type I proteins. Many of the cytotoxins which have evolved two subunit structures are referred to as type II proteins (Saelinger, C. B. in Trafficking of Bacterial Toxins (eds. Saelinger, C. B.) 1-13 (CRC Press Inc., Boca Raton, Fla., 1990). One subunit, the A chain, possesses the toxic activity whereas the second subunit, the B chain, binds cell surfaces and mediates entry of the toxin into a target cell. A subset of these toxins kill target cells by inhibiting protein biosynthesis. For example, bacterial toxins such as diphtheria toxin or Pseudomonas exotoxin inhibit protein synthesis by inactivating elongation factor 2. Plant toxins such as ricin, abrin, and bacterial toxin Shiga toxin, inhibit protein synthesis by directly inactivating the ribosomes (Olsnes, S. & Phil, A. in Molecular action of toxins and viruses (eds. Cohen, P. & vanHeyningen, S.) 51-105 Elsevier Biomedical Press, Amsterdam, 1982).
Ricin, derived from the seeds of Ricinus communis (castor oil plant), may be the most potent of the plant toxins. It is estimated that a single ricin A chain is able to inactivate ribosomes at a rate of 1500 ribosomes/minute. Consequently, a single molecule of ricin is enough to kill a cell (Olsnes, S. & Phil, A. in Molecular action of toxins and viruses (eds. Cohen, P. & vanHeyningen, S.) (Elsevier Biomedical Press, Amsterdam, 1982). The ricin toxin is a glycosylated heterodimer consisting of A and B chains with molecular masses of 30,625 Da and 31,431 Da linked by a disulphide bond. The A chain of ricin has an N-glycosidase activity and catalyzes the excision of a specific adenine residue from the 28S rRNA of eukaryotic ribosomes (Endo, Y. & Tsurugi, K. J., Biol. Chem. 262:8128 (1987)). The B chain of ricin, although not toxic in itself, promotes the toxicity of the A chain by binding to galactose residues on the surface of eukaryotic cells and stimulating receptor-mediated endocytosis of the toxin molecule (Simmons et al., Biol. Chem. 261:7912 (1986)). Once the toxin molecule consisting of the A and B chains is internalized into the cell via clathrin-dependent or independent mechanisms, the greater reduction potential within the cell induces a release of the active A chain, eliciting its inhibitory effect on protein synthesis and its cytotoxicity (Emmanuel, F. et al., Anal. Biochem. 173: 134-141 (1988); Blum, J. S. et al., J. Biol. Chem. 266: 22091-22095 (1991); Fiani, M. L. et al., Arch. Biochem. Biophys. 307: 225-230 (1993)). Empirical evidence suggests that activated toxin (e.g. ricin, shiga toxin and others) in the endosomes is transcytosed through the trans-Golgi network to the endoplasmic reticulum by retrograde transport before the A chain is translocated into the cytoplasm to elicit its action (Sandvig, K. & van Deurs, B., FEBS Lett. 346: 99-102 (1994).
Protein toxins are initially produced in an inactive, precursor form. Ricin is initially produced as a single polypeptide (preproricin) with a 35 amino acid N-terminal presequence and 12 amino acid linker between the A and B chains. The pre-sequence is removed during translocation of the ricin precursor into the endoplasmic reticulum (Lord, J. M., Eur. J. Biochem. 146:403-409 (1985) and Lord, J. M., Eur. J. Biochem. 146:411-416 (1985)). The proricin is then translocated into specialized organelles called protein bodies where a plant protease cleaves the protein at a linker region between the A and B chains (Lord, J. M. et al., FASAB Journal 8:201-208 (1994)). The two chains, however, remain covalently attached by an interchain disulfide bond (cysteine 259 in the A chain to cysteine 4 in the B chain) and mature disulfide linked ricin is stored in protein bodies inside the plant cells. The A chain is inactive in proricin (O'Hare, M. et al., FEBS Lett. 273:200-204 (1990)) and it is inactive in the disulfide-linked mature ricin (Richardson, P. T. et al., FEBS Lett. 255:15-20 (1989)). The ribosomes of the castor bean plant are themselves susceptible to inactivation by ricin A chain; however, as there is no cell surface galactose to permit B chain recognition the A chain cannot re-enter the cell. The exact mechanism of A chain release and activation in target cell cytoplasm is not known (Lord, J. M. et al., FASAB Journal 8:201-208 (1994)). However, it is known that for activation to take place the disulfide bond between the A and B chains must be reduced and, hence, the linkage between subunits broken.
Diphtheria toxin is produced by Corynebacterium diphtheriae as a 535 amino acid polypeptide with a molecular weight of approximately 58 kD (Greenfield, L. et al., Proc. Natl. Acad. Sci. USA 80:6853-6857 (1983); Pastan, I. et al., Annu. Rev. Biochem. 61:331-354 (1992); Collier, R. J. & Kandel, J., J. Biol. Chem. 246:1496-1503 (1971)). It is secreted as a single-chain polypeptide consisting of 2 functional domains. Similar to proricin, the N-terminal domain (A-chain) contains the cytotoxic moiety whereas the C-terminal domain (B-chain) is responsible for binding to the cells and facilitates toxin endocytosis. Conversely, the mechanism of cytotoxicity for diphtheria toxin is based on ADP-ribosylation of EF-2 thereby blocking protein synthesis and producing cell death. The 2 functional domains in diphtheria toxin are linked by an arginine-rich peptide sequence as well as a disulphide bond. Once the diphtheria toxin is internalized into the cell, the arginine-rich peptide linker is cleaved by trypsin-like enzymes and the disulphide bond (Cys 186-201) is reduced. The cytotoxic domain is subsequently translocated into the cytosol substantially as described above for ricin and elicits ribosomal inhibition and cytotoxicity.
Pseudomonas exotoxin is also a 66 kD single-chain toxin protein secreted by Pseudomonas aeruginosa with a similar mechanism of cytotoxicity to that of diphtheria toxin (Pastan, I. et al., Annu. Rev. Biochem. 61:331-354 (1992); Ogata, M. et al., J. Biol. Chem. 267:25396-25401 (1992); Vagil, M. L. et al., Infect. Immunol. 16:353-361 (1977)). Pseudomonas exotoxin consists of 3 conjoint functional domains. The first domain Ia (amino acids 1-252) is responsible for cell binding and toxin endocytosis, a second domain II (amino acids 253-364) is responsible for toxin translocation from the endocytic vesicle to the cytosol, and a third domain III (amino acids 400-613) is responsible for protein synthesis inhibition and cytotoxicity. After Pseudomonas exotoxin enters the cell, the liberation of the cytotoxic domain is effected by both proteolytic cleavage of a polypeptide sequence in the second domain (near Arg 279) and the reduction of the disulphide bond (Cys 265-287) in the endocytic vesicles. In essence, the overall pathway to cytotoxicity is analogous to diphtheria toxin with the exception that the toxin translocation domain in Pseudomonas exotoxin is structurally distinct.
Class 2 ribosomal inhibitory proteins (RIP-2) constitute other toxins possessing distinct functional domains for cytotoxicity and cell binding/toxin translocation which include abrin, modeccin, volkensin, (Sandvig, K. et al., Biochem. Soc. Trans. 21:707-711 (1993)) and mistle toe lectin (viscumin) (Olsnes, S. & Phil, A. in Molecular action of toxins and viruses (eds. Cohen, P. & vanHeyningen, S.) 51-105 Elsevier Biomedical Press, Amsterdam, 1982; and Fodstad, et al. Canc. Res. 44:862 (1984)). Some toxins such as Shiga toxin and cholera toxin also have multiple polypeptide chains responsible for receptor binding and endocytosis.
The ricin gene has been cloned and sequenced, and the X-ray crystal structures of the A and B chains have been described (Rutenber, E. et al. Proteins 10:240-250 (1991); Weston et al., Mol. Bio. 244:410-422, 1994; Lamb and Lord, Eur. J. Biochem. 14:265 (1985); Halling, K. et al. Nucleic Acids Res. 13:8019 (1985)). Similarly, the genes for diptheria toxin and Pseudomonas exotoxin have been cloned and sequenced, and the 3-dimensional structures of the toxin proteins have been elucidated and described (Columblatti, M. et al., J. Biol. Chem. 261:3030-3035 (1986); Allured, V. S. et al., Proc. Natl. Acad. Sci. USA 83:1320-1324 (1986); Gray, G. L. et al., Proc. Natl. Acad. Sci. USA 81:2645-2649 (1984); Greenfield, L. et al., Proc. Natl. Acad. Sci. USA 80:6853-6857 (1983); Collier, R. J. et al., J. Biol. Chem. 257:5283-5285 (1982)).
The potential of bacterial and plant toxins for inhibiting mammalian retroviruses, particularly acquired immunodeficiency syndrome (AIDS), has been investigated. Bacterial toxins such as Pseudomonas exotoxin-A and subunit A of diphtheria toxin; dual chain ribosomal inhibitory plant toxins such as ricin, and single chain ribosomal inhibitory proteins such as trichosanthin and pokeweed antiviral protein have been used for the elimination of HIV infected cells (Olson et al., AIDS Res. and Human Retroviruses 7:1025-1030 (1991)). The high toxicity of these toxins for mammalian cells, combined with a lack of specificity of action poses a major problem to the development of pharmaceuticals incorporating the toxins, such as immunotoxins.
Due to their extreme toxicity there has been much interest in making ricin-based immunotoxins as therapeutic agents for specifically destroying or inhibiting infected or tumourous cells or tissues (Vitetta et al., Science 238:1098-1104(1987)). An immunotoxin is a conjugate of a specific cell binding component, such as a monoclonal antibody or growth factor and the toxin in which the two protein components are covalently linked. Generally, the components are chemically coupled. However, the linkage may also be a peptide or disulfide bond. The antibody directs the toxin to cell types presenting a specific antigen thereby providing a specificity of action not possible with the natural toxin. Immunotoxins have been made both with the entire ricin molecule (i.e. both chains) and with the ricin A chain alone (Spooner et al., Mol. Immunol. 31:117-125, (1994)).
Immunotoxins made with the ricin dimer (IT-Rs) are more potent toxins than those made with only the A chain (IT-As). The increased toxicity of IT-Rs is thought to be attributed to the dual role of the B chains in binding to the cell surface and in translocating the A chain to the cytosolic compartment of the target cell (Vitetta et al., Science 238:1098-1104 (1987); Vitetta & Thorpe, Seminars in Cell Biology 2:47-58 (1991)). However, the presence of the B chain in these conjugates also promotes the entry of the immunotoxin into nontarget cells. Even small amounts of B chain may override the specificity of the cell-binding component as the B chain will bind nonspecifically to galactose associated with N-linked carbohydrates, which is present on most cells. IT-As are more specific and safer to use than IT-Rs. However, in the absence of the B chain the A chain has greatly reduced toxicity. Due to the reduced potency of IT-As as compared to IT-Rs, large doses of IT-As must be administered to patients. The large doses frequently cause immune responses and production of neutralizing antibodies in patients (Vitetta et al., Science 238:1098-1104 (1987)). IT-As and IT-Rs both suffer from reduced toxicity as the A chain is not released from the conjugate into the target cell cytoplasm.
A number of immunotoxins have been designed to recognize antigens on the surfaces of tumour cells and cells of the immune system (Pastan et al., Annals New York Academy of Sciences 758:345-353 (1995)). A major problem with the use of such immunotoxins is that the antibody component is its only targeting mechanism and the target antigen is often found on non-target cells (Vitetta et al., Immunology Today 14:252-259 (1993)). Also, the preparation of a suitable specific cell binding component may be problematic. For example, antigens specific for the target cell may not be available and many potential target cells and infective organisms can alter their antigenic make up rapidly to avoid immune recognition. In view of the extreme toxicity of proteins such as ricin, the lack of specificity of the immunotoxins may severely limit their usefulness as therapeutics for the treatment of cancer and infectious diseases.
The insertion of intramolecular protease cleavage sites between the cytotoxic and cell-binding components of a toxin can mimic the way that the natural toxin is activated. European patent application no. 466,222 describes the use of maize-derived pro-proteins which can be converted into active form by cleavage with extracellular blood enzymes such as factor Xa, thrombin or collagenase. Garred, O. et al. (J. Biol. Chem. 270:10817-10821 (1995)) documented the use of a ubiquitous calcium-dependent serine protease, furin, to activate shiga toxin by cleavage of the trypsin-sensitive linkage between the cytotoxic A-chain and the pentamer of cell-binding B-units. Westby et al. (Bioconjugate Chem. 3:375-381 (1992)) documented fusion proteins which have a specific cell binding component and proricin with a protease sensitive cleavage site specific for factor Xa within the linker sequence. O'Hare et al. (FEBS Lett. 273:200-204 (1990)) also described a recombinant fusion protein of RTA and staphylococcal protein A joined by a trypsin-sensitive cleavage site. In view of the ubiquitous nature of the extracellular proteases utilized in these approaches, such artificial activation of the toxin precursor or immunotoxin does not confer a mechanism for intracellular toxin activation and the problems of target specificity and adverse immunological reactions to the cell-binding component of the immunotoxin remain.
In a variation of the approach of insertion of intramolecular protease cleavage sites on proteins which combine a binding chain and a toxic chain, Leppla, S. H. et al. (Bacterial Protein Toxins zbl.bakt.suppl. 24:431-442 (1994)) suggest the replacement of the native cleavage site of the protective antigen (PA) produced by Bacillus anthracis with a cleavage site that is recognized by cells that contain a particular protease. PA, recognizes, binds, and thereby assists in the internalization of lethal factor (LF) and edema toxin (ET). also produced by Bacillus anthracis. However, this approach is wholly dependent on the availability of LF, or ET and PA all being localized to cells wherein the modified PA can be activated by the specific protease. It does not confer a mechanism for intracellular toxin activation and presents a problem of ensuring sufficient quantities of toxin for internalization in target cells.
The in vitro activation of a Staphylococcus-derived pore-forming toxin, α-hemolysin by extracellular tumour-associated proteases has been documented (Panchel, R. G. et al., Nature Biotechnology 14:852-857 (1996)). Artificial activation of α-hemolysin in vitro by said proteases was reported but the actual activity and utility of α-hemolysin in the destruction of target cells were not demonstrated.
Hemolysin does not inhibit protein synthesis but is a heptameric transmembrane pore which acts as a channel to allow leakage of molecules up to 3 kD thereby disrupting the ionic balances of the living cell. The α-hemolysin activation domain is likely located on the outside of the target cell (for activation by extracellular proteases). The triggering mechanism in the disclosed hemolysin precursor does not involve the intracellular proteolytic cleavage of 2 functionally distinct domains. Also, the proteases used for the α-hemolysin activation are ubitquitiously secreted extracellular proteases and toxin activation would not be confined to activation in the vicinity of diseased cells. Such widespread activation of the toxin does not confer target specificity and limits the usefulness of said α-hemolysin toxin as therapeutics due to systemic toxicity.
A variety of proteases specifically associated with malignancy, viral infections and parasitic infections have been identified and described. For example, cathepsin is a family of serine, cysteine or aspartic endopeptidases and exopeptidases which has been implicated to play a primary role in cancer metastasis (Schwartz, M. K., Clin. Chim. Acta 237:67-78 (1995); Spiess, E. et al., J. Histochem. Cytochem. 42:917-929 (1994); Scarborough, P. E. et al., Protein Sci. 2:264-276 (1993); Sloane, B. F. et al., Proc. Natl. Acad. Sci. USA 83:2483-2487 (1986); Mikkelsen, T. et al., J. Neurosurge 83:285-290 (1995)). Matrix metalloproteinases (MMPs or matrixins) are zinc-dependent proteinases consisting of collagenases, matrilysin, stromelysins, gelatinases and macrophage elastase (Krane, S. M., Ann. N.Y. Acad. Sci. 732:1-10 (1994); Woessner, J. F., Ann. N.Y. Acad. Sci. 732:11-21 (1994); Carvalho, K. et al., Biochem. Biophys. Res. Comm. 191:172-179 (1993); Nakano, A. et al. J. of Neurosurge, 83:298-307 (1995); Peng, K-W, et al. Human Gene Therapy, 8:729-738 (1997); More, D. H. et al. Gynaecologic Oncology, 65:78-82 (1997)). These proteases are involved in pathological matrix remodeling. Under normal physiological conditions, regulation of matrixin activity is effected at the level of gene expression. Enzymatic activity is also controlled stringently by tissue inhibitors of metalloproteinases (TIMPs) (Murphy, G. et al., Ann. N.Y. Acad. Sci. 732:31-41 (1994)). The expression of MMP genes is reported to be activated in inflammatory disorders (e.g. rheumatoid arthritis) and malignancy.
In malaria, parasitic serine and aspartic proteases are involved in host erythrocyte invasion by the Plasmodium parasite and in hemoglobin catabolism by intraerythrocytic malaria (O'Dea, K. P. et al., Mol. Biochem. Parasitol. 72:111-119 (1995); Blackman, M. J. et al., Mol. Biochem. Parasitol. 62:103-114 (1993); Cooper, J. A. et al., Mol. Biochem. Parasitol. 56:151-160 (1992); Goldberg, D. E. et al., J. Exp. Med. 173:961-969 (1991)). Schistosoma mansoni is also a pathogenic parasite which causes schistosomiasis or bilharzia. Elastinolytic proteinases have been associated specifically with the virulence of this particular parasite (McKerrow, J. H. et al., J. Biol. Chem. 260:3703-3707 (1985)).
Welch, A. R. et al. (Proc. Natl. Acad. Sci. USA 88:10797-10800 (1991)) has described a series of viral proteases which are specifically associated with human cytomegalovirus, human herpesviruses, Epstein-Barr virus, varicella zoster virus-I. and infectious laryngotracheitis virus. These proteases possess similar substrate specificity and play an integral role in viral scaffold protein restructuring in capsid assembly and virus maturation. Other viral proteases serving similar functions have also been documented for human T-cell leukemia virus (Blaha, I. et al., FEBS Lett. 309:389-393 (1992); Pettit, S. C. et al., J. Biol. Chem. 266:14539-14547 (1991)), hepatitis viruses (Hirowatari, Y. et al., Anal. Biochem. 225:113-120 (1995); Hirowatari, Y. et al., Arch. Virol. 133:349-356 (1993); Jewell, D. A. et al., Biochemistry 31:7862-7869 (1992)), poliomyelitis virus (Weidner, J. R. et al., Arch. Biochem. Biophys. 286:402-408 (1991)), and human rhinovirus (Long, A. C. et al., FEBS Lett. 258:75-78 (1989)).
Candida yeasts are dimorphic fungi which are responsible for a majority of opportunistic infections in AIDS patients (Holmberg, K. and Myer, R., Scand. J. Infect. Dis. 18:179-192 (1986)). Aspartic proteinases have been associated specifically with numerous virulent strains of Candida including Candida albican, Candida tropicalis, and Candida parapsilosis (Abad-Zapatero, C. et al., Protein Sci. 5:640-652 (1996); Cutfield, S. M. et al., Biochemistry 35:398-410 (1995); Ruchel, R. et al, Zentralbl. Bakteriol. Mikrobiol Hyg. I Abt. Orig. A. 255:537-548 (1983); Remold, H. et al., Biochim. Biophys. Acta 167:399-406 (1968)), and the levels of these enzymes have been correlated with the lethality of the strain (Schreiber, B, et al., Diagn. Microbiol. Infect. Dis. 3:1-5 (1985)).
The production of ricin-like toxins has been described for both bacterial cell (CA1,324,093, CA1,324,095) and insect cell cultures (WO89/01037) however each of these methods has significant disadvantages. Insect cell cultures (baculovirus) are poorly adapted to protein production on an industrial scale for a variety of reasons including: 1) the requirement for infection with baculovirus for efficient heterologous protein expression, making them unsuitable for continuous production; 2) the transient nature of the baculovirus infection makes the process difficult to validate and 3) the cost of culturing insect cells is often prohibitively expensive. Production of heterologous proteins in bacterial culture is more cost-effective and consistent, however cannot provide glycosylation. Furthermore, it has not been shown that active protoxins (A- and B-chains linked by a polypeptide) can be produced in bacteria at commercially useful levels.
It would therefore be desirable to have a convenient and economical method for producing biologically active glycosylated and non-glycosylated ricin-like toxins and protoxins. Such protein preparations should be readily purified to homogeneity, while retaining a high level of biological activity (as measured by lectin-binding ability and cytotoxicity assays).

This patent is subject to a terminal disclaimer.

Ricin-like toxin variants for treatment of cancer, viral or parasitic infections


An apparatus for relatively moving a probe facing an information carrier and recording information on and/or reproducing information from the information carrier with the probe provided with a detector for detecting an error in the probe.

1. Field of the Invention
The present invention relates to an apparatus for observing a surface of a material, finely machining the material and recording and reproducing information by a technique of a scanning tunneling microscope (STM) or the like.
2. Related Background Art
The observation, evaluation and fine machining of a semiconductor or high molecule material in the order of an atom or a molecule by using the STM technique (E. E. Ehrichs, 4th International Conference on Scanning Tunneling Microscopy/spectroscopy, '89, S13-3) and applications thereof to various fields such as a recorder have been studied.
Among others, a demand for a large capacity recorder for computer calculation information and image information is increasing more and more, and size reduction of the recorder is desired because of the fact that a size of a microprocessor has been reduced and a computing ability of the microprocessor has been improved. In order to meet the above requirements, a recording and reproducing apparatus has been proposed which records information on a recording area of 10 nm.sup.2 at minimum by applying a voltage from a transducer having a tunneling current generating probe mounted on drive means to finely adjust spacing to a recording medium in order to change a work function of a recording medium surface, and reads the information by detecting a change in a tunneling current due to the change in the work function.
The above transducer is very effective means for not only the recorder but also material evaluation and fine machining of a nanometer order.
In the above apparatus, it is necessary to adjust spacing between a probe and a medium so that processing is always performed at proper spacing. For example, in the recording and reproducing apparatus described above, if the drive means malfunctions to separate the probe from the medium more than required, the information cannot be written onto the recording medium. If a similar malfunction occurs in the information record mode, the information is not correctly read and all signals read from the recording medium may be "0". Such malfunction may occur not only in the spacing adjustment but also when the probe is scanned parallel to the medium surface. In the past, when such malfuction occurs, the written information is read by another apparatus for analysis or the read information is checked if it is not normal for a predetermined time period in order to detect the malfunction. Accordingly, a long time is taken to detect the error and it is time consuming.

Information recording/reproducing apparatus with STM cantilever probe having a strain gauge


A digital-to-analog converter (DAC) for a sigma-delta modulator is provided. The DAC has a switched capacitor structure using an operational amplifier (OP amp) and performs a function exceeding 3-level using a switching method employing only one capacitor in single ended form. Thus, DAC non-linearity caused by capacitor mismatching does not occur, and the number of output levels of the DAC is increased. Also, the DAC capacitor may be applied to a general DAC to increase the ratio of DAC output levels to capacitors.

1. Field of the Invention
The present invention relates to a sigma-delta modulator, and more particularly, to a multi-bit sigma-delta modulator and a digital-to-analog converter for a sigma-delta modulator that are capable of implementing a five-level output through one capacitor in single ended form. The digital-to-analog converter of the present invention may be extendible to a differential operation. Hereinafter, a configuration based single ended form will be described for convenience.
2. Discussion of Related Art
Generally, a sigma-delta modulator includes two blocks: an integrator for integrating a difference between an input analog signal and an output signal of a digital-to-analog converter (DAC) according to a code of an analog-to-digital converter (ADC), and the ADC for converting an analog output of the integrator into a digital signal.
FIG. 1A is a block diagram illustrating a general first-order sigma-delta modulator, and FIG. 1B illustrates the first-order sigma-delta modulator of FIG. 1A as a linear model.
As illustrated in FIGS. 1A and 1B, the general first-order sigma-delta modulator is configured with a negative feedback, and the ADC in the first-order sigma-delta modulator may be replaced with a model in which quantization noise is added. An output (Vout) that is the result of interpreting the general first-order sigma-delta modulator using the linear model of FIG. 1B is given by Formula 1.
[Formula 1]
      V                          out    =                    1                  s          +          1                          V                                      in        +                  s                  s          +          1                          e
As shown in Formula 1, the output (Vout) indicates a low-pass characteristic with respect to an input (Vin), and indicates a high-pass characteristic with respect to the quantization noise (e). Therefore, if a low pass filter is used to produce an output of the sigma-delta modulator, the output may have low quantization noise and, accordingly, a high signal-to-noise ratio (SNR).
The SNR of the sigma-delta modulator having the above-described characteristics is determined by the number of integrators (L), which may be indicated as an order of the modulator, the number of ADC bits, and an oversampling ratio, which is a ratio of sampling frequency range to signal frequency range. The maximum SNR is given by Formula 2.
[Formula 2]
      SNR              (      dB      )        =      1.76    +          20                                              log                          (                                    2              B                        -            1                    )                      +          10                                      log                                      M        +                  20        ·        L        ·        log                                            M        +          20                                      log                                                        2                            L                        +            1                                    π          L
As shown in Formula 2, to increase the SNR, the order, the number of ADC bits, or the oversampling ratio should be increased.
However, the method of increasing the order has a problem regarding stability, and reduces an available signal range. Also, since the method of increasing the oversampling ratio requires a high sampling frequency, a circuit should operate at high speed. Therefore, the above-mentioned methods are not suitable for the low-voltage, high-speed sigma-delta modulator.
Meanwhile, the number of ADC bits in the high-resolution, high-speed, and low voltage sigma-delta modulator may be increased. However, when the number of ADC bits is increased, the performance of the sigma-delta modulator may be affected by linear characteristics of the DAC in a negative feedback loop.
FIG. 2 illustrates an integrator in the form of a commonly used switched capacitor also performing a function of a B-bit DAC. In FIG. 2, mismatching of a DAC capacitor 10 directly affects DAC linear characteristics. Since the mismatching of capacitors 11 through 12 is determined by a process characteristic, there is a limit to improving the mismatching characteristic. Accordingly, the performance of the high-resolution, high-speed, and low voltage sigma-delta modulator may deteriorate due to the capacitor mismatching.
Therefore, to solve a problem regarding the DAC capacitor mismatching, various methods such as Random Averaging, Clocked Averaging (CLA), Individual Level Averaging (ILA), Data Weighted Averaging (DWA), etc., have been suggested. However, these methods require a lot of complex digital circuits, and under certain conditions the performance of the DAC may deteriorate.

Multi-bit sigma-delta modulator and digital-to-analog converter with one digital-to-analog capacitor

Electronics and Telecommunications Research Institute


The present invention aims to provide a light control material capable of optionally controlling the light transmittance in an arbitrary wavelength range among a wide wavelength range, and a light control film formed by using the light control material.

A light control material capable of controlling the light transmittance in a specific wavelength range has been utilized for controlling transmitted light or for controlling color by interrupting light of a specific wavelength, and applied in various fields including, for example, interior materials, construction materials, electronic parts, and the like. Furthermore, in these days, materials capable of controlling the light transmittance in the infrared range have attracted attention and a variety of investigations on such materials have been conducted.
As examples of the light control materials of this kind, Patent Document 1 and Patent Document 2 propose a light control material containing a suspension of light-polarizing particles and a polymer resin. In a light control body formed by using the light control material, the polarizing particles are disposed to form a translucent form in response to an electric field. However, this kind of light control material has a problem that it is not possible to optionally and easily control the light transmittance in an arbitrary wavelength range among a sufficiently wide wavelength range from the visible light range to the near-infrared range.
Patent Document 3 and Patent Document 4 disclose a heat ray shielding light control material which is characterized by that a polymer gel that changes its volume depending on temperatures is used, and that a colorant and an infrared absorbing material are included in the polymer gel. A light control body formed by using this kind of light control material can control the transmittance of heat rays (near-infrared rays) in response to temperature due to the behavior of the infrared absorbing material, and also the transmittance in the visible light range can be controlled by the colorant. However, this kind of light shielding material has a problem that it is not possible to optionally and easily control the light transmittance in an arbitrary wavelength range in a sufficiently wide wavelength range from the visible light range to the near-infrared range.
Patent Document 5 discloses an electrochromic thin film consisting of a niobium oxide, and describes that the electrochromic thin film shows an excellent light controlling property in a wide wavelength range. However, when an inorganic oxide of this kind is used as a light control material, complicated steps need to be carried out to produce a light control element, thus leaving a problem for practical application.
With respect to the light control material for controlling the light transmittance in the infrared range, for example, Patent Document 6 discloses a material containing a diimonium salt compound having an infrared absorption and a polyester; Patent Document 7 discloses a coating liquid containing a dioxadinaphthopentacene compound having an infrared absorption and a binder resin; and Patent Document 8 discloses a heat shielding coating material using an infrared-absorbing perylene based pigment. However, those light control materials have a problem in dispersibility of the infrared absorbing compound in a binder resin, and due to uneven dispersion, uniform absorption characteristics may not be easily achieved.
Patent Document 1: Japanese Kokai Publication No. 2005-105131
Patent Document 2: Japanese Kokai Publication No. 2002-214653
Patent Document 3: Japanese Kokai Publication No. 2002-155215
Patent Document 4: Japanese Kokai Publication No. 2002-082364
Patent Document 5: Japanese Kokai Publication No. Hei-9-227860
Patent Document 6: Japanese Kokai Publication No. 2001-174627
Patent Document 7: Japanese Kokai Publication No. 2002-139619
Patent Document 8: Japanese Kokai Publication No. 2005-076019

Light control material and light control film

National Institute of Advanced Industrial Science and Technology


A driving circuit for producing sustain waveforms of a plasma display panel (PDP) is mentioned. The driving circuit includes the functions of voltage clamping and energy recovery. By controlling switches contained in the driving circuit, the supplied voltage source can be made to be only half of the sustain voltage. The voltage stress of some components will therefore be lower. In addition, the numbers of components can be reduced in the driving circuit.

1. Field of the Invention
The present invention relates to a driving circuit, and more specifically, to a driving circuit for a plasma display panel (PDP).
2. Description of the Prior Art
In recent years, there has been an increasing demand for planar matrix displays such as plasma display panels (PDP), liquid-crystal displays (LCD) and electroluminescent displays (EL display) in place of cathode ray tube terminals (CRT) due to the advantage of the thin appearance of the planar matrix displays.
In a PDP display, a sustaining discharge pulse activates inert gas to generate ultraviolet so that the ultraviolet further activates fluorescent materials and visible light is emitted to display. As far as the PDP display is concerned, it is required to apply a high voltage to the electrodes. In particular, a pulse-duration of several microseconds is usually adopted. Hence the power consumption of the PDP display is quite considerable. Energy recovering (power saving) is therefore sought for. Many designs and patents have been developed for providing methods and apparatuses of energy recovering for PDPs. One of the examples is U.S. Pat. No. 5,828,353, "Drive Unit for Planar Display" by Kishi, et al., which is included herein by reference.
Please refer to FIG. 1. FIG. 1 is a block diagram of a prior art driving circuit 100. The plasma panel display can be taken as a panel equivalent capacitor Cp. The conventional driving circuit 100 includes four switches S1 to S4 for passing current, an X-side energy recovery circuit 110 and a Y-side energy recovery circuit 120 for charging/discharging the panel equivalent capacitor Cp from the X side of the panel equivalent capacitor Cp and the Y side of the panel equivalent capacitor Cp respectively. S5, S6, S7 and S8 are switches for passing current. D5, D6, D7 and D8 are diodes. V1 and V2 are two voltage sources. C1 and C2 are capacitors adopted for recovering energy, and L1 and L2 are resonant inductors. The X-side energy recovery circuit 110 includes an energy-forward channel comprising the switch S6, the diode D6 and the inductor L1, and an energy-backward channel comprising the inductor L1, the diode D5 and the switch S5. Similarly, the Y-side energy recovery circuit 120 also includes an energy-forward channel comprising the switch S8, the diode D8 and the inductor L2, and an energy-backward channel comprising the inductor L2, the diode D7 and the switch S7.
Please refer to FIG. 2. FIG. 2 is a flowchart of generating the sustaining pulses of the panel equivalent capacitor Cp of the PDP by the conventional driving circuit 100 illustrated in FIG. 1.
Step 200: Start;
Step 210: Keep the voltage potentials at the X side and the Y side of the panel equivalent capacitor Cp at ground by turning on the switches S3 and S4;
Step 220: Charge the X side of the panel equivalent capacitor Cp by the capacitor C1 and keep the voltage potential at the Y side of the panel equivalent capacitor Cp at ground by turning on the switches S6 and S4; wherein the voltage potential at the X side of the panel equivalent capacitor Cp goes up to V1 accordingly;
Step 230: Supply charge to the panel equivalent capacitor Cp of the PDP from the X side by turning on the switches S1 and S4; wherein the voltage potential at the X side of the panel equivalent capacitor Cp keeps at V1 and the voltage potential at the Y side of the panel equivalent capacitor Cp keeps at ground accordingly;
Step 240: Discharge the panel equivalent capacitor Cp from the X side and keep the voltage potential at the Y side of the panel equivalent capacitor Cp at ground by turning on the switches S5 and S4; wherein the voltage potential at the X side of the panel equivalent capacitor Cp goes down to ground accordingly;
Step 250: Keep the voltage potentials at the X side and the Y side of the panel equivalent capacitor Cp at ground by turning on the switches S3 and S4;
Step 260: Charge the Y side of the panel equivalent capacitor Cp by the capacitor C2 and keep the voltage potential at the X side of the panel equivalent capacitor Cp at ground by turning on the switches S8 and S3; wherein the voltage potential at the Y side of the panel equivalent capacitor Cp goes up to V2 accordingly;
Step 270: Supply charge to the panel equivalent capacitor Cp of the PDP from the Y side by turning on the switches S2 and S3; wherein the voltage potential at the Y side of the panel equivalent capacitor Cp keeps at V2 and the voltage potential at the X side of the panel equivalent capacitor Cp keeps at ground accordingly;
Step 280: Discharge the panel equivalent capacitor Cp from the Y side and keep the voltage potential at the X side of the panel equivalent capacitor Cp at ground by turning on the switches S7 and S3; wherein the voltage potential at the Y side of the panel equivalent capacitor Cp goes down to ground accordingly;
Step 290: Keep the voltage potentials at the X side and the Y side of the panel equivalent capacitor Cp at ground by turning on the switches S3 and S4;
Step 295: End.
Please refer to FIG. 3. FIG. 3 shows a diagram illustrating the voltage potentials at the X side and the Y side of the panel equivalent capacitor Cp, and the control signals, M1 to M8, of the switches S1 to S8 in FIG. 1 respectively. In FIG. 3, the horizontal axis represents the time, while the vertical axis represents the voltage potential. Note that the switches S1 to S8 are designed to close (turned on) for passing current when the control signal is high, and to open (turned off) such that no current can pass when the control signal is low.
Conventionally, the energy recovery (power saving) circuit provides two individual channels of charging and discharging the equivalent capacitor respectively (energy-forward channel and energy-backward channel) for each side of the panel equivalent capacitor Cp. Therefore, the amount of required components is quite large. Furthermore, the area of capacitors C1 and C2 is usually considerable. Hence the cost of energy recovery circuit is not easy to reduce.


An optical wavelength multiplexing apparatus is capable of controlling an attenuation amount of a variable optical attenuator at high speed, thereby preventing an optical level change generated by an upstream WDM section from flowing into a downstream WDM section.

1. Field of the Invention
The present invention generally relates to a wavelength multiplexing method, and an apparatus thereof, and especially relates to the wavelength multiplexing method of a WDM (Wavelength Division Multiplexing) optical transmission system, and the apparatus thereof.
2. Description of the Related Art
In WDM optical transmission systems, transmission characteristics are heavily reliant upon power and optical SNR (signal to noise ratio) of each of the wavelengths, serving as optical channels, which are multiplexed. For this reason, the power levels of all the wavelengths are required to be equal to each other. To achieve this, each wavelength is input into a variable optical attenuator (VAT), and the power levels of the input wavelengths are made equal to each other by attenuating the power (for example, patent reference 1 listed below is referred to).
FIG. 1 shows a block diagram of an example of a conventional wavelength multiplexing apparatus (WDM apparatus). In FIG. 1, wavelengths CH1 through CHn are supplied to variable optical attenuators 101 through 10n, respectively, and are multiplexed by a multiplexing unit (MUX) 12. The multiplexed wavelengths constitute an optical signal, which is amplified by a transmitting amplifier (AMP) 14, and is output to an optical transmission path.
A part of the optical signal output from the transmitting amplifier 14 is branched (split off) at an optical coupler 16, and the branched part of the optical signal is supplied to an optical monitor unit 18. The optical monitor unit 18 performs an optical spectrum analysis with an optical spectrum analyzer (SAU), calculates an attenuation amount to be provided by each of the variable optical attenuators 101 through 10n, and controls the variable optical attenuators 101 through 10n via a serial interface 19 such that the optical power levels of all the wavelengths become equal.
Patent Reference 1
Japanese Provisional Patent No. H9-261205.
The above-mentioned conventional method is mainly for a point-to-point system, among various configurations of WDM systems, as shown at (A) of FIG. 2, where an input wavelength is provided by a stable optical source, such as a transponder. For this reason, the conventional method poses certain problems in a WDM system that is configured differently, namely, in the case of an add/drop apparatus 20 wherein a wavelength (channel) is branched (dropped) and another wavelength is inserted (added) as shown at (B) of FIG. 2, and a cross connect apparatus 22 that performs an optical switching function in units of wavelengths as shown at (C) of FIG. 2.
One of the conventional problems (the first problem) is relative to feedback speed, which is a function of operational performances of the optical spectrum analyzer and the variable optical attenuators. The optical spectrum analyzer monitors all the wavelengths that are multiplexed. In a typical monitoring method, a part of the optical signal is branched, and used for monitoring. The branched part of the optical signal is input to a diffraction lattice so that each wavelength is separated. Then, signal strength of each wavelength is measured by a sweeping operation.
FIG. 3 shows a conventional feedback control method. At Step S10, all the wavelengths are monitored by the optical spectrum analyzer SAU on the left-hand side of FIG. 3. At Step S11, a required attenuation amount of each wavelength is calculated based on variation among the wavelength levels. At Step S12, the required attenuation amount is transmitted to the respective variable optical attenuators VAT of each wavelength via the serial interface. Then, with reference to the right-hand side of FIG. 3, the required attenuation amount is received by the respective VAT at Step S13, and the respective attenuation amount of the VAT is changed to the required attenuation amount at Step S14. Consequently, at Step S15, the output level of the VAT is changed, and the output level of the corresponding wavelength (channel) is changed.
As for the signal strength of each wavelength being measured, in order to obtain an accurate measurement under this conventional method, the interval between measurements is required to be longer than 100 ms. Further, the serial interface, which is normally used for transmitting the required attenuation amount of each wavelength to the respective variable optical attenuator from the optical spectrum analyzer, is required to handle a large number of wavelengths, which is of a magnitude of 100, and growing.
Even if the measurement speed of the optical spectrum analyzer is improved by simultaneously monitoring all the wavelengths, there is a limit to improvement of the transmission speed of the serial interface. For this reason, the feedback cycle cannot be raised to a desired high speed by the conventional method, wherein only the optical spectrum analyzer directly controls the required attenuation amount of the variable optical attenuators.
When the input level of an optical channel fluctuates, the conventional control method can respond to a slow change over a period longer than 100 ms, and such a slow change can be absorbed (dealt with). However, if the input level fluctuation is sudden over a period shorter than 100 ms, the fluctuation cannot be absorbed by the conventional method, and the fluctuation is passed on to a next stage as it is.
In the most fundamental WDM configuration, i.e., in the point-to-point configuration, all wavelengths (channels) are input from stable optical sources, such as a transponder, and the probability of the above sudden fluctuation occurring is low. On the other hand, in the case of the add/drop apparatus and the cross connect apparatus, an input wavelength is a signal that is individually branched from an upstream WDM apparatus. For this reason, a sudden, and often big fluctuation (power level change) may occur in the multiplexed optical signal. Unless a countermeasure is provided, the sudden and big level change falls out to a downstream WDM stage, which is the above first problem.
In the case of the add/drop apparatus and the cross connect apparatus, after the multiplexed optical signal is demultiplexed, some or all of the wavelengths are dropped or switched, and the switched wavelengths are multiplexed again, and transmitted. When multiplexing, it is necessary to make the transmitting level of all wavelengths uniform like the point-to-point configuration, requiring the feedback control function using the variable optical attenuator and the optical spectrum analyzer.
Major differences of the add/drop apparatus and the cross connect apparatus compared to the point-to-point configuration are sudden and great variations of the optical input level, which are often caused by change of the upstream output level due to incrementing and decrementing of the wavelengths of an upstream WDM apparatus (since the input to the multiplexing unit is the output of the upstream WDM apparatus), fall of the level due to failure of the optical amplifier, an instantaneous disconnection of the optical signal when changing a path at the optical switch, and an automatic back-off to a safe optical power level when an optical fiber is accidentally disconnected.
By the conventional control method, wherein the feedback speed is low, the sudden level change cannot be absorbed, but is passed on to a downstream WDM apparatus. Accordingly, where the WDM system is configured with multiple stages of add/drop apparatuses and cross connect apparatuses, the level changes are rapidly accumulated and passed downstream, causing receiver damage and signal error. This restricts the number of the stages of add/drop apparatuses and cross connect apparatuses.
Further, an automatic level control (ALC) is often provided for regulating the output power, which poses a risk of the ALC amplifying the sudden and great level change. This restricts the number of repeaters, and, therefore, the transmission distance. As the result, the performance of the transmission system is degraded.
The second problem is related to detection of an input signal that contains an ASE (amplified spontaneous emission). While an ASE is not contained in an optical signal from a stable optical source, as is the case of a point-to-point system, an ASE is contained in an optical signal in the case of the add/drop apparatus and the cross connect apparatus. This is because an ASE is generated when the optical signal passes through the optical amplifier in the upstream WDM apparatus. For this reason, in the case of the add/drop apparatus and the cross connect apparatus, the optical signal input to the VAT (variable optical attenuator) contains an ASE.
A threshold detection level alarm is set up at the VAT for detecting a disconnection and a level decline of the optical signal such that management and triggering of incrementing/decrementing of a wavelength are carried out. At this juncture, if an ASE is contained in the optical signal, detection may become inaccurate, for example, disconnection and level decline in the upstream WDM apparatus are not detected by the downstream VAT.
Consequently, incorrect operations take place, such as a proper optical signal being disconnected, and an optical signal containing only an ASE being transmitted to later stages.
The third problem is related to the dynamic range of the optical signal input to the variable optical attenuator VAT. An optical signal supplied from a stable optical source is relatively well regulated, varying within a range of about ±2 dB under normal operating conditions of, e.g., 0 dBm. On the other hand, in the case of the add/drop apparatus and the cross connect apparatus, an input signal is provided by the upstream WDM apparatus, where various factors cause great variation, which can range ±10 dB. The factors include a loss variation due to a tilting status (explained below) of the upstream WDM apparatus, a loss variation due to path differences relative to branching and adding, and a loss variation due to an increased number of optical connectors.
Although a variable optical attenuator providing a dynamic range of about 30 dB is available, its guaranteed input-and-output linearity range is limited to, e.g., about 10 dB or less. Accordingly, a highly precise level stabilization control with accuracy in the order of 0.1 dB, which is required by WDM, is difficult to obtain by the conventional method.

Wavelength multiplexing method and an apparatus thereof

Abstract: The high speed control is realized by providing a fast-operating local feedback loop for each variable optical attenuator in addition to a slower main feedback loop.


Gene regulation network is reconstructed using time series microarray data under the method of the Bayesian network. Particular power-law function is used to calculate the joint probabilities among genes across time points. This invention discloses the use of the downhill simplex algorithm to find global maxima of interrelational likelihood. Arcs with higher frequencies are selected to establish the gene regulation network. Prior knowledge may be included into candidate gene networks to accelerate search for best networks.

With the advent of DNA microarray technology, researchers can now measure the expression levels of all genes of an organism in a single assay. Measurements have since been carried out to observe the state of cells undergoing developmental program or subjected to experimental/environmental stimuli. Analysis of microarray data by clustering methods has become popular. In the analysis, patterns of gene expressions across time points or different treatments are grouped into clusters. The function of an unknown gene can then be inferred from that of the known genes in the same cluster.
Although cells of the same species carry the same genetic blueprint in the DNA, not all genes express particular features at any given time and what are expressed are always at different levels. Gene products, mainly proteins, run or catalyze the biochemical reactions in living organisms. When and to what extent a gene is regulated by other genes are keys to understand the life. A step beyond clustering is therefore to reconstruct gene regulation networks. Several methods for gene network modeling and reconstruction were thus published.
Simon et al. demonstrated, using the genome-wide transcription factor binding site analysis, the serial regulation of transcription factors during a yeast cell cycle. See Simon et al., "Serial regulation of transcription regulators in the yeast cell cycle," Cell, 106 (2001) 697-708. By serial regulation, it was meant that the transcription activators that function during one stage of the cell cycle regulate the transcription activators/cyclin genes that function during the next stage. In FIG. 4B of their paper is shown such a serial regulatory network. Qian et al. disclosed a technology to use an SVM machine learning approach to reconstructing the cell-cycle gene network. See: Qian et al., "Prediction of regulatory networks: genome-wide identification of transcription factor targets from gene expression data," Bioinformatics, Vol. 19 no. 15 2003, pages 1917-1926. Jansen et al. disclosed a technology to reconstruct a cell-cycle gene network using a database. See: Jasen et al., "A Bayesian Networks Approach for Predicting Protein-Protein Interactions from Genomic Data," Science, Vol. 302, 17 Oct. 2003, p. 449-453. These inventions rely heavily on databases although they also resorted to Bayesian networks. Both require extensive learning before application. In general, in the computational science, good learning depends on informative databases in which answers are buried. New features that are not included in the database cannot be discovered in the machine learning technology. In the case of gene or protein networks, databases with large number of data do not exist and quality of the regulatory relations in the databases is poor. These facts made it difficult to use the machine learning approach in the reconstruction of gene networks. Furthermore, in analyzing the data, a plurality of ad hoc parameters such as thresholds, likelihood cuts etc. are necessary. Interpretation of the data depends deeply on the values of the parameters as selected.
It is thus necessary to provide an innovative method for reconstruction of gene networks from existing noisy data.
It is also necessary to provide a method for reconstruction of gene networks, the levels of detail of the reconstructed gene networks being inversely proportional to the noisiness of the data.
It is also necessary to provide a method for reconstruction of gene networks using a computation-oriented approach.
It is also necessary to provide a method for the reconstruction of gene networks with low false positive rate.
It is also necessary to provide a method for reconstruction of gene networks wherein no ad hoc parameters are necessary.
It is also necessary to provide a method for reconstruction of gene networks from time-series microarray data.
It is also necessary to provide a device for reconstruction of gene networks using all the above methods.

Reconstruction of gene networks and calculating joint probability density using time-series microarray, and a downhill simplex method


An optical unit coupling mechanism for coupling optical units 10, 11 having a plurality of mutually parallel optical paths 10a, 10b with each other, said optical unit coupling mechanism comprising a round dovetail consisting of a male dovetail 1 and a female dovetail 4, wherein said male dovetail 1 has a minor diameter part 1b of predetermined diameter d.sub.2, part 1d of which is sized larger than the diameter d.sub.2 of the minor diameter part 1b. By virtue of this optical unit coupling mechanism, the system performance can be enhanced without causing a system enlargement and the system compatibility can be maintained.

1. Field of The Invention
The present invention relates to an optical unit coupling mechanism for coupling optical units having a plurality of mutually parallel optical paths with each other, in which use is made of a round dovetail.
2. Discussion of Related Art
The above type of optical unit coupling mechanism is commonly employed as means for coupling, for example, individual units of a stereomicroscope as shown in FIG. 11 with each other. In this stereomicroscope, the optical system is now constructed by interposing various units known as intermediate tubes (or intermediate lens barrels), for example, a photographic tube (or photographic lens barrel) 103 and a coaxial falling light illuminator 104 between a zoom lens body 101 and a binocular observation tube (or binocular lens barrel) 102 in order to comply with the user needs diversified year after year. The mechanism for coupling an intermediate tube with the zoom lens body 101, mechanism for coupling the intermediate tubes with each other and mechanism for coupling an intermediate tube with the binocular observation tube 102 generally each comprise the round dovetail disclosed as prior art in Japanese Utility Model Laid-Open No. 11084/1985. Further, Japanese Utility Model Laid-Open No. 164401/1989 discloses a stereomicroscope in which use is made of a combination of prisms and includes a drawing showing the formation of the round dovetail at a lower part of a binocular observation tube through which a pair of light beams pass.
However, the above common optical unit coupling mechanism for achieving coupling of the individual optical units with the use of the round dovetail according to the prior art has involved the following problem. In stereomicroscopes, as mentioned above, the optical system is often constructed by piling two or three intermediate tubes in order to comply with the diversified user needs. In this optical system, the effective diameter of each tube must be satisfactorily large for observing the entire visual field without the occurrence of eclipse, shading or other problem. Further, the effective diameter of the light beam must be large for increasing NA and enlarging the visual field in order to enable performance enhancement.
In the round dovetail disclosed in Japanese Utility Model Laid-Open No. 164401/1989, as shown in FIGS. 12 and 13, the structure thereof is such that fastening is effected by pressing a slant face 111 of the round dovetail. Thus, the diameter d.sub.11 of a minor diameter part 112 forming an abutting joint face is conspicuously small relative to the diameter d.sub.12 of a major diameter part 113 of the round dovetail with the result that the effective diameter d.sub.13 of the light beam is limited by the above diameter d.sub.11 of the minor diameter part 112 forming an abutting joint face. If it is intended to render the effective diameter d.sub.13 of the light beam larger than the diameter d.sub.11 of the minor diameter part 112, either the dovetail per se must be enlarged or the spacing between the right optical axis and the left optical axis must be reduced. However, enlarging the dovetail per se leads to an apparatus enlargement. Further, the spacing between the right optical axis and the left optical axis is nearly entirely determined by the internal angle of the right and left optical axes on an object side, the NA and the size of the apparatus per se, which generally ranges from 22 to 24 mm in Galilean stereomicroscopes, and changing the above spacing is difficult. Still further, the size of the dovetail and the spacing between the optical axes often cannot be changed at all for ensuring a system compatibility.