Operating point trimming methods for an optical waveguide modulator and an optical waveguide switch are disclosed. One operating point trimming method for an optical waveguide modulator comprises, for example, the step of removing, while monitoring the waveform of an intensity modulated light beam, a portion of either one of a first and a second electrode such that the intensity modulated waveform takes on a desired waveform. One operating point trimming method for an optical waveguide switch comprises the step of removing a portion of either one of a first and a second electrode while monitoring output light beams.

The present invention relates to operating point trimming methods for an optical waveguide modulator and an optical waveguide switch.
In a general optical communication system, a light signal intensity modulated on the transmitter side is transmitted to the receiver side through an optical transmission line formed of an optical fiber or the like, and the signal is directly detected and the transmitted information is reproduced on the receiver side. The intensity modulation may be performed on the transmitter side by having the drive current of a light source, which is formed for example of a semiconductor laser, modulated with a modulating signal (direct modulation). In the case of the direct modulation, however, there sometimes occurs a relatively large wavelength shift (chirping) when high speed modulation is performed. Therefore, when an optical fiber whose dispersion characteristic is not good is used as the optical transmission line, the transmission is restricted in the transmission distance or the transmission speed. More specifically, when a system is structured with a combination of a single mode optical fiber exhibiting zero dispersion at 1.3 .mu.m band and a semiconductor laser oscillating at 1.55 .mu.m band minimizing the transmission loss, the system has restriction of the transmission distance or the transmission speed due to the wavelength dispersion. As a means for removing such restriction on the transmission distance or transmission speed, there is an external modulation system using an optical modulator. The external modulation system is a system in which a light beam emitted from a light source at the level of constant intensity is modulated by, for example, an optical waveguide modulator provided independently of the light source and, with which, a system producing an extremely small quantity of wavelength chirping can be formed. In implementing such external modulation system, it is desired that a trimming method for controlling the operating point of the optical waveguide modulator is provided.
FIG. 1 is a plan view showing a structure of a conventional optical waveguide modulator 1.
Referring to FIG. 1, reference numeral 2 denotes a waveguide substrate in a parallelepiped form made from a ferroelectric material such as lithium niobate (LiNbO.sub.3). At a predetermined position on the surface of the waveguide substrate 2, there is formed, by such a method as thermal diffusion of titanium (Ti), an optical waveguide 3 having a first branch optical waveguide 3a and a second branch optical waveguide 3b of the same length and in the form of a combined two Y-branch waveguides. On the surface of the waveguide substrate 2, there is further formed a buffer layer 4 of a silicon dioxide (SiO.sub.2) film for covering all of the optical waveguides 3, 3a, and 3b.
Over the first branch optical waveguide 3a, there is formed, through the buffer layer 4, a first electrode 5a for applying the driving voltage, provided by plating of a conductive material such as gold, and over the second branch optical waveguide 3b, there is formed, through the buffer layer 4, a second electrode 5b. One end of both the first and second electrodes 5a and 5b are connected with a drive circuit (not shown) for changing the voltages applied to the electrodes 5a and 5b according to the modulating signal and the other ends thereof are connected with terminating resistors (not shown). One end portion of the optical waveguide 3 is optically coupled on the waveguide substrate 2 with an optical fiber 6 on the input side as indicated by the arrow and the other end portion thereof is optically coupled with an optical fiber 7 on the output side. The buffer layer 4 is provided so that the light beams propagating through the first and second branch optical waveguides 3a and 3b may not be absorbed by the first and second electrodes 5a and 5b.
With the described arrangement, the refractive indexes of the first and second branch optical waveguides 3a and 3b of the optical waveguide 3 are changed according to the electric fields applied thereto and, hence, the respective branch beams branched by the branch optical waveguides 3a and 3b in phase will suffer phase changes according to the refractive indexes of the respective branch optical waveguides 3a and 3b.
Since, except for the Y-branch portions, the optical waveguide 3 is arranged to be a single mode optical waveguide which propagates only the light beam of the fundamental mode, the intensity of the interference light output from the optical waveguide 3 becomes a maximum when the phase difference between the branch light beams is zero, whereas the intensity of the interference light becomes a minimum when the phase difference between the branch light beams is .pi.. Further, when the phase difference is between 0 and .pi., the interference light takes on an intensity corresponding to the phase difference. In the described manner, the optical waveguide modulator 1 provides time-series changes to the output light intensity by changing the voltages applied to the electrodes according to the modulating signal.
FIG. 2 shows the relationship between the applied voltage and the output light intensity. In the diagram, the output light intensity is indicated along the axis of ordinate and the applied voltage is indicated along the axis of abscissa.
The relationship between the applied voltage V to the Y-branch interferometric optical modulator and the output light intensity P.sub.o, under the conditions that either a TE mode wave or a TM mode wave is used, that the propagating light is equally divided and combined at the Y-branches suffering no loss, and that the wave guide has no loss, is expressed as EQU P.sub.o =Pi.multidot.cos.sup.2 [(.pi./2).multidot.(V/V.pi.)+.theta.],
where Pi represents the input light intensity and V.pi., called the half-wave length voltage, represents the minimum voltage difference providing the maximum output and the minimum output.
The angle .theta. becomes 0 when the optical path difference between the two waveguide paths 3a and 3b equals 0 or .lambda. (wavelength of the propagating light)/n (the refractive index of the medium for the propagating light) multiplied by 2 k (k=.+-.1, .+-.2, . . . ). The solid line 10 in FIG. 2 shows the case where the angle .theta.=0.
In such modulator, the intensity modulation can be achieved by changing the voltage between the applied voltage V.sub.1 (V.sub.3) providing a maximum of the light intensity and the applied voltage V.sub.2 (V.sub.4) providing a minimum of the light intensity. For example, when performing digital modulation, the applied voltage may be set to V.sub.1 at the mark period 10a corresponding to "1" and the applied voltage may be set to V.sub.2 at the space period 10b corresponding to "0".
In the described optical waveguide modulator 1, the refractive indexes of the first and second branch optical waveguides 3a and 3b are changed by stress exerted thereon from the buffer layer 4 and the electrodes 5a and 5b disposed on the waveguide substrate 2 and, as a result, the optical path lengths of these waveguides become different, leading to a shift of the operating point.
When the operating point is shifted as described above, the desired waveform 10 is shifted to the position of the waveform 11 as indicted in FIG. 2 by the broken line. More specifically, the waveform is shifted by the shift amount .delta.V corresponding to the operating point shifting. In order to compensate for this shift, it is required that a DC bias voltage is applied to the electrodes 5a and 5b to change the refractive indexes of the branch optical waveguides 3a and 3b and adjust the optical path difference therebetween.
The shift amount .delta.V due to the operating point shifting differs from product to product because of lack of uniformity of the thickness of the evaporation film of the buffer layer etc. and of the size of various parts occurring in the course of fabrication. Such tendency is especially remarkable with optical waveguide modulators using, as the waveguide substrate, LiNbO.sub.3 having the photoelastic effect. Therefore, it becomes necessary to apply each optical modulator with the DC bias voltage corresponding to the operating point shift amount .delta.V due to the operating point shifting resulted from the above described lack of uniformity to thereby adjust the DC offset. Further, even if the shift amount .delta.V is compensated for by taking the above measure, there sometimes occurs, when such DC bias voltage is applied, a phenomenon called DC drift in which the operating point shifts with the lapse of time after the application of the DC bias voltage. This phenomenon for example is such, as shown in FIG. 3, that the waveform 10 adjusted to a desired output light intensity by application of a DC bias tends to shift to the waveform 12 indicated by the broken line.
When such a shift occurs, the applied voltage V.sub.1 providing the maximum light output is shifted to V.sub.1 ', as shown in FIG. 3, while the applied voltage V.sub.2 providing the minimum light output is shifted to V.sub.2 '. Therefore, if the modulation is performed with the applied voltages V.sub.1 -V.sub.2 whereby the original waveform 10 was obtained, the output light intensity when the applied voltage is V.sub.1 decreases from 10a to 10b as shown in the same diagram, while the output light intensity 12a when the applied voltage is V.sub.2 increases from 12a to 12b. As a result, it becomes impossible to obtain the maximum and minimum output light beams and the extinction ration (the ratio of the output light intensity in the mark period to that in the space period given in decibels) is decreased, and a problem is presented that it becomes unable to have a suitable optical signal output.
When it is attempted to obtain optical waveguide modulators having no operating point shifting such as the DC drift, since some nonuniformity of the operating point occurs in the fabrication process, it becomes necessary to select such products that have virtually equal operating point shiftings after fabrication thereof. This is indeed a difficult task in view of the fact that the nonuniformity of the operating point shifting is frequently produced in the fabrication process, and because of which, a problem is presented of a lowering of the yield rate.

Operating point trimming method for optical waveguide modulator and switch


An electroplating apparatus (11) has a conveying system (19), which passes the printed circuit boards on a horizontal passage path through the treatment chamber (13). They are contacted by tong-like grippers (32), which run upstream of the leading edge (63) of the circuit board and in this area engage thereon from above and below. The gripers (32) are fixed to transverse beams (29), which are guided on both sides by chains (26) and electrically contacted by contact rails (39). Thus, the circuit boards (12) are moved in a horizontal, central path and simultaneously contacted. Alternatively the circuit boards (12) can be conveyed between electrically connected contact roll pairs (21), which are conveyed by an upper and lower conveyor (20a, b) and automatically rotate in order to convey the circuit boards at high speed.

U.S. Pat. No. 4,755,271 and U.S. Pat. No. 4,776,939 disclose electroplating apparatures, in which printed circuit boards are passed horizontally through a treatment chamber. At the edge of the treatment chamber and optionally separated by a shield, are provided conveyors, such as chain conveyors, which grip the circuit boards in tong-like manner from the side and in this way guide them through the treatment chamber. In the latter copper is electrolytically applied, the power supply being provided via the tongs. When using tong guides on both sides only one circuit board width can be treated.
DE-32 36 545 C2 discloses an apparatus, in which the lateral guidance of the circuit boards is provided by contact rolls positioned behind a shield. A sliding guide can be provided on the other circuit board side.
These arrangements only operate in a satisfactory manner with circuit boards of a uniform size. When using circuit boards which are narrower than the passage path, as a result of their one-sided guidance and contacting they pass asymmetrically through the treatment chamber. As the treatment liquid, i.e. the electrolyte is vigorously moved, they are then unreliably guided or the guides on the free side must be separately adjusted for each circuit board width. Therefore it is not possible to treat several circuit board sizes in alternating manner in the apparatus. In the case of electrolytic treatment the asymmetry also requires a partial covering of the anodes, because otherwise the electroplating application is non-uniform over the width.

Apparatus for the galvanic treatment of articles


A method of erasing information on one or more disks in a disk drive uses a high strength magnetic field to erase the disks while the disks are in the HDD assembly. The design of the head disk enclosure provides a reduced thickness in a localized region over the disks. This allows a narrower working magnetic gap of the HDD level disk erase apparatus. The localized region of the HDD may be a formed indentation on the top cover, elimination of flange, and reduced floor thickness of the HDD base.

1. Technical Field
The present invention relates in general to an improved hard disk drive design and, in particular, to an improved method of erasing or preconditioning the magnetic media of the disk or disks in a hard disk drive at the assembly level.
2. Description of the Related Art
Generally, a data access and storage system consists of one or more storage devices that store data on magnetic storage media. For example, a magnetic storage device is known as a direct access storage device (DASD) or a hard disk drive (HDD) and includes one or more disks, read/write head(s) with actuator and associated controller and electronics to manage local operations concerning the actuator, disks and data stored on the disks. The hard disk(s) themselves are usually made of a substrate of aluminum alloy or a mixture of glass and ceramic, and are covered with a magnetic film coating. The magnetic coating can be several layers of different metal alloys. Typically, the one or more disks are coaxially positioned on a common spindle that is turned by a disk drive motor at several thousand revolutions per minute (rpm).
The disk(s), motorized spindle, read/write heads and actuator are all enclosed using a base and top cover. This assembly level is typically called a head disk enclosure (HDE). The HDE is sealed to maintain an exceptionally clean environment for the read/write heads and recording media. The read/write head, connected to a suspension and arm assembly, is linearly or pivotally moved utilizing a magnet/coil structure that is often called a voice coil motor (VCM). The stator of a VCM is mounted to a base plate or casting on which the spindle is also mounted. The base casting with its spindle, actuator VCM, and internal filtration system is then enclosed with a cover and seal assembly to ensure that no contaminants can enter and adversely affect the reliability of the read/write head or disk media.
A motor, typically a brushless DC motor, is used to rotate the disk. The disk is mounted and clamped to a hub of the motor. The hub provides a disk mounting surface and a means to attach an additional part or parts to clamp the disk to the hub. In most typical motor configurations of HDDs (hard disk drives), the rotating part of the motor (the rotor) is attached to or is an integral part of the hub. The rotor consists of a ring-shaped magnet with alternating magnetic north/south poles arranged radially and a ferrous metal backing. The magnet interacts with the motor's stator by means of magnetic forces. Magnetic fields and resulting magnetic forces are induced via the electric current in the coiled wire of the motor stator. The ferrous metal backing of the rotor acts as a magnetic return path. For smooth and proper operation of the motor, the rotor magnet magnetic pole pattern should not be substantially altered after it is magnetically charged during the motor's manufacturing process.
The disk recording media typically has several layers that make up a compound magnetic structure. The structure typically includes a high moment soft underlayer and a magnetic top layers which may magnetically couple and help achieve improved magnetic stability, low noise and increased coercivity. The disk magnetic media may be a plurality of compositions and layered designs and could be either longitudinal or perpendicular in orientation of magnetic domains. An external magnetic field can be applied to the disk for preconditioning by orienting the media or erasing any servo pattern data. The required direction of the magnetic field is dependent on the magnetic film media design.
A process called "disk erase" is often a necessary part of manufacturing an HDD. Disk erase involves preconditioning the media by orienting the magnetic domains of the disk's magnetic layer in a consistent uniform state. This process can initially be done prior to HDD assembly as part of the disk manufacturing process, or ideally, while the disk is in the HDE. In addition to initial HDD assembly, disk erase is needed for HDDs that have failed the HDD test or servo write process and have to be reworked by repeating the servo write process. In such cases it would be prohibitively expensive to remove the disk and perform a disk level erase. It is most cost effective to "erase" the disk(s) while they are in the HDE. This can be achieved by one of several methods: 1. use the HDD product read/write heads to write a fixed and uniform pattern over the disk thereby erasing any prior servo pattern. 2. Use a special write head or magnet which enters into the HDE through a port or window in the top cover or base casting. Such port or window would be sealed during normal HDD operation. 3. Expose a portion of the HDE which houses the disk to a high intensity magnetic field while spinning the disk(s).
The method that uses the product heard to erase the disk track by track takes significant time because the head must erase each individual track, one at a time, and progressively move from track to track. Also, the process using the product head is typically done at the servo track write (STW) process, which is currently the single most expensive HDD manufacturing assembly and/or test process due primarily to the cost of the equipment and its relatively limited production capacity throughput.
A method that uses a special manufacturing process write head or a bar magnet brought close to the surface of the disk to erase the disk can have some advantages over using the product head. Such a process can be faster but a disadvantage of this process is that it requires a hole or access port in HDE to allow entry of the special process head or magnet. In addition, this process would have to be performed in a clean environment to prevent contaminants from entering the HDE through the magnet access port.
The third method, exposing a portion of the HDE that houses the disk to a high intensity magnetic field via an HDE level disk erase apparatus, is most desirable for several reasons: 1) it does not require opening up the HDE which would require time and expense and exposes the HDE to possible contamination, and 2) it is fastest and can be performed on fairly simple inexpensive equipment. This method does require that the materials of the top cover and base be non-magnetic. Such use of non-magnetic materials for top cover and base is current state of the art, usual practice.
Although HDE level disk erase is most advantageous, there are several limiting problems:    1. Increasing disk coercivity makes it increasingly difficult to erase the disk    2. The innermost area of the disk is difficult to erase without magnetically damaging the motor rotor    3. Eddy current effects when using aluminum disk substrates make it difficult to control spinning the disks.
With successive HDD products of increased areal density the disk media coercivity is increasing. The increased, coercivity of the disk increases the resistance to demagnetization (i.e., changing the state of the magnetic domains), thus requiring an increased demagnetizing force to erase the disk (write to the disk). Increasing the magnetic field strength of an HDD level disk erase machine exacerbates the problem of modifying, i.e., damaging, (via demagnetization) the spindle motor rotor. Thus, a method is needed to: (1) increase the magnetic field strength of an HDD level disk eraser, and (2) increase the magnetic field without increasing the magnetic field near the spindle motor rotor and/or a method of protecting the spindle motor rotor magnet.
With perpendicular recording media the required magnetic field direction of an HDE level disk erase apparatus is different than that typically used for longitudinal recording media. The required direction is dependent on the design of the compound layers of the media and can be perpendicular to the disk. For longitudinal recording the usual required direction is tangential with respect to the disk.
With increasing magnetic data areal density there is a trend towards an increase in the proportion of HDDs having only one disk. For HDDs having only one disk, it is possible to have an enclosure design, which provides a minimum distance between the disk surface and the outer surface of the enclosure. Such a design could allow for the magnets of a disk erase apparatus to be much closer to the disk and allow for an improved disk erase machine.

This patent is subject to a terminal disclaimer.


The present invention includes compositions and methods for the use of an encapsulation additive having between about 0.1 to about 30 percent isolated and purified vitelline protein B to provide for mixed and extended release formulations.

Without limiting the scope of the invention, its background is described in connection with polymeric encapsulation of compounds.
The encapsulation of pharmaceuticals and other compounds is of continuing interest, both in industry and in academia. Encapsulation may be used to modify the time-release properties of a material, to alter the solubility of a material and/or to provide other desirable property modifications. Polymers, biopolymers and peptides have been explored for their suitability as microencapsulation agents.
Microcapsules include, generally, a core material (liquid or solid) encased in a specialized coating. Microencapsulation technology has found widespread use in the pharmaceutical area, for example, coating of drugs to extend or delay their release or target their release to a specific area of the digestive tract. Other interesting applications include encapsulation of ink in carbonless carbon paper, encapsulation of perfumes in 'scratch and sniff' types of promotionals and encapsulation of living pancreatic cells to treat diabetes. In the case of living cells, the pore size of the microcapsule is selected to prevent the passage of host antibodies while allowing the free exchange of insulin and glucagon. Microcapsules have also found application in the food, cleaning, adhesives, fertilizers and aerospace industries to name a few.
Albumin has been used in the preparation of microcapsules. Two technologies have been used—coacervation, or oil in water emulsions. These techniques have been the source of many publications, including Zimmer et al. (J. Controlled Release 33: 31-46 (1995)); Cremers et al. (Biomaterials 15(1): 38-48 (1994)); Deasy (Microencapsulation and Related Drug Processes; Marcel Dekker, Inc., NY (1984)); and Tomlinson, E. and Burger, J. J. Methods Enzymol. 112: 27-43 (1985)). Despite the efforts made towards developing microencapsulation methods, there still exists a need for novel and effective materials for the encapsulation of various materials.

Use of vitelline protein B as a microencapsulating additive

THE REGENTS OF THE UNIVERSITY OF CALIFORNIA


Freezer for biosanitary and cytotoxic waste, which comprises an inner space that houses a waste container, a front door through which the waste container in the inner space is inserted/removed, an upper door through which waste is poured into the inner container, cooling means and inner space temperature control means, wherein, the freezer further comprises an air purifier that treats an air stream coming from the inner space, when opening one of its doors, thus avoiding the emission of both chemical and biological particulate contaminants to the outside environment.

Different designs of refrigerators for biosanitary and cytotoxic waste are known. For example, the one shown in Spanish utility model ES 1062531 U, published on 1 Jul. 2006, which comprises a front door that allows insertion and removal of a container where the waste is deposited, an upper door to pour the waste into the container. The refrigerator has respective coils arranged on the side walls and rear wall, as well as a thermostat that regulates the temperature inside the refrigerator.
These known refrigerators have the disadvantage that, when opening either the upper door or the front door, both chemical and biological particulate contaminants are emitted to the outside environment together with the air stream coming from the interior of the refrigerator.
For this reason, a freezer for biosanitary and cytotoxic waste needs to be designed, which is able to simply and economically solve the disadvantage of the aforementioned prior art.


Apparatus and method capable of preparing samples adapted for observations by electron microscopy. Each sample is ion-etched. During this process, the sample stage is tilted reciprocably left and right about a tilting axis. The sample is ion-etched together with a shielding material. The sample may contain a substance that is not easily etched by the ion beam. In the present invention, such unetched portions are not produced in spite of the presence of the substance. The substance can be separated from the sample. The ion beam is directed at the sample with the boundary defined by an end surface of the shielding material. Portions of the sample at a processing position and its vicinities are etched by the beam.

1. Field of the Invention
The present invention relates to an apparatus and method for preparing samples observed on a scanning electron microscope, transmission electron microscope, or other instrument.
2. Description of Related Art
One known apparatus for preparing samples to be observed on a scanning electron microscope (SEM) or transmission electron microscope (TEM) is described, for example, in Japanese Patent No. 3263920. This known apparatus is an ion beam processing system that processes a sample into a shape adapted for SEM or TEM observation by irradiating the sample with an ion beam to etch it.
Furthermore, in the ion beam processing system of Japanese Patent No. 3263920, a shielding material is placed over the sample, and the sample is processed by the ion beam directed at the sample with the boundary defined by an end surface of the shielding material. As a result of this ion beam processing, an electron microscopy sample having a desired cross section is completed.
The sample prepared by the ion beam processing system described above is set on a SEM or TEM. The cross section of the sample produced by the ion etching is irradiated with an electron beam and observed.
If the sample contains a substance M that is not easily etched by the ion beam, as shown in FIG. 1(a), the portion hidden by the substance M is not etched by the ion beam processing system of Japanese Patent No. 3263920, but left behind. As a result, after the etching, the sample assumes a shape, for example, as shown in FIG. 1(b). The unetched portion Sa creates an obstacle in observing the desired cross section Sb by electron microscopy, though the cross section has been produced as a result of considerable effort.

Apparatus and method for preparing samples


This invention relates to a method of treating a livestock footbath solution comprising adding an alkali metal bisulfate to the solution. The invention also relates to a method of treating a livestock footbath solution comprising adding to the solution a blend of an alkali metal bisulfate and a material to treat a bacterial disease. The invention also relates to a method of treating a livestock footbath solution comprising rotating the addition to the solution of an alkali metal bisulfate and a material to treat a bacterial disease.

This invention relates in general to livestock footbaths, and in particular to a method of treating livestock footbath solutions to improve the solutions.
Bacterial diseases of the hoof, such as hairy hoof warts and hoof rot, are common in livestock such as cattle, sheep, goats and horses. These diseases can cause lameness which leads to a decline in animal health and performance as measured by a decrease in body weight and fertility. Animals that are seriously afflicted may need to be culled. Lameness in dairy cattle often causes a significant decrease in milk production. Thus, the bacterial diseases create a financial burden on farmers as well as harming the livestock.
One method to address the disease problem is by the use of a livestock footbath. The footbath holds a solution containing a material to prevent and/or treat the disease, such as an antibiotic or other material such as copper sulfate and/or zinc sulfate. The animal is led to walk through the footbath to immerse the hooves in the treatment solution. For example, dairy cattle are usually led through a footbath on their way to or from the milking parlor.
There are still problems associated with the use of livestock footbaths. Some materials used in footbath solutions are not very effective against the diseases or cause irritation to the hooves of the animals. Another problem is that bacteria-containing organic materials on the hooves of the animals are washed off in the footbath solution. The organic materials build up over time and overcome the ability of the material in the solution to prevent and/or treat the disease. An additional problem is that disposal of the footbath water may raise environmental concerns, as several states are mandating the discontinued use of products containing heavy metals such as copper. Therefore, it would be desirable to provide improved livestock footbath solutions.

Method of treating livestock footbath solutions


A lightweight holding device for releasably attaching a chemiluminescent light stick to a fishing float is disclosed. The device includes a first side for releasably attaching to the fishing float, and a second side for releasably holding a chemiluminescent light stick. The first side typically includes two pairs of gripping arms, one at the top and one at the bottom, which are able to releasably receive a portion of the fishing float. The second side typically includes two pedestals, one at the top and one at the bottom, each of which are able to releasably receive an end of the light stick. The top pedestal typically defines a ceiling pocket, and the bottom pedestal a floor pocket, for one of the ends of the light stick to fit into. The first and second sides are typically integrally formed and oriented to face away from one another.

Fishing floats or bobbers are commonly used in fishing to control the depth at which a baited hook or lure is suspended and to indicate when a fish has taken the hook. When a fish takes the bait or lure, the attached bobber will move, alerting the fisherman to the presence of a fish on the line. Various conditions and types of fishing call for various sizes and types of bobbers. Specific types of floats or bobbers include foam, crappie, panfish and torpedo. Some floats are particularly adapted for night fishing by being equipped with lighting apparatus for improved visibility at night.
The advantages of night fishing have long been recognized since many species of fish feed well into the night or early in the morning before the sun rises. One example of a night feeding fish is the shovelhead catfish, a.k.a. flathead, yellow cat, and mudcat catfish. These catfish have a homesite where they rest during the day and from which they journey on their nocturnal feeding forays. A submerged stump, a hollow log, a bank den of muskrat or beaver, a pile of boulders or an undercut ledge is an excellent resting site for a shovelhead.
Trotline fishing is a means of assembling many lines at once for fishing, and keeping track of the lines can become a problem, especially at night. The absence of light during night fishing introduces problems which are not experienced during daylight fishing. For a trotline fisherman with many lines in the water, a float serves to indicate where a particular line is located. In addition to the difficulty of locating a float at night, often considerable difficulty is experienced seeing the movement of the float, so that is it difficult to determine if a fish is taking the bait or not. Consequently, previous inventions typically include some type of battery-powered light or fluorescent material attached to the bobber to provide a visual indication of its position during night fishing.
One of the difficulties with the prior art devices which provide light for floats is that some of the devices require bulky batteries to power a light bulb, while others require a unique and/or expensive style of bobber in which to hold the light. Electrical devices are vulnerable to short circuiting in the water, and many of the working parts will rust and cease to function. Floats which are specifically designed to hold chemiluminescent light capsules for night fishing often can only be used at night, and require the fisherman to purchase two sets of equipment, one for day fishing and one for night fishing.
Thus, there is a need for a device to assist the fisherman who is fishing at night to determine where the bobber or float is located. There is also a need for indicating movement of the bobber in the dark so that the night fisherman can recognize that a fish is biting. It would also be advantageous to provide an illumination device for a float that is not battery powered, is light weight, and has very few if any working parts. It would also be advantageous to provide a simple device that can be attached to an existing fishing float or bobber so that the fisherman can use the same equipment while fishing either during the day or at night. It is also desirable to provide a float or bobber that includes a side compartment for a chemiluminescent light to be easily placed so that the bobber can be used day or night. These and other features and advantages of the present invention will become more apparent with reference to the accompanying specification and claims.

Light stick holding device for a fishing float


A radio broadcasting system for a composite signal consisting of a frequency modulated (fm) analog signal and a multicarrier modulated digital signal is provided which is resistive to multipath degradation. The fm signal and the digital multicarrier modulated signal are fully coherent. The digital signal uses a plurality of carriers having a maximum amplitude at least 20 dB below the unmodulated fm signal. The multicarrier modulated signal is phase locked to a recovered analog fm pilot tone in the composite baseband spectrum of the fm signal which is at least 20 dB above the multicarrier modulated signal, which enables rapid and reliable acquisition of signal for coherent detection. In a specific embodiment the multicarrier modulated signal is a synthesized vector-modulated signal which is a quadrature phase shift keyed (QPSK) modulated set of synthesized carriers each occupying 9.5 kHz of spectrum replicated twenty-one times within a 199.5 kHz bandwidth with no more than two bits per vector. An efficient channel coding consisting of high efficiency block coding, such as BCH 255, 239 code, is employed in connection with time interleaving of bits to mitigate the effects of frequency selective multipath and broadband multipath. The broadcast system is designed to be used in support of compressed digital audio programming material. In demodulation, a demodulator is phased-locked to the recovered high-amplitude analog pilot tone to coherently demodulate the digital signal, to deinterleave, to decode the block encoded signal and to format the recovered data stream for source decoding.

This invention relates generally to the field of digital broadcast communication through the medium of free space, and more particularly, to the field of digital audio broadcasting in spectral regions relying on line-of-sight communications subject to signal fade due to multipath propagation.
In recent years, the quality of commercial audio broadcast signals as delivered by radio transmitters through free space has been eclipsed by the quality of stored program material such as compact digital audio disk technology and digital audio tape technology. The quality differential of stored program material over conventional analog frequency modulated broadcasting is so great that there has been a market shift in listener preference to stored program material. In the past, commercial frequency modulated broadcast signals were considered comparable in quality to stored program material. However, the increase in quality of stored program material and the degradation in fm signal quality, particularly in urban areas, has resulted in a differential in quality that is reflected in decrease in listenership and substantial revenue loss to broadcasters.
One of the reasons for degradation in quality of fm signals is the inherent problems with line of sight propagation of radio signals. Radio signals are subject to interference and fading from specularly-reflected copies of the signal, both narrow-band and broadband. The interference is commonly referred to as multipath. Multipath results in fade which is dependent upon frequency, time and spatial factors. However, a free space signal is generally unaffected by group delay, which is generally associated with other types of media such as copper wires, coaxial cables, fiber optics and waveguides. A careful analysis of the propagation problem in connection with other limiting factors, such as other available spectrum and compatibility with other broadcast services, has revealed that no system exists or is even been suggested as suitable to address the problem of delivering a high-quality broadcast signal of sufficient efficiency and practicality to be commercially viable.
One digital audio broadcasting scheme promoted as potentially viable is designated the Eureka 147 Project. Based on an implementation in the 1500 Hz microwave L-band, the Eureka 147 system proposes a single-transmitter, thirty-three channel system having a 7 MHz bandwidth and relying on an error-correcting convolutional encoding and decoding scheme. Implementation of such a system would involve substantial economic dislocation within the U.S. broadcast market and further, would require that the power be as much as 500 times higher than current analog broadcasting system power to operate comparably at the frequencies of interest. Of technical interest, the Eureka 147 system as proposed would not be able to share spectrum with any other broadcast service, and the use of the system would require that there be a central transmitter in each market and thus that each market be limited to thirty-three channels. The scheme, as proposed, is not particularly spectrum efficient, requiring guard bands between channels to mitigate against intersymbol interference. The system is intended to be multipath resistant. To this end there is a broad spectrum allocation of 7 MHz and a digitally-based error correction scheme.
The problem of reliable transmission and reception in the presence of severe multipath propagation has been explored in the past. For example, Cimini, Jr., reports in a paper entitled "Analysis and Simulation of a Digital Mobile Channel Using Orthogonal Frequency Division Multiplexing," IEEE Transactions on Communications. Vol. COM-33, No. 7, pp. 665-675 (July 1985), that broadband, narrow-band and time-dependent multipath problems in a harsh mobile environment are a substantial challenge to solve. The problems addressed therein presuppose the application of speech/data transmission on a frequency carrier at 850 MHz. Simulations were performed based on orthogonal frequency division multiplexing (a plurality of subcarriers or multitone modulation) with the 7.5 kHz channel bandwidth. Detection was based on coherent detection using one or more pilot signals transmitted in the same manner and at the same amplitude as the information signals. It was assumed that the co-channel interference would be at least 17 dB below the information carrier signals. Cimini identified that reliable retrieval of pilot signals is essential for accurate coherent detection and correction of data. Proposed specifically was a dual pilot system with interpolation in frequency between the pilots and orthogonal frequency division multiplexing wherein each tone is modulated by a quadrature phase shift keyed (QPSK) modulator. It was therein recognized that quadrature phase shift keying had a 3 dB advantage in gain over differential quadrature phase shift keyed modulation and detection.
Error correction techniques are well known for correcting errors in digitally-modulated information signals. The use of error correction techniques provide substantial advantage over conventional analog signaling because detection of less than a complete portion of the signal can still result in recovery of all of the information intended to be communicated. The exact form of error correction and encoding plays a significant role in the efficiency and integrity of the transmitted signal. It is important for example that the selected error correction technique be one which does not so degrade the channel efficiency as to render it impractical.
Multiple-channel digital transmission systems have been known in various environments. For example, the U.S. Military RAKE System is described in "Modern Communication Principles," by S. Stein and J. J. Jones (McGraw Hill, 1967). Other references on multi-channel digital transmission systems include: D. L. Nielson, "Microwave Propagation and Noise Measurements for Mobile Digital Radio Application," SRI Report for ARPA SRI Project 2325, NTIS No. ADB073934C (January 1975); W. W. Peterson, E. J. Weldon, Jr., Error-Correction Codes, MIT Press (1973); and Shu Lin, An Introduction to Error-Correcting Codes, Prentice Hall (1970).
Multiple-channel digital modulation techniques are also known and have been used in telephone line modem technology, such described in U.S. Pat. No. 4,206,320 to Keasler et al. (June 1980), U.S. Pat. No. 4,438,511 to Baran (March 1984), U.S. Pat. No. 4,601,045 to Lubarsky (July 1986) and U.S. Pat. No. 4,754,458 to Dornstetter (June 1988) . The last-named patent is believed to describe a technology in the proposed Eureka 147 system. The Dornstetter patent describes the use of a digital modulation scheme capable of correcting certain types of errors and specifically, burst errors. The system uses convolutional coding and a decoding algorithm based on a Berlekamp-Massey algorithm. The error correction scheme is based on the calculation of coefficients of code words by obtaining polynomials from the factorization over a Galois field of elements. The result is a relatively inefficient use of bandwidth.
An instructive survey article on multicarrier modulation is by John A. C. Bingham, entitled "Multicarrier Modulation for Data Transmission: An Idea Whose Time Has Come," IEEE Communications Magazine, Vol. 28, No. 5, pp. 5-14 (May 1990). This article deals with many of the problems related to multicarrier modulation and identifies areas requiring further development. The principal focus of use of multicarrier modulation has, however, been in connection with communication through impaired channels, such as telephone lines. Frequently, in such environments, there is two-way communication to promote retransmission of lost information.
What is needed is a one-way (broadcast) transmission system which is efficient and sufficiently robust to be able to communicate high-fidelity audio program material in a manner which is compatible with existing U.S. broadcast services, particularly fm broadcast services.

Method and apparatus for digital audio broadcasting and reception


A corrugated paperboard blank that folds together to form a container for enclosing a tank or other fragile article. A pair of seats space the article from a bottom and an upper support extends inwardly to hold the article from movement during shipping and handling. A support panel foldably attaches to an offset flange at an upper edge of the container. The flange spaces the support panel below the upper edge of the container for holding items, such as a lid, separate from the article in the container. The container closes without staples or adhesive for opening, inspection of the articles and reclosing.

Bathroom fixtures such as sinks and commodes are typically manufactured of a ceramic material known as vitreous china. This clay-like material is heavy yet easily molded in a liquidified form for making such fixtures. After molding the material is sprayed with a glaze and baked in a kiln. The glaze cures to a smooth hard finish. The ceramic material, however, is also fragile, and does not readily withstand shocks or sharp hits. Chips, cracks, and other damage to fixtures may occur during storage, shipping, and handling.
Commodes typically found in bathroom facilities have two sections. These sections are a bowl and a tank. After installation, the bowl supports the tank on a back portion. The tank connects to the bowl for communication of water through a flange tube to the bowl. The tank typically is a substantially rectangular cube in appearance, having a length and height greater than the width. The tank has a partially closed bottom that typically defines two openings. One opening provides a fresh water inlet into the tank. A valve mounts in the hole and a pipe extends outwardly through the hole for mating engagement with a supply pipe connected to a supply of water. The bottom further defines the second opening that includes a flange tube extending outwardly from the bottom. The flange tube inserts into the tank and to communicate water to the bowl. The top of the tank typically is open. A removable lid closes the open top after installation. The bowl and the tank typically are packaged and shipped in separate containers.
The fragile nature of the bowl and tank as discussed above impose unique requirements for a container for these goods. The container must enclose the bowl and tank for handling, storing and shipping. The container protects the goods from ships, scrapes, and other damage. Further, the container provides a support structure for handling of the bowl and tank. Often these containers are stacked one on another in order to conserve warehouse space and facilitate handling of the goods. Stacking reduces the labor and the storage costs associated with handling and storing these goods. Many of these products are manufactured in a foreign country and shipped long distances with repeated handling.
Corrugated paperboard containers have been used for storing and shipping such bowls and tanks. Generally, two different types of containers have been used to hold bowls and tanks. The container for the bowl typically folds from a single sheet of corrugated paperboard. The sheet includes scores that define a pair of side walls, a bottom and a top. The edges join together to form a container body. For example, in many of the known containers a flange folds upwardly from the bottom against a lower edge of one of the side walls. Staples connect the flange to the side wall. Each side wall also typically includes a pair of end walls foldably attached to the sides of the side wall. The bottom has an end flap that folds upwardly. The top has an end flap that folds downwardly. The end flaps on the bottom and top fold to partially close the ends of the container. The end walls then fold inwardly perpendicular to the respective side wall to close the ends. Staples or adhesive secure the end walls to the end flaps. The inner surface of one end wall typically overlaps the outer surface of another of the end walls. In another embodiment, the top comprises a pair of panels that each foldably attach to a respective side wall. In this embodiment, the bottom flap and the top flap foldably attach to a first of the end walls on each end. The first end wall folds inwardly with the bottom flap contacting the bottom of the container. The second of the end walls folds inwardly of the first and has a bottom edge that contacts the bottom flap. The first end wall then overlaps the second end wall. Adhesive secures the top flap on the end walls to the top panels to hold the container closed.
One container for holding a tank is known in the industry as a regular slotted container. The container is manufactured from a single blank of corrugated paperboard having scores to define four wall panels. A manufacturer's joint joins the longitudinal ends together in order to form a tubular container. A manufacturer's joint is well known in the industry, and comprises a flap on one side that joins the longitudinal ends together. A plurality of flaps attach along a bottom edge and a top edge of the wall panels. These flaps fold to close a bottom and a top of the container. The flaps and the manufacturer's joint typically are sealed with adhesive, staples, tape, or a combination.
The tank is placed inside the container by the manufacturer. To protect the tank from shocks and handling damage, a liner is first positioned on the bottom formed by the folded flaps. The liner typically is a sheet of foam or of corrugated paperboard. The tank sits on the liner sheet to cushion the tank and thereby avoid damage that can occur from shocks and rough handling. The lid is also placed in the container for shipping with the tank. A spacer inserts between the lid and the tank. The spacer typically comprises a separate foam or corrugated paperboard sheet or a plurality of corner tabs, which cushion contact between the lid and the tank. The container typically includes flaps that are then folded over to close the container. Staples, adhesive and tape are used to secure the flaps to the container.
While meeting the need for a container to hold ceramic tanks for commodes, the corrugated paperboard container discussed above has drawbacks which limit its usefulness. To pack the tanks in these corrugated paperboard containers requires maintaining an inventory of a number of component parts. These parts include the various liner sheets to cushion the tank and the lid. On an assembly line, the parts must be picked and inserted during packing which increases the time to package such goods.
Closing the container requires the use of staples, adhesive, tape, or a combination. The container, however, sometimes does not stay together, despite these mechanisms to hold the container together. In some instances, the container collapses or opens through rough handling. In other cases, the container is opened at a retail center by a consumer seeking to inspect the goods in the container. If the consumer does not purchase the product, it is then more difficult to sell the goods in the opened container. Consumers typically dislike purchasing an opened item. The open container suggests parts are missing or the goods are possibly damaged. An open container may also result in damage to the tank or cause injury to persons. For example, the tank may fall out of the container or other articles may contact the tank during shipping or handling, and thereby cause damage. The tank may fall and hit a person or break on the floor.
Accordingly, there is a need in the art for an improved container for packaging, storing and shipping vitreous china tanks for commodes.


Advanced islet separation technology incorporates an automated method, automated control methodology, process control interface, and automated apparatus to separate (isolate) and process pancreatic islets in a tissue suspension in physiologic process solution, utilizing microprocessor control and/or microprocessor computer control and software programming (code) to interface and control the process temperature, fluid flow rate, pH, dissolved oxygen concentration, endotoxin concentration, dissolved nitric oxide concentration, nitric oxide synthase activity, proteolytic enzyme activity, and/or pressure of the islet containing physiologic process solution, the extent of islet separation, including real-time data acquisition and recording of process variables.

The present invention relates to the isolation of pancreatic islets for transplantation into diabetic patients. In preferred embodiments, the invention presents Advanced Islet Separation Technology, an automated method of islet isolation (separation), an automated process control methodology, process control interface, and an automated apparatus to separate and process pancreatic islets in physiologic process solution utilizing microprocessor control and/or computer control of the process variables and automated apparatus, and the extent of islet separation. The invention may be uniformly applied to islets harvested from animals and mammals, either transgenic or non-transgenic.
The islets of Langerhans, endocrine tissue containing insulin producing beta cells, represent about one to two percent of the total mass of the human pancreas. Separation or isolation of the islets from the connective matrix and remaining exocrine tissue is advantageous and beneficial for laboratory experimentation and transplantation purposes. Islet transplantation is a most promising and minimally physiologically invasive procedure for treatment of type I diabetes mellitus. Transplanting islets rather than complete pancreatic tissue has the distinct advantages of ease of transplantation, and the elimination of the pancreatic exocrine function of the donor tissue involving secretion of digestive enzymes. Liberating islets from pancreatic exocrine tissue is the initial and crucial step that influences islet transplantations. The important objective in islet isolations is to provide sufficient numbers of viable functional and potent islets for transplantation.
Collagenases, metalloendoproteinases that cleave collagen into smaller peptide fragments, are zinc-containing enzymes that require divalent calcium as a cofactor for stabilization and optimal activity. Using traditional collagenases detrimentally affects pancreatic digestion due to the impurities present in the collagenase solutions. Traditional collagenase preparations are concentrated from bacterial (Clostridium histolyticum) culture supernatants. Roche, a manufacturer of molecular biochemicals, states that such collagenase preparations are heterogeneous, containing as many as 30 different enzymes, pigments, cellular debris, and endotoxins. The most significant liabilities of traditional collagenase are variability and endotoxin levels. In traditional collagenase, the primary enzymatic constituent is collagenase, classes I and II. Other proteases found include neutral protease, clostripain, elastase, trypsin, and aminopeptidase.
While larger scale islet separation from human pancreata has become possible with advances in technology, the current techniques cited herein fall short in terms of efficiency, and are inadequate for scale up or mass production in which many donor pancreata are processed at different research and transplantation centers, medical facilities, or commercial locations. In consideration of the lack of donor pancreata, current islet isolation techniques are also inadequate to continuously and repetitively batch process porcine pancreata, or pancreata from animals or mammals, transgenic or non-transgenic, to produce islets for xenotransplantation. In the current techniques cited herein and patents referenced herein exist limitations in the methodologies that may significantly affect the outcome of the islet separation process.
The method of mechanical tissue dissociation with glass marbles, steel balls or other sufficiently dense and solid objects, either by hand or with mechanical shaking (Ricordi shaker), may cause tissue damage and trauma to islets resulting from excessive shear stress during the separation process. While repetitive mechanical agitation and contacting the pancreas with solid objects effects tissue disruption aiding enzymatic digestion, such current practices in standard isolation techniques are subjective, and vary between research facilities and transplantation centers.
Although sonication has been employed to aid pancreatic tissue digestion, one certain limitation in this technique is the 'static' water bath that the 'bagged' pancreas is placed in. Interestingly, this technique is continued until the pancreas appears 'cracked', yet, no mention of the internal temperature of the pancreas is noted. Static digestion by any method offers no means of forced-convective heat transfer to maintain a constant processing temperature (cooling during sonication) of the digesting pancreas or the resulting tissue suspension, by the process solution. It is possible that the internal temperature of a bagged pancreas in such a static system exceeds 37 to 40 degrees C., a temperature considered optimal for functional enzymatic digestion, yet, minimal in thermal shock and deactivation of islets due to elevated temperature. A statically digested pancreas in a bag offers no opportunity to maintain a controlled pancreatic processing temperature. This method presents no opportunity to dilute the tissue suspension, which precludes a real-time method to control, deactivate, or inhibit the digestive enzymes in the processing solution, during islet separation and processing, in the dilution and collection phase.
At the XVIII International Congress of the Transplantation Society, Aug. 27-Sep. 1, 2000 in Rome, Italy, advances in pancreatic islet cell transplantation procedures were reviewed and discussed. Existing limits of transplantation and novel approaches to achieving tolerance were evaluated. It was noted that success of recent transplantations (Edmonton Protocol) might certainly be due to the use of immunosuppression that was not toxic to beta cells. Avoiding the use of corticosteroids, induction therapy with anti-IL-2 antibody, and low-dose tacrolimus and sirolimus maintenance were undoubtedly key factors in non-rejection and continued islet tolerance. The quality of the purified islets also contributed to the success of the transplantations, yet, acquired by tedious and laborious manual methods lacking in process control methodology and neglecting important process variables. Current challenges were also assessed, specifically, the standardization of islet separation technology, and the need to development a standardized, reproducible, and automated method to separate and produce high-quality islet cells.
The background art is characterized by U.S. Pat. Nos. 5,273,904; 5,322,790; 5,377,790; 5,424,209; 5,612,188; 5,834,005; 5,837,738; 5,853,976; 5,879,939; 5,919,703; 5,919,775; and 5,952,215; and U.S. Patent Application No. 2004/0248077; the disclosures of which patents and application are incorporated by reference as if fully set forth herein. The background art is also characterized by the following articles, the disclosures of which are incorporated by reference as if fully set forth herein: Bond and Van Wart, Biochemistry, 23:3077, 1984, and Biochemistry, 23:3085-3091, 1984; D. Scharp, World Journal of Surgery 8:143-151, 1984; Linetsky et al., Transplant Proc., 30(2):345-346, March 1998; Vargas et al., Transplantation, 65(5): 722-727, Mar. 15, 1998; Jahr et al., J. Mol. Medicine (Berlin), 77(1):118-120, January 1999; and Eckhardt et al., J. Mol. Medicine (Berlin), 77(1):123-125, January 1999.
Presently there exists no process control method or device for islet separation that takes into account and crucial process variables that may be controlled to optimize islet isolation while standardizing and automating the islet separation process. Importantly, separation and processing variables have been omitted in background art methods and devices which compromise the reproducibility and repeatability of the islet separation process from location to location. Objectively applying advanced process control methodology disclosed herein and automating the islet isolation process with the process control technology and automated apparatus disclosed herein can optimize the islet separation process.

Automated apparatus for pancreatic islet isolation and processing


A degradable plastic film comprising film forming ethylene copolymers and lignin incorporated in the form of pulverulent powder having a grain diameter of about 1 to 5 microns. The films are homogeneous and possess a thickness of about 15 to 25 microns. The films may be made doubly decomposable by adding photoactive or oxidizing agents.

Photodegradable plastic films have also been known are known and more recently so-called biodegradable plastic films. The photodegradable plastic films are are obtained by introducing photoactive additives into a basic material which can be a polyolefin, for example. Generally, these additives are form by molecules containing oxygen and/or heavy metals the role of which is to initiate the formation of free radicals under the action of ultraviolet (UV) radiation; these radicals cause a rupture of the chains of the polymer and therefore make the polymer fragile, by making it weak and therefore mechanically degradable.
However, the use of certain additives which are strongly oxidizing causes the degradation to start immediately after the manufacture of the films, which has for consequence to reduce the storage capacity either of the master mixtures or of the films.
It should be noted that in agricultural uses of photodegradable films, portions of the films which are buried in the ground are protected from UV radiation and therefore not altered and not mechanically degradable, which has for its consequence to increase the scraps.
With respect to the biodegradable plastic films, they are obtained by the introduction of a so-called biodegradable organic filler such as starch which, consumed by the microorganisms, will make in turn the film fragile and therefore more easily degradable under the influence of the UV radiation.
The addition of starch as a consumable filler for microorganisms has consequences both concerning the fabrication of the film and in its mechanical properties; actually: starch is partially decomposed as soon as a temperature of 180.degree. C. is reached during the extrusion operation used in making the film; starch is not compatible with the polymers and therefore embrittles the films. Finally, the granulometry of the industrially available starch does not permit making films of small thickness. Yet, the thickness is an element of the cost price of the film, but also a parameter which governs the degradation speed of the film.

Degradable plastics film including lignin as active vegetable filler


A new and unique apple rootstock `Geneva 65` that is very dwarfing and resistant to crown rot and fire blight. The tree is also useful as a small ornamental flowering crab.

The present invention relates to a new and distinct cultivar of apple tree, Geneva 65, which we discovered in a test planting belonging to New York State Agricultural Experiment Station, Cornell University, `Geneva`, Ontario County, N.Y. This discovery is a product of the apple rootstock breeding program of the New York State Agricultural Experiment Station (`Station`).
In 1974, pollen was collected from a Beauty Crab apple tree and used to pollinate emasculated flowers of a Malling 27 (M.27) apple tree growing on Station grounds. The seeds were harvested from fruit produced from this cross and were stratified in November, 1974. After stratification, 198 germinating seeds were planted in a Station greenhouse in January, 1975. When the emerging seedlings were about 2.5 cm tall, we inoculated the soil with zoospores of 13 isolates of the fungus Phytophthora cactorum which is the causal agent of crown rot. The flat was flooded to mid-hypocotyl level of the seedlings, and kept at about 23.degree. C. for 7 days. All but 54 of the 198 seedlings were killed by this process. The surviving seedlings, when 10 to 15 cm tall, were inoculated in their shoot tips with about 10.sup.6 cells of isolate Ea273 of the bacterium Erwinia amylovora, the causal agent of the of the fire blight disease, using a 26 -gauge hypodermic syringe. Four subsequent inoculations with E. amylovora isolate Ea273 were made.
We selected 5 Erwinia amylovora-resistant seedlings and planted them as trench layers on the Station's Loomis Farm in April, 1976. Rooted liners were harvested in late fall 1979, 1980 and 1981 and were planted in the Station nursery in the springs of 1980, 1981 and 1982 respectively. Maiden trees of the cultivars `Northern Spy`, `Red Spy`, `Golden Delicious`, `Topred Delicious`, `Summerland McIntosh` and `Mutsu` were produced by budding onto `Geneva 65` liners. These trees were subsequently planted in trial orchards at the Station and at the United States Department of Agriculture Appalachian Fruit Research Station, Kearneysville, W.Va.; Hilltop Orchards, Hartford, Mich.; and Highmoor Farm, University of Maine, Monmouth, Me.
In these test plantings, trees on `Geneva 65` were about 20% smaller than trees on the Malling 9 rootstock, based on comparison with the check trees in the same test plantings. Trees on `Geneva 65` began flowering very early, usually the second year in the orchard; which was especially noteworthy for `Northern Spy` and `Red Spy` cultivars, which at Geneva, N.Y., normally begin fruiting in the 5th or 6th year on the precocity-inducing rootstock Malling-Merton 106. All of the cultivars that have been tested on `Geneva 65` have demonstrated high production efficiency, equal to that experienced with the Malling 9 rootstock.

Flowering crab apple/apple rootstock `Geneva 65`


In a word synchronous system for a word interleave method in a digital communication system, the word synchronous system includes a line demultiplexing unit that receives a higher order signal for demultiplexing lower order signals therefrom; a window generating unit operatively connected to the line demultiplexing unit for generating windows to demultiplex the lower order signals from the higher order signal in the line demultiplexing unit; and a plurality of sub-demultiplexing units operatively connected to the line demultiplexing unit for receiving corresponding lower order signals from the line demultiplexing unit; wherein the window generating unit receives any one of lower order signals from the line demultiplexing unit and performs the detection of frame synchronous words from said lower order signal, when the window generating unit detects any one of frame synchronous words, the window generating unit performs a bit shift operation for the window in such a way that the bits are immediately shifted to the frame synchronous word to obtain synchronization with the window.

1. Field of the Invention
The present invention relates to a word synchronous system for a word interleave method in a digital communication.
2. Description of the Related Art
As is well known, there are two methods for interleaving in a digital communication system, i.e., a bit interleave method and a word interleave method. The former means that lower order signals are multiplexed for every bit to form a higher order signal (so-called, bit multiplex). The latter means that the lower order signals are multiplexed for every word to form a higher order signal (so-called, word multiplex). The present invention is applied to a word interleave method.
In the word interleave method, the lower order signals are multiplexed to the higher order signal in a transmitting side and the higher order signal is sent to a receiving side. In the receiving side, the higher order signal is demultiplexed to the lower order signals.
In the receiving side, it is necessary to obtain word synchronization when demultiplexing the higher order signal. The present invention relates to a word synchronous system for the word interleave method in the reception side.

Demultiplexing system for word interleaved higher order signals in a digital communication system


Hair growth is affected by topical application of a boron containing compounds/complexes in which a central tetrahedral boron atom is covalently bound to four ligands. At least one of the ligands preferably includes an oxygen, nitrogen, carbon, or sulfur atom, and preferably all four ligands include at least one such atom. Preferred ligands are saccharides and amino acids, including fructose, sorbitol, mannitol, xylitol, sorbose, serine and threonine. Especially preferred ligands have a conformation with at least two hydroxyl groups, or one hydroxyl group and one amino group in a 1,2- and a 1,3- position relative to each other, providing a high association constant in the range of about 3,000 and about 20,000. The compounds/complexes are preferably provided in formulations which provide good transdermal delivery, including appropriate solvent systems, microemulsions, liposomes.

Biological Activity and Use of Boron Compounds
Boron compounds are known to show a variety of different biological activities. Very often, boron compounds show enzyme inhibitory activity, and thus boron compounds can inhibit a number of enzymes alone or in a mixture with various co-inhibitors. For example, borates inhibit L-amino acid oxidase in a mixture with butanedione by interacting with the arginine residue in the active site. (Christman M F, Cardenas J M: Experientia 38 (5): 537-538 (1982)).
Similarly, borates and butanedione inhibit citrate/isocitrate-hydro-lyase, EC 220.127.116.11, again by interacting with the arginine residue from the active site. (Gawron O, Jones L: Biochem Biophys Acta 484 (2): 453-464 (1977)). Also, 2,3-butanedione or 1,2-cyclohexanedione in the presence of borates interact specifically with the guanidino group from arginine, and this fact was used for determination of arginine residues in the active site of the examined enzymes. In this way Dietl, T. and Tschesche, H. (Hoppe Seylers Z Physiol Chem: 357 (5): 657-665 (1976)) proved arginine residue is present in the active site of proteinases.
Borates (at low concentration) are also known to inhibit glyceraldehyde-3-phosphate dehydrogenase from human, pig and rabbit muscle. However, in greater concentration (above 6 mM) borates inhibit esterase and acetylphosphatase activities. (Wolny M: Eur J Biochem 80 (2): 551-556 (1977)).
An interesting biological activity of borates was noticed in the case of palytoxin induction of the histamine release from rat mast cells. In the presence of borates the activity of palytoxin was increased ten times (Chhatwal G S, Ahnert-Hilger G, Beress l, Habermann E: Int Arch Allergy Appl Immunol 68 (2): 97-100 (1982)).
Borates inhibit methylation of catechol estrogen and pyrocatechol by catechol-O-methyltransferase (Beattie J H, Weersink E: J Inorg Biochem 46 (3): 153-160 (1992)).
Several naturally occurring antibiotics contain boron as an essential structural element (such as boromycin, an anti-HIV antibiotic (Kohno J, et al: Biosci Biotechnol Biochem (Japan) 60(6), 1036-7 (1996), or tetralons, new boron-containing antibiotics from a myxobacterium, Sorangium cellulosum (Irschik H, Schummer D, Gerth K, Hofle G, Reichenbach H: J Antibiot (Tokyo) (Japan), 48 (1), 26-30 (1995)).
Borates and some of their organic complexes are experimentally used in surgery as agents which promote healing of open wounds (Humzah M D, Marshall J, Breach N M: J R Coll Surg Edinb (England) 41(4), 269-70 (1996); McCowan M, Aitken F: J Wound Care (England), 6(5), 248-249 (1997); Bliss M R: J Wound Care (England) 6(5), 248-249 (1997)).
Larvicidal effects of ingestion of boric acid and disodium octaborate tetrahydrate by cat fleas was recently described by Hinkle N C, Koehler P G, and Patterson R S in J Med Entomol (United States), July 1995, 32(4), p 424-7.
Some specific organoboron compounds (such as cyanotriphenylborate) were shown to be subtype-specific blockers of glycine receptor chloride channels (Rundstrom N, Schmieden V, Betz H, Bormann J, Langosch D: Proc Natl Acad Sci USA (United States), 91(19), 8950-4 (1994)).
A very important biological behavior of certain boron compounds is their interaction with Ca-metabolism. Namely, it has been noticed (Benderdour M, Hess K, Dzondo-Gadet M, Dousset B: Biochem Biophys Res Commun 234 (1), 263-8 (1997)) that boric acid itself, acting upon a pelvic cartilage of chick embryo, induced release of proteoglycans, collagen and other proteins, but at the same time strongly decreased their intracellular synthesis. However, surprisingly enough, boric acid in the presence of a great molar excess of glucose did not decrease intracellular biosynthesis of proteins, but still induced efficiently their intensive secretion. The effect can not be ascribed to a boron toxicity, since the cell membranes were intact (observed by electronic microscopy) and the cells were secretory. It was assumed that boron interacted actively with Ca-metabolism (see, in addition to this article, Nielsen F, Muller L, Galigher S: J Trace Elem Exp Med 3, 45-54 (1990); Nielsen F H: FASEB 5, 2661-7 (1991)). Benderdour et al postulated that boric acid or its glucose complex can inhibit serine/threonine phosphatases.
Specific biological calcium-boron interaction is also supported by a work of T. Maruyama et al (J Biochem (Tokyo), 122(3), 498-505 (1997)) who showed that 2-aminoethoxydiphenyl borate (2 APB) inhibited Ins (1,4,5) P3-induced Ca2+ release from rat cerebellar microsomal preparations. At the same time, addition of 2 APB to the extracellular environment inhibited the cytosolic Ca2+ rise in intact cells such as human platelets and neutrophiles stimulated by thrombin or leukotriene B4 (LTB4).
Use Of Enzyme Inhibitors in the Negative Control of Hair Growth
Regarding the use of enzyme inhibitors for control of hair growth, there are several approaches described in the corresponding patent literature, all of which have nothing to do with boron. Patents describing an induction of hair re-growth are rather numerous and will not be discussed here. On the other hand, patents dealing with hair growth reduction, by inhibiting/targeting the key-enzymes which support/promote the hair growth, are not that numerous, but are of a particular relevance to our discovery.
For obvious reasons, in this overview of hair growth reduction, we ignore both classical depilation methods (using thio-glycolates, e.g.) and physical/mechanical methods of hair removal (such as laser treatment, e.g.).
In U.S. Pat. No. 4,885,289 (to M M Breuer et al, issued Dec. 5, 1989), a topical application of a steroid 5.alpha.-reductase inhibitor reduces male beard growth.
In U.S. Pat. No. 5,095,007 (to G S Ahluwalia, issued Mar. 10, 1992), the process of reducing the rate and altering the character of mammalian hair growth was described by topical application of a composition containing an inhibitor of adenylosuccinate synthetase.
In U.S. Pat. No. 5,096,911 (to G S Ahluwalia et al, issued Mar. 17, 1992) a reducing rate of mammalian hair growth was achieved by a topical application of a composition containing an inhibitor of gamma-glutamyl transpeptidase.
In U.S. Pat. No. 5,132,293 (to D Shander et al, issued Jul. 21, 1992) hair growth reduction was observed by topically applying an ornithine decarboxylase inhibitor.
In U.S. Pat. No. 5,143,925 (to D Shander and M G Funkhouser, issued Sep. 1, 1992) hair growth reduction was achieved by topical treatment of a mammalian skin with an inhibitor of the enzyme transglutaminase.
In U.S. Pat. No. 5,455,234 (to G S Ahluwalia and D Shander, issued Oct. 3, 1995), mammalian hair growth is reduced by applying to the skin an inhibitor of a cysteine synthesis pathway enzyme.
In U.S. Pat. No. 5,474,763 (to D Shander and G M Funkhouser, issued Dec. 12, 1995) mammalian hair growth is reduced by a topical application to the skin an inhibitor of ornithine aminotransferase.
In U.S. Pat. No. 5,468,476 (to G S Ahluwalia et al, issued Nov. 21, 1995), applying to the skin an inhibitor of nitric oxide synthetase reduced mammalian hair growth.
Finally, in U.S. Pat. No. 5,652,273 (to J. Henry et al, issued Jul. 29, 1997) a method of reducing hair growth in a mammal was described by applying a suppressor of the metabolic pathway for the conversion of glucose to acetyl-CoA.

Boron compounds/complexes to control hair growth, and methods of use


Processes for the preparation of high purity alkyl esters of polyene macrolide antibiotics are disclosed. The processes involve treating an amphoteric polyene macrolide antibiotic with an aldehyde to yield the corresponding Schiff base which is soluble in the reaction medium. The solution is then treated with an alkylating agent in the presence of a hindered tertiary amine as acid acceptor to yield the alkyl ester of the polyene macrolide antibiotic in the form of its Schiff base derivative. Contacting this derivative with water converts the Schiff base derivative to the desired alkyl ester of the polyene macrolide antibiotic which is recovered from the reaction medium.

This invention relates to alkyl esters of polyene macrolide antibiotics and to convenient and safe synthesis thereof by methods suitable for large scale production.
U.S. Pat. No. 3,945,993 to Schaffner et al. relates to the preparation of esters of Amphotericin B and other amphoteric polyene macrolides by dissolving the polyene macrolide in methyl sulfoxide and diluting with tetrahydrofuran. The resulting suspension is treated with diazomethane to produce the methyl ester. The ester product is then recovered from the reaction mixture by precipitation with ethyl ether.
U.S. Pat. No. 4,035,568, also to Schaffner et al., relates to processes for making Amphotericin B derivatives using diazomethane or diazapropane.
Belgian Patent No. 802,512 relates to another method for synthesis of the methyl ester of Amphotericin B. Aqueous ammonium hydroxide is added to a solution of Amphotericin B in methyl sulfoxide to approximately pH 10. Treatment of this mixture with diazomethane yields the methyl ester.
U.S. Pat. No. 4,035,567 describes another procedure for the preparation of Amphotericin B methyl ester. Amphotericin B is mixed with either dimethylformamide (DMF) or hexamethylphosphoric triamide (HMPA) for a specific time period. Ammonium hydroxide is then added to raise the pH of the mixture above 9 with DMF or above 10 with HMPA. Diazomethane is then added in each case to form the methyl ester.
The use of diazomethane with unprotected Amphotericin B or other amphoteric polyene macrolides to produce the corresponding methyl esters is most often associated with the formation of undesired by-products. These often consist of compounds wherein methylation has occurred at sites in the molecule in addition to the carboxyl function.
U.S. Pat. No. 4,235,993 describes an attempt to limit the formation of these polymethylated Amphotericin B derivatives. Included are several synthetic steps during which the intermediates, namely N-benzylidine Amphotericin B and its methyl ester, are formed. Amphotericin B is dissolved in equal parts of DMF and dimethyl-sulfoxide (DMSO), and benzaldehyde is then added to form the Schiff base, N-benzylidine Amphotericin B. Treatment of this intermediate with diazomethane in tetrahydrofuran (THF) yields the intermediate product, N-benzylidine Amphotericin B methyl ester. Treatment of this intermediate with acids in aqueous medium hydrolyzes the Schiff base and produces the water-soluble Amphotericin B methyl ester salt.
Most of the available procedures to protect an amine block the amino function as an amide or carbamate (see T. W. Greene, "Protecting Groups in Organic Synthesis", J. Wiley Publ., New York, 1981). The FMOC (fluorenylmethylcarbonyl) group has been employed to protect the amino group of Amphotericin B (M. J. Driver et. al., Tetrahedron Letters, 33, 4357-4360 (1992). Diazomethane or methyl iodide with diisopropylethylamine is then utilized to esterify the carboxyl group and the FMOC protecting group is removed in a second reaction. It is unexpected that use of the Schiff base to protect the amino group is possible in the esterification with an alkylating agent since it might be expected that an alkylating agent such as methyl iodide or dimethyl sulfate would alkylate the imino nitrogen forming an N-methyl compound. The major additional advantages of using the Schiff base protecting group are solubilizing of the Amphotericin B by disruption of its amphoteric character and ease of removal of the protecting group by contact with water under relatively mild conditions which do not effect the sensitive groups in the polyene molecule. An additional benefit is the steric interaction of the Schiff base which prevents alkylation of the hydroxyl groups on the glycosamine function.
Amphotericin B is a polyene macrolide antibiotic useful in a variety of applications including human treatment of systemic fungal diseases and agricultural treatment of fungal plant infections. Amphotericin B and its methyl ester have also been shown to have a broad spectrum of antiviral and anticancer activity. The structure of Amphotericin B (AMB) and its methyl ester (AME) are illustrated below: ##STR1## AMPHOTERICIN B: R.dbd.H AMPHOTERICIN B METHYL ESTER: R.dbd.CH.sub.3

Polyene macrolide schiff bases, their alkyl esters and processes for preparing polyene macrolide alkyl ester salts thereof


A vascular plug includes a plurality of cells which extend from a front face of the plug towards a distal end of the plug. The cells form at least a periphery of the plug and are in the preferred embodiment closed at their distal ends. The cells may form a central chamber to the plug or may extend across the entirety of the front face of the plug. The cells will fill with blood from the patient's vessel, to inflate the plug and create a barrier to fluid flow. Static blood within the plug will clot over time, creating enhanced occlusion. The plug can also be configured as a vascular filter.

Vascular plugs have been known for a number of years. Many are in the form of a device which is implanted within a vessel of a patient and have a structure which closes off the vessel so as to occlude blood flow. Occluders of the plug type are preferable over more traditional forms of occlusion, such as vascular constrictors, which generally require an invasive medical procedure. Vascular plugs, on the other hand, can be deployed endoluminally in a significantly faster and less traumatic medical intervention.
Vascular plugs may be designed or used to provide temporary occlusion, for example to be effective only for the duration of a medical procedure or during a period of treatment. Occlusion may also be permanent, in which case the occluder will be left within the patient indefinitely.
There are two primary types of occluding vascular plug. The first promotes embolization within the vessel, for instance by slowing the flow of blood through the device, in some cases with the addition of embolization promoters. Such devices do not produce immediate occlusion of the vessel as they rely upon the formation of sufficient blood clotting to act as the occluding barrier. Thrombosis in sufficient amount to occlude can take hours, days or even weeks in some instances.
Another type of vascular plug has an impervious element, typically a membrane, which extends across the diameter of the vessel to create an instantaneous barrier to blood flow. In many cases such immediate occlusion is preferable. However, it is difficult to counter reliably the full force of the blood flow, leading to risk of migration of the device, loss of positional orientation, or failure to achieve a full seal against the vessel wall and thus in failure of the device. Furthermore, some such devices can fail to deploy properly in the vessel, leading them to being ineffective from the start.
Some examples of known vascular plugs can be found in U.S. Pat. No. 5,645,558, U.S. Pat. No. 5,683,411, U.S. Pat. No. 6,063,113, US-2008/262,518, US-2009/099,647 and WO-10/085,344.


The present invention provides a silicone gel composition for use in sealing and filling of electrical and electronic parts, which are characterized by the fact that when said composition is cured, said composition forms a silicone gel in which the loss elastic modulus at a temperature of 25.degree. C. and a shear frequency of 0.1 Hz is 1.0.times.10.sup.2 to 1.0.times.10.sup.4 Pa, and in which the complex elastic modulus is 1.0.times.10.sup.5 Pa or less, and a silicone gel which is characterized by the fact that in a silicone gel which seals or fills electrical or electronic parts, the loss elastic modulus of this silicone gel at a temperature of 25.degree. C. and a shear frequency of 0.1 Hz is 1.0.times.10.sup.2 to 1.0.times.10.sup.4 Pa, and the complex elastic modulus is 1.0.times.10.sup.5 Pa or less.

When cured, silicone gel compositions can form silicone gels which have good stress-relieving characteristics, electrical characteristics, heat resistance and weather resistance. Accordingly, such silicone gel compositions are widely used as sealing agents and filling agents in electrical and electronic parts (see Japanese Patent Application Kokai No. 9-204259, Japanese Patent Application Kokai No. 61-48945, and Japanese Patent Application Kokai No. 62-104145). Furthermore, examples of such silicone gel compositions include silicone gel compositions which consist of a vinyl-group-containing organopolysiloxane which has a branched structure and which has a viscosity of 10 to 10,000 centistokes at 25.degree. C., a linear organopolysiloxane which contains hydrogen atoms bonded to silicon atoms, and a hydrosilylation reaction catalyst (see Japanese Patent Application Kokai No. 48-17847); silicone gel compositions which consist of a vinyl-group-containing organopolysiloxane which has a branched structure, an organopolysiloxane which contains hydrogen atoms bonded to silicon atoms, and a hydrosilylation reaction catalyst (see Japanese Patent Application Kokai No. 58-7452); and silicone gel compositions which consist of a vinyl-group-containing organopolysiloxane which has a branched structure and which has a viscosity of 20 to 10,000 centistokes at 25.degree. C., a linear organopolysiloxane in which both ends of the molecular chains are closed by vinyl groups, a linear organopolysiloxane which contains hydrogen atoms bonded to silicon atoms only at both ends of the molecular chains, and a hydrosilylation reaction catalyst (see Japanese Patent Application Kokoku No. 3-19269).
However, when electrical or electronic parts which have a complicated structure are sealed or filled by means of such silicone gel compositions, gas bubbles and cracks are formed in the sealing silicone gel as a result of the heat cycle, so that the reliability of the electrical or electronic parts drops. Furthermore, it has been found that the formation of gas bubbles and cracks in silicone gels sealing or filling such electrical or electronic parts is conspicuous in the case of electrical or electronic parts in which there are narrow gaps between adjacent electrodes, adjacent electrical elements or electrical elements and packages, etc., and electrical or electronic parts in which it is difficult for such structures to conform to the expansion or contraction of the silicone gel.

Silicone gel composition and silicone gel for use in sealing and filling of electrical and electronic parts


Embodiments of the present invention provide for automated client-computer connection to NAS objects within a networked computer system. In certain embodiments of the present invention, a master-agent process is continuously executed on one or more computers of the networked computer system. The master agent is connected to, manages, and exchanges information with a NAS-object repository. When a client computer is booted, or reinitializes, a client agent running on a client computer communicates with the master agent in order to receive at least one executable code block for each NAS object designated for access by the client computer. By executing these executable code blocks, the client computer can automatically connect to the NAS objects. In certain embodiments of the present invention, the master agent also provides an administration interface that allows a system administrator to configure a networked computer environment with respect to client computers and NAS objects.

In early computer systems, data-storage devices were either peripheral devices directly connected to computer systems or were internal components of the computer systems. Later, following the advent of computer networking, computer systems were provided the ability to access remote data-storage components through network communications. In general, these remote data-storage components are directly connected to remote computer systems, and access to the remote data-storage systems involves exchanging data with the remote computer systems to which they are attached. The remote computer systems essentially operate as data and file servers. Still more recently, independent, autonomous data-storage devices have been developed for direct access by client computers. These autonomous data-storage devices often store data redundantly, in order to provide fault tolerance, and may be implemented with redundant components in order to provide both hardware fault tolerance and high availability. One class of autonomous data-storage devices includes devices referred to as "network-attached storage devices" ("NAS devices"). NAS devices are generally implemented using relatively stripped-down operating systems to provide remotely-stored file systems for computer systems, referred to as "client computers," that access the NAS devices via network communications. NAS devices may each provide one or more NAS objects, each NAS object representing, to an accessing client computer, the root directory of a file system. NAS devices may also implement data bases, code repositories, and many other types of networked-attached data-serving systems. NAS devices and NAS objects are relatively inexpensive, are relatively straightforwardly incorporated into networked computer environments, and provide flexible, easily augmented data storage for a networked computer environment. However, with the proliferation of NAS devices and NAS objects within many networked computer systems, configuration and management of NAS-object/client-computer connections has become a significant administrative overhead. For this reason, designers, manufacturers, vendors, and users of NAS devices and NAS objects, and of computer systems that access NAS devices and NAS objects, have recognized the need for a unified management and maintenance tool for networked computer environments that include NAS devices and NAS objects.

Method and system for configuration and management of client access to network-attached-storage

Hewlett-Packard Development Company, L.P.


The present invention relates to a method for diagnosing glioma by comparing the protein location of an individual to be diagnosed with the normal control nerve cells. More particularly, the present invention relates to a method for diagnosing glioma including determining that an individual has glioma when the expression level of GFRα4 in the endoplasmic reticulum is higher than that in the plasma membrane, and a method for screening a therapeutic agent for glioma. In the diagnostic method of the present invention, the protein expression levels in particular subcellular locations are compared, thereby accurately diagnosing glioma, diagnosing progression of glioma, and predicting prognosis after glioma surgery.

1. Field of the Invention
The present invention relates to a method for diagnosing glioma by comparing the protein locations in an individual to be diagnosed with those of the normal control nerve cells. More particularly, the present invention relates to a method for diagnosing glioma comprising determining that an individual has glioma or of predicting prognosis after surgery of glioma when the expression level of GFRα4 in the endoplasmic reticulum is higher than that in the plasma membrane, and a method for screening a therapeutic agent for glioma. Further, the present invention relates to a method for diagnosing glioma or for predicting prognosis after surgery of glioma based on the number of GFRα4 and PSPN interactions.
2. Description of the Related Art
A change in the subcellular location of a protein is fundamental to cell function and regulatory control. Generally, protein location can be governed by signal peptides, which convey proteins to the specific organelle. It is also an important regulatory mechanism, as signal peptides can be modified by carrier proteins that recognize a particular pattern of modifications after translation of mRNA into peptide. For example, STAT3 (signal transducer and activator of transcription 3) is phosphorylated by various cytokines and growth signals, resulting in its relocation to the nucleus, where it serves as a strong DNA-binding transcriptional activator. Inappropriate phosphorylation and relocation of STAT3 are known to promote oncogenesis through abnormal cell cycle progression, angiogenesis, and invasion of tissue. Changes in protein location are also associated with genetic disorders. For instance, in Zellweger syndrome, relocation of peroxisomal proteins leads to dysfunctional fatty acid oxidation.
Therefore, functional changes of cells can be predicted through accurate identification of changes in the subcellular locations of proteins and the type of neighboring proteins.
Meanwhile, there are two types of brain tumors; primary brain tumors that originate in the brain itself and metastatic brain tumors that spread from other organs. Primary brain tumors can be further divided into two types of tumors—benign and malignant. Even if primary brain tumors are benign, benign tumors can compress normal parts of the brain, causing severe nerve dysfunction. In many cases, benign brain tumors are also difficult to treat, like malignant tumors. Each year, over 190,000 people in the United States and 10,000 people in Canada are diagnosed with a primary or metastatic brain tumor. Brain tumors are the leading cause of solid cancer death in children under the age of 20. Although, brain tumors can be benign, the survival rate is lower than that of breast cancer. The incidence of metastatic brain tumors is estimated to be 10-15%, but it is growing with the increasing survival rate of tumor patients. At present, the prevalence rate in the United States is estimated to be 29.5 per 100,000, and glioma accounts for 50% of all brain tumors. Glial cells exist between the neurons and between the neuron and the blood vessel, and function to supply nutrients or oxygen to neurons. Many gliomas are malignant, and classified by the cell type or their features.
Gliomas are the most common type of primary brain tumor, and are associated with poor prognosis. High-grade astrocytomas including glioblastoma multiforme (GBM) and anaplastic astrocytoma (AA) are the most common intrinsic brain tumor m adults. While there has been progress in understanding the molecular genetics of high-grade astrocytomas, the cell type(s) of origin are still uncertain, and the molecular determinants of the disease's aggressiveness are not well understood. A better understanding of the cellular origin and molecular pathogenesis of these tumors may identify new targets for treatment of these neoplasms that are nearly uniformly fatal.
The grading of tumors is often critical to obtain an accurate diagnosis and prognosis of disease progression, and glioma is no exception. Decades of experience have led to a system of diagnosis of gliomas based on histology. Gliomas are histologically defined by whether they exhibit primarily astrocytic or oligodendroglial morphology. Gliomas are graded by cellularity, nuclear atypia, necrosis, mitotic figures, and micro-vascular proliferation, and all features associated with biologically aggressive behavior. This system of diagnosis has been developed over decades of clinical experience with gliomas and has now become the cornerstone of neuro-oncology [Kleihues, P. et al., World Health Organization ("WHO") classification of tumors, Cancer 88: 2887 (2000)].
Satisfactory studies to develop an early, accurate and simple diagnosis of glioma with poor prognosis have not been conducted yet. Accordingly, the present inventors have made many efforts to develop an accurate diagnostic method for glioma. As a result, they found that locations of particular proteins and the number of protein-protein interactions differ between normal cells and glioma cells, which were visualized by FCCS (fluorescence cross-correlation spectroscopy), and glioma can be diagnosed by comparing the expression levels in the subcellular locations between normal cells and glioma cells through Western blotting, thereby completing the present invention.

Method for diagnosing glioma and screening for the therapeutics of glioma through identifying protein relocation

AJOU UNIVERSITY INDUSTRY-ACADEMIC COOPERATION FOUNDATION