A hub cap (10) is fitted to the outer end of a wheel hub (11) containing a wheel bearing (14) to seal the outer end of the hub (11). The hub cap (10) has a cylindrical housing (16) which is provided with a transparent outer end wall (17) to permit the level of lubrication around the bearing (14) to be ascertained visually. The cylindrical housing (16) has an aperture within which a plug (22) is fitted. The plug (22) has a flexible diaphragm (21) which deforms to accommodate pressure changes within the hub cap (10). The hub cap (10) is particularly suitable for wheel bearings of trailers, such as boat trailers.

This invention relates to a hub cap assembly for a wheel bearing. The invention is particularly, but not solely, directed to a hub cap for a wheel bearing on a boat trailer.
Hub caps are normally placed on wheel bearings to prevent ingress of dirt, dust, water and other contaminants to the bearing, and thereby prolong the life of the wheel bearing. The hub cap also serves to retain lubricating grease in the bearing cavity.
Wheel bearing assemblies on trailers are lubricated by hand packing grease into the bearings at the time of assembly. Thereafter, wheel bearings, particularly those on trailers, are seldom checked (especially as trailers do not normally undergo regular servicing). Hence, the loss of lubricating grease from the wheel bearing may go unnoticed until the bearing fails. (With loss of lubrication, the bearing runs extremely hot, particularly at highway speeds. The bearing materials are likely to fail at high temperatures, with possibly catastrophic results if the vehicle is travelling at high speed).
In most wheel assemblies, there is little, if any, provision for the permanent lubrication of the inboard or rear seal of the bearing. Consequently, many rear seals will dry up and/or burn out in a short period of time in the absence of lubrication, thereby creating opportunity for water to enter the bearing.
It is known to use sealed hub caps on wheel bearings to prevent loss of lubrication. However, the interior of a wheel bearing is subject to a wide range of temperatures. From ambient temperature when stationary, the temperature inside the wheel bearing can increase quite quickly to over 90xc2x0 C. when the vehicle is travelling at highway speeds. With such increase in temperature, the resultant pressure increase within the sealed bearing can cause the inboard grease seal to blow out, resulting in loss of lubrication.
Vented hub caps are sometimes used to accommodate temperature increases in the bearing chamber. By venting the hub cap to the atmosphere, the pressure within the bearing chamber is maintained at or near atmospheric pressure.
Although vented hub caps are able to handle pressure changes due to variations in the temperature of the bearing, they give rise to particular problems when subjected to rapid temperature changes. For example, wheel bearings on boat trailers are usually at an elevated temperature after a road trip to a boat launching ramp. When the hot wheel bearings are submerged in the water during the boat launching procedure, the temperature of the bearing chamber is reduced rapidly, leading to a sudden pressure drop or partial vacuum in the bearing chamber. As a result, water and other contaminants are sucked in through the hub cap vents and/or the inboard seal.
Due to the substantially closed configuration of the bearing chamber, such water can remain in the bearing for a considerable period of time. This leads to rust, particular if the bearing is unused for extended periods as is common for boat trailers. The rust problem is exacerbated if the water is salt water.
It is an object of the present invention to provide an improved hub cap for a wheel bearing which overcomes or ameliorates at least some of the above described disadvantages, or which at least provides the consumer with a useful choice.
The invention provides a hub cap for a wheel bearing. The hub cap is in the form of a cup-like housing adapted to be fitted to a wheel hub containing the bearing. The cup-like housing preferably has at least one transparent portion to enable the level of lubrication in the housing to be ascertained visually.
Typically, the cup-like housing is of cylindrical form, and the transparent portion is a circular glass end wall sealingly fitted to the cylindrical housing.
Advantageously, the hub cap is a sealed or closed hub cap, rather than a vented hub cap. The closed construction of the hub cap prevents ingress of contaminants to the wheel housing.
More preferably, the hub cap includes at least one flexible portion adapted to accommodate pressure changes within the hub cap housing.
In the preferred embodiment, the hub cap includes a pressure equalisation device having a membrane sealingly located in an aperture in the cup-like housing. The inner side of the membrane is subject to pressure within the housing, while the outer side of the membrane is vented to the atmosphere. The flexible membrane can deform to substantially equalise the pressure within the hub cap housing with the outside pressure, while maintaining the sealed nature of the hub cap.
A filler plug or similar device is suitable provided on the housing to allow lubricating material to be fed to the wheel bearing via the hub cap.
Preferably the lubricating material is oil. The oil not only serves to lubricate the bearings, but also protects the rear seal from drying out. Since the rear seal is permanently lubricated by the oil, it remains waterproof. As the front hub cap is also waterproof, the complete wheel bearing is sealed, and suitable for marine applications.
The hub cap is particularly suitable for trailers, such as boat trailers.
In order that the invention may be more fully understood and put into practice, a preferred embodiment thereof will now be described with reference to the accompanying drawings.


An image-capturing apparatus includes an image-capturing unit configured to capture image data of a subject and to store the captured image data in an image-capturing operation; a speed detector configured to detect speed information; and a controller configured to control the image-capturing unit so that, in an automatic image-capturing process that is not based on a shutter operation of a user, a distance moved by the image-capturing apparatus is computed on the basis of information from the speed detector, and the image-capturing operation is performed in response to the fact that a computation result indicating that the image-capturing apparatus has moved a predetermined distance is obtained.

1. Field of the Invention
The present invention relates to an image-capturing apparatus and an image-capturing control method. More particularly, the present invention relates to an image-capturing apparatus for performing drive log image capturing and life log image capturing as automatic image capturing.
2. Description of the Related Art
For example, as a drive log camera, a camera which is disposed inside an automobile has been considered, in which still images are captured periodically, and thereby a user records scenery in the traveling direction and inside the car as image data while driving the car. Furthermore, in addition to image capturing of still images, a camera for capturing moving images has also been considered. Furthermore, a camera of a type, which is also called a life log camera or a life slice camera, which is worn by a user himself/herself, and in which image capturing is periodically performed to capture an activity history of the user, has also been considered.
By using the drive log camera and the life log camera, it is possible to record, as image data, the activity history and memories of the user when the user moves by an automobile, on foot, or the like.
In Japanese Unexamined Patent Application Publication No. 2007-109049, an apparatus is proposed in which images of the surroundings of a user's vehicle are captured using a camera disposed in the user's vehicle, an edge extraction process is performed on camera images when the user's vehicle is stopped and on camera images when the user's vehicle starts moving in order to detect an object. When an object is detected, the camera image at the departure time is displayed on a display device, and when an object is not detected, the camera image at the departure time is not displayed.

Image-capturing apparatus and image-capturing method for performing drive log image capturing and life log image capturing as automatic image capturing


A polarizing plate with retardation layers of the present invention includes a polarizer, a first retardation layer, and a second retardation layer in the staled order. The polarizer and the lust retardation layer are bonded to each other via a first adhesive layer, the first retardation layer and the second retardation layer are bonded to each other via a second adhesive layer, the first retardation layer and the second retardation layer each have a thickness of 5 μm or less, and the second adhesive layer has an average refractive index of 1.55 or more, and a difference between the average refractive index of the second adhesive layer and an average refractive index of the first retardation layer, and a difference between the average refractive index of the second adhesive layer and an average refractive index of the second retardation layer are each less than 0.08.

In order that poor visibility due to ambient light reflection or background reflection in the display screen of a display apparatus may be alleviated, a display apparatus in which a circularly polarizing plate is arranged on the viewer side of a display panel has been known. In each of Patent Literatures 1 and 2, there are proposals of a polarizing plate that has achieved an excellent reflection hue in an oblique direction through the reduction of the reflection of incident light from the oblique direction in black display, and a display apparatus including the polarizing plate.

Polarizing plate with phase difference layers, and organic EL display device


Described is a device for machine tools or measuring apparatus for detecting the spatial position of a carriage movable in a coordinate axis along a guide with respect to a reference standard which is designed as a rectangular plate extending parallel to the guide of the carriage. Two opposed, parallel surfaces of the reference standard carry each a two-dimensional line grating. A position measuring system serves the function of determining continuously the spatial position of a support member fixedly connectible with the carriage. The position measuring system includes three optical incremental reading heads and one distance sensor. The support member is arranged on the movable carriage such as to prevent the support member from contacting the reference standard over the entire length of the travel while at the same time detection is being performed. Owing to the arrangement of the three reading heads and the distance sensor at accurately defined positions on the support member it is possible to determine the location and the spatial position of the support member and hence of the carriage connected therewith.

From DE 31 50 977 A1 methods and a device are known for determining and correcting guide defects of guided machine parts, the device corresponding to the device initially referred to. In a first method, relevant guide defects of a measuring machine are determined and approximated by correcting functions stored in the machine's computing unit. The incorrect results of the coordinate measuring device are then corrected in subsequent measurements by means of the correcting functions. In a second method, additional measuring devices are attached to the movable parts of the measuring machine to measure the distance to reference lines extending in the direction of displacement. With these measuring devices the guide defects are detected continuously during the measurement operation. The computing unit of the measuring machine uses the output signals of the additional measuring devices in order to correct the incorrect results of the coordinate measuring device. In a third method, the existing guide surfaces of the machine serve as reference lines, which is a less complex task, and the deviations once established by measurement against a linearity standard are stored in the form of an approximation function and used for permanent correction of the measurement values of the additional measuring devices. In this third method, which is a combination of the two methods first referred to, the tips of additional probes slide on the guide surfaces. To implement the two first-identified methods, use is made of a prismatic reference standard that extends parallel to the guide of a carriage. The reference standard carries on a first and on a second surface line gratings, one of which is two-dimensional. A position measuring system serves to determine the spatial position of a support member fixedly connected to the carriage, which support member has reading heads fitted to it and is guided on the reference standard. The reading heads or the support member are placed directly on surfaces of the reference standard. Such a measuring system which measures the displacement in a coordinate and detects at the same time the influence of any guide defects, is suitable, for example, for attachment to the guides of a measuring or processing machine with the aim to enhance its positioning accuracy considerably. In the first method it is assumed that the guide defects are constant and, once measured, can be stored as an approximation function to be considered in subsequent measurements. In the second method guide defects are measured continuously, yet only the relevant ones because of the increased complexity involved. The third method requires the use of an approximation function and the permanent correction of the measurement values of the additional measuring devices. In all the methods, the reference standard serves as a mechanical guide for the support member, which is always a disadvantage.
From DE 43 45 094 C2 a shape measuring machine is known, which includes a reference system for path correction on guideways that is decoupled from the machine's guiding means and control devices and comprises dimensionally accurate elongate standards disposed in parallel alignment to the individual coordinate axes of slidable carriages and adapted to be scanned continuously by parts movable on the guiding means. The reference system is not exposed to major forces and is constituted so as to have a geometry which is long-term stable with little sensitivity to temperature. While this known shape measuring machine distinguishes itself by displaying good guiding relationships for the slidable carriages, the complexity involved is considerable, in terms of both apparatus and measurement expenditure. The reference system is comprised of three standards, each formed by profiled rails of rectangular cross-section carrying scanning tracks on two adjacent lateral surfaces. The first standard is mounted on the machine bed. The second standard is attached to the end of a vertical column in addition to having at one end angle brackets embracing the scanning tracks of the first standard, so that the second standard is coupled to the first standard. Correspondingly, the third standard is coupled to the second standard. Provided at each of the two coupling locations between the three standards are several sensors which detect any relative movement between two standards at their coupling location in terms of their position and direction. The detected values are fed to a computing unit calculating therefrom corresponding correction values for the measurement result or for the spatial position of the probe element. This construction aims to enable the known shape measuring machine to exhibit an improved dynamic behavior and reduced non-productive times and durations of measurement as compared with a shape measuring machine with an extremely rigid machine bed, which is frequently manufactured from granite and supports, through a sliding carriage, the vertical column, which in turn is either a solid or heavy cast or steel welded construction.
From WO 99/17073 a device is known for the detection of six components of the relative motion of two bodies with one primarily two-dimensional translational basic motion. The bodies are formed of a plate provided with a two-dimensional optical grating and of an element having a plane surface parallel to the plate and including several optical gratings as reading head. The element is approximated to the plate in such fashion that the optical gratings enable detection of relative displacements, parallel to the plate, in the X and Y directions through evaluation of the intensity variations of the reflected light. To detect the distance between the element and the plate, provision is made for at least three distance sensing devices which are of the capacitive, inductive or probe type. To detect the spatial position of a carriage movable in a coordinate axis along a guide, that is, to detect a primarily one-dimensional movement, the known device is less suited because it is too complex for this purpose.
GB 2 034 880 A discloses an apparatus equally designed in particular to perform linear measurements in two dimensions. In addition, it provides a carriage movable along guide rails in two dimensions over a base. The carriage includes a surface upon which may be placed an object to be measured. The underside of the surface carries a first optical grating comprising parallel lines extending at right angles to one another. A probe is positioned above the surface. Secured to the base under the carriage are two reading heads for detecting movements of the carriage in two vertical directions. Due to its structural design this known apparatus is not suited either for the detection of the spatial position of a carriage movable in a coordinate axis along a guide of a machine tool or a measuring apparatus.
DE 43 08 456 C2 discloses a device which, for determining the position of a body to be positioned with respect to a prismatic reference body, detects the six degrees of freedom of the body to be positioned with respect to the reference body. The reference body carries on one of two surfaces disposed at right angles to one another two graduated scales, and on the other surface one graduated scale. The three graduated scales are designed as optical samplers in the form of CCD lines. The body to be positioned carries three projectors associated with the three graduated scales. Each projector emits three diverging light planes intersecting in a projection center, each light plane projecting three light marks onto the graduated scales. From the position of the individual light marks on the graduated scales it is possible to compute the spatial position of the projection centers longitudinally of the reference body and their distance to the corresponding surfaces of the reference body. These measurement values determine the position of the body to be positioned in its six degrees of freedom relative to the reference body.
It is an object of the present invention to improve a device of the type initially referred to so that defects of geometry in a linear axis of machine tools or measuring apparatus are without effect, which is accomplished by performing a continuous detection of a spatial position of the corresponding carriage directly, said device being desirably integrable into a machine or measuring apparatus construction.

Apparatus for detecting the position in space of a carriage moveable along a coordinate axis


A system controls the feed rate of parts delivered by a parts feeder having a vibrating unit to be vibrated with a predetermined amplitude for delivering parts and a driving unit for driving the vibrating unit. The control system has a parts detector for detecting parts delivered by the vibrating unit. A power transistor bridge supplies an alternating driving electric current to the driving unit. A driving voltage controlling circuit applies a predetermined direct current voltage to the power transistor bridge. A power transistor base driving circuit causes the power transistor bridge to function at a predetermined driving frequency. A central processing unit measures the supply rate of parts based on a signal transmitted by the parts detector and transmits a signal for regulating the driving voltage to the driving voltage controlling circuit and a signal for regulating the driving frequency to the power transistor base driving circuit in response to the supply rate of parts.

1. Field of the Invention
This invention relates to a control system for a parts feeder, and more particularly to a system for controlling the feed rate of parts delivered by the parts feeder which feeds various kinds of parts to an assembling machine or the like by vibrating tile parts at a predetermined frequency.
2. Description of the Prior Art
Heretofore, various kinds of vibrating type parts feeders are known in the art. For example, published Japanese Utility Model Application, KOKAI (Early Publication) No. SHO 59-68715 discloses a parts feeder which comprises a bowl provided with a side wall having a spiral passage formed on the inner peripheral surface thereof in the form of a gently upwardly sloping surface and an electromagnet disposed beneath the bowl, the bowl being adapted to accommodate a large number of parts, the arrangement being made such that then the bowl is vibrated by the action of the electromagnet, the parts within the bowl are transferred along the passage and delivered in turn while they are being vibrated by the vibration of the bowl.
As for the system for controlling the driving of such a parts feeder, for example, published Japanese Patent Application, KOKAI No. SHO 57-27808 proposes a system wherein a light projector and a receptor of a photoelectric conversion device are disposed on a straight line so as to pass light beams through the clearance between a fixed core of an electromagnet disposed beneath the bowl and a movable core fixedly secured to the bowl, the arrangement being made such that the change in the amount of light passing through the above-mentioned clearance due to changes in the amplitude of vibration of the movable core is converted into a value of electric current to detect the amplitude of vibration of the bowl, and the amplitude of vibration of the bowl thus obtained is fed back to an amplitude controlling circuit so as to control an electric current supplied to the electromagnet for driving the bowl, thereby driving the bowl always with a predetermined amplitude. Further, there has so far been used a parts feeder provided with a photoelectric switch attached to a parts delivery chute disposed on the side of outlet for tile parts so that the photoelectric switch may detect whether the parts delivered by a bowl are overstocked in the chute or not.
In the above-mentioned conventional control system, since the object to be controlled is the bowl for delivering the parts by vibrating them and the feed rate of the parts is not grasped and controlled, there is a problem in that changes in the feed rate of parts occurs depending on the amount of the parts accommodated in the bowl. That is to say, even if the vibration of the bowl is controlled to a prescribed amplitude, the feed rate of the parts changes because the proper value of the amplitude for ensuring a desired feed rate varies with the number of the parts accommodated in the bowl. In addition, since the actual feed rate of the parts is unknown, if the consumption of the parts by the assembling machine is out of balance to the supply of the parts by the parts feeder at the time of initial setting, shortage in supply of the parts to the assembling machine takes place even if the amplitude of vibration of the bowl is kept constant. Further, another problem is that since the proper value of amplitude differs with every parts feeder, in case the parts feeder is replaced with a new one, the vibration of the bowl must be reset to a proper amplitude to ensure a desired feed rate of the parts.


Devices connected with a computer system are interrogated to detect whether they are configured and functioning. In an audio device implementation, a known audio sample is output to a loudspeaker. If the loudspeaker is properly configured and functional, an attached microphone will capture the sound corresponding to the audio sample generated by the loudspeaker. If sound corresponding to the audio sample is detected, an indication is provided to the user that the microphone and loudspeaker are operational. If no sound corresponding to the audio sample is detected, an indication is provided to the user that the loudspeaker is not enabled and additional configuration is required.

Real-time communication using network-connected computing devices is becoming increasingly popular. This may take the form of, for example, voice over Internet protocol (VOIP) telephony, audio-enabled chat programs, and audio and video streaming. Providing the highest quality audio and/or video experience can be a differentiator among the many companies providing real-time communication audio clients. A real-time audio client typically requires a user to select and configure the audio devices to use for making a call. However, the user's selection does not guarantee that the audio devices are receiving or playing audio. Present configuration processes on audio clients only check a portion of the overall audio system. Thus, for example, the audio client can determine that it is sending a sound sample to a loudspeaker, but cannot determine whether the loudspeaker is actually playing the sound. Similarly, the audio client may test to determine whether the microphone is working by asking a user to speak into the microphone, but the audio client has no way of knowing whether the user actually responded if no signal is recorded within a certain period of time.
The information included in this Background section of the specification is included for technical reference purposes and is not to be regarded as subject matter by which the scope of the invention is to be bound.

This patent is subject to a terminal disclaimer.


A method is for preparing 1-(4-chlorophenyl)-2-cyclopropyl-1-propanone and an intermediate thereof, where in the method for preparing a compound of formula (I), α-alkoxy p-chlorobenzyl phosphonate (II) and cyclopropyl methyl ketone are used as raw materials, and subjected to a Homer-Wadsworth-Emmons reaction in an organic solvent in the presence of a base, so as to prepare a derivative of alkoxy propylene with the structure of formula (III); and the resulting derivative of alkoxy propylene (III) is hydrolyzed under acidic conditions to obtain 1-(4-chlorophenyl)-2-cyclopropyl-1-propanone (I).

1-(4-chlorophenyl)-2-cyclopropyl-1-propanone (I) is a key intermediate used in the production of the of fungicide cyproconazole.

The several known methods for preparation of the above compound are described in the prior literature, such as, U.S. Pat. No. 4,664,696, CN101786948A, RU2350579, CN101125807A, U.S. Pat. No. 4,973,767, and CN101857576 A. However, said methods require using dangerous and/or highly toxic chemicals, and, in some cases, would be difficult for industrialization because of hardly controlled reaction process, high production cost and the like.

Method for preparing 1-(4-chlorophenyl)-2-cyclopropyl-1-propanone and intermediate thereof

Jiangsu Chengyang Crop Science Co., Ltd.


A pneumatic tire includes a tread, two circumferentially extending annular bead regions, a carcass structure, and an overlay ply. The tread is rotatable about an axis and contacts a road surface. The tread further has an equatorial plane intersecting the axis at 90°. The carcass structure extends between the tread and the bead regions. The carcass structure supports the tread about the axis. The carcass structure includes two or more carcass plies having reinforcing cords oriented to cross at opposite angles of 20° to 65° with respect to the equatorial plane. The overlay ply extends circumferentially and extends radially between the carcass structure and the tread. The overlay ply includes cords oriented between −5° and +5° relative to the equatorial plane.

Conventional motorcycle tires utilize very wide treads which in transverse cross-section are sharply curved to provide good contact with the road surface when the motorcycle is steeply banked in cornering. Maintaining a consistent ground contact area or 'tire footprint' under all conditions is a major challenge in determining general vehicle handling.
Conventional radial motorcycle race tires have short sidewalls which extend to the tread edges radially and axially outwardly from the tires beads. The beads provide engagement to the wheelrim on tapered bead seats. The sidewalls are reinforced by radial carcass plies which, when tensioned by inflation pressure, act together with sidewall geometry to locate the curved tread regions to withstand cornering forces.
The sharply curved tread region of a motorcycle tire may be reinforced by a breaker to give the required structural rigidity and to allow for banking over of the motorcycle when cornering while still allowing sufficient flexibility for localized tread flattening in the ground contact patch for road grip. A conventional tread may further have three separate compound zones, each of which has full tread thickness.
It therefore an object of the present invention is to improve the properties of such motorcycle tires.

Motorcycle tire having a hybrid construction


Recognition of the role of a cellular immune response to immune-privileged antigens in the etiology of paraneoplastic syndromes and tumor immunity has provided diagnostic and therapeutic methods for the detection of paraneoplastic antigen-specific cells, enhancing tumor immunity by increasing the population of cytotoxic T lymphocytes (CTLs), and suppressing cellular immunity to treat the paraneoplastic syndrome. Methods for the detection of memory and cytotoxic T lymphocytes are provided which utilize immune-privileged antigens or their peptides. Enhanced CTL production is provided by stimulating antigen presenting cells in vitro with immune-privileged antigen, with and without further exposure to T lymphocytes, prior to reintroduction of either the antigen-presenting cells and/or the T lymphocytes into the patient. Suppression of the cellular response to non-tumor cells expressing the immune-privileged antigen is provided by using agents which suppress; anti-cytokine therapy is also provided to limit cell surface expression of paraneoplastic antigens by non-tumor cells. Compositions comprising immune-privileged antigen peptides useful for diagnostic methods and therapeutic treatments are also described.

This invention relates to diagnostic and therapeutic methods based upon the development of cellular immunity to immune privileged antigens and its role in the etiology of paraneoplastic neuronal disorders and tumor immunity, among other conditions.
Constant surveillance of epitopes throughout those structures in the body accessible to the immune system provides a very effective means for recognizing and maintaining xe2x80x9cselfxe2x80x9d and destroying epitopes and their carriers which invade the body or arise pathologically, such as infectious microorganisms. One important role of immune surveillance is the recognition and destruction of neoplastic cells that are believed to arise continuously in the body and for the most part are eliminated by the immune system before becoming detectable. However, examples of naturally-occurring tumor immunity have been elusive. Cytotoxic T lymphocytes, key participants in effective immune surveillance, are not expanded in patients with active tumors, even when these tumors express what are believed to be tumor-specific antigens such as the MAGE/MART antigens of melanoma.
Effective tumor immunity has been documented, however, in individuals with paraneoplastic neuronal disorders (PNDs). These syndromes are poorly understood diseases in which serious effects of cancer in the body occur in the nervous system without any direct involvement of the tumor. PND patients typically present to physicians with neurologic dysfunction unaware that they harbor a tumor. For example, patients with ovarian or breast cancer who develop paraneoplastic cerebellar degeneration (PCD) have an effective tumor immune response (3,4,5; reviewed in 1,2,6), and moreover, the tumor expresses neuron-specific proteins (antigens). These patients have in circulation and in the cerebrospinal fluid (CSF) antibodies against these tumor cell antigens, which also cross-react with the same proteins expressed in neurons, termed onconeural antigens. A high titer antibody recognizes the intracellular antigen cdr2 expressed in the ovarian or breast tumor present in PCD patients (10); and also recognizes the antigen in Purkinje neurons of the cerebellum (10). However, as will be elaborated below, the existence of this antibody does not account for the etiology of the PND nor for effective tumor killing.
Certain regions of the body, such as the brain, eye, and testis, are protected from immune surveillance, these sites are referred to as immune privileged. Based on the above observations, the immune system is proposed to initiate PCD by recognizing the normally immune-privileged antigen cdr2 (10) when it is ectopically expressed in gynecologic tumors. This immune response is associated clinically with effective tumor immunity, and is believed to lead to the recognition and destruction of Purkinje neurons expressing cdr2. cDNAs encoding several of the target antigens have been cloned, for example, cdr2 which has been shown to be the correct tumor antigen (9,54). However, because the target neuronal antigen is cytoplasmic, the role of circulating and cerebrospinal fluid (CSF) antibodies against these antigens in the pathogenesis of PCD is questionable. Moreover, attempts to reproduce the disorder by passive or active transfer of antibodies have failed (11,12,13). As the target organ, the brain, is immune privileged, and furthermore the target antigen is cytoplasmic, the etiology of the paraneoplastic syndrome is difficult to reconcile. This is further confounded by the apparent absence of a cellular immune response against tumor antigens in general and the apparent absence of a cellular immune response in PCD. No cytotoxic T lymphocytes were found against the cdr2 protein using autologous dendritic cells in a patient with PCD (47). The etiology of tumor immunity in PND is enigmatic.
As described above, the paraneoplastic syndromes are serious conditions associated with tumors and frequently affect the central nervous system; these disorders are collectively referred to as paraneoplastic neuronal disorders (PND). For example, one common paraneoplastic disorder which is seen in patients with breast or ovarian cancer is paraneoplastic cerebellar degeneration, or PCD, in which a progressive and severe neurological dysfunction occurs involving the cerebellum, leading to dyscoordination of the legs and arms, dizziness and double vision. Frequently, these symptoms appear before the diagnosis of cancer. In another example of neurological degeneration, Hu syndrome is associated with small cell lung cancer and antibodies to the onconeural antigen Hu. In other examples, opsoclonus, or spontaneous, chaotic eye movements, and myoclonus, jerky body movements, may accompany breast cancer, fallopian tube cancer, or small cell lung cancer, and are associated with antibodies to the onconeural antigen Nova.
The target onconeural antigens have yet to be identified for some disorders believed to be paraneoplastic. Patients with Hodgkin""s disease and other lymphomas may develop subacute cerebellar degeneration that is believed to be immune mediated (22,42). Eaton-Lambert syndrome, a condition causing weakness in the limbs, may also accompany intrathoracic tumors such as lung cancer and is believed to be immune mediated (2). Some patients who develop spinal cord dysfunction (e.g., myelopathy), motor neuron diseases, blindness and other neurologic symptoms are found to have specific sets of underlying tumors and are believed to have immunity to unknown or partially-characterized onconeural antigens (2,37). Less well understood, the incidence of the muscle diseases dermatomyositis and polymyositis is increased in cancer patients. The dermatologic condition vitiligo, in which melanocytes producing skin pigment are destroyed, appears associated with a decrease in incidence of melanoma. It is thus apparent that an association exists between tumors, and in some cases tumor immunity, and the sites of the paraneoplastic disorder symptoms, perhaps through the existence of some common antigens.
Several lines of evidence suggest the existence of naturally-occurring tumor immunity in PND patients. PND-associated tumors are typically occult (24,25); in several cases they have been identified only by microscopic analysis of suspect organs following exploratory surgery or at autopsy. Patients with PND-associated tumors have significantly-limited disease and an improved tumor prognosis relative to patients with histologically-identical tumors unassociated with PND (20,24,26-28). In some cases PND-associated tumors have been documented to regress with the onset of autoimmune neurologic disease (7).
Specific clinical data regarding anti-tumor immunity is available for several of the PNDs. Patients with paraneoplastic encephalomyelitis harbor high titers of an antibody termed Hu and small cell lung cancers (SCLCa); their tumors are typically limited to single nodules (53/55 [96%] patients in the most complete study published [3]). This is a remarkable finding given that most SCLCa patients from unselected series (over 60%) have widely metastatic disease at the time of diagnosis (and no detectable titers of Hu antibody). In addition, fifteen percent of SCLCa patients without PND nonetheless have detectable titers of the Hu antibody (20). These patients have statistically significant increases in the frequency of limited stage disease, complete response to chemotherapy and longer survival (3,5). These results suggest that anti-PND antibodies may be associated with suppression of tumor growth independently from their association with neurologic disease.
There are also firm associations between the presence of the Nova (Ri) (28) and Yo (10) antibodies in PND patients and clinically-limited malignancy. Both antibodies are found in women with gynecologic cancer. Of 52 Yo-antibody-positive patients with breast or ovarian cancer (4), two-thirds (34/52) presented with neurologic symptoms prior to the diagnosis of cancer, and 87% (45/52) had limited oncologic disease when diagnosed; similarly, 4/7 Nova-positive patients presented with neurologic symptoms, 6/7 had limited stage disease, and no tumor could be found in one patient (28). By comparison, only 50-60% of unselected breast cancer patients, and 25% of ovarian cancer present with limited stage disease (8).
Experimental observations support the clinical evidence that there is immunologic recognition of tumor cells in PND. High titer anti-PND antibodies are found in the serum and cerebrospinal fluid of PND patients. In vitro, these antibodies react specifically with tumor specimens obtained from PND patients cells, as well as neurons from clinically affected areas of the nervous system (24,25, 29). For example, 10/10 breast or ovarian tumors from Yo-positive patients were immunoreactive with biotinylated Yo antisera (4), and 3/4 breast or fallopian tumors from Nova-positive patients were immunoreactive with biotinylated Nova antisera (28). Taken together, these observations suggest that PND antibodies are more than markers for neurologic disease or even the presence of tumor cells, but are markers, and perhaps in part reflective of effective anti-tumor immune responses.
The immunologic basis of the anti-tumor and antineuronal immune response in PND is unknown. The finding of autoantibodies with neuronal binding specificity, and observations on autoimmune neurologic disorders of the peripheral nervous system, have focused attention on the role of B cells in the pathogenesis of PND. In myasthenia gravis (MG) and Lambert-Eaton myasthenic syndrome (LEMS), antineuronal antibodies have been found to passively transfer autoimmune disease in animals (30, 31). In PND, there are relatively higher titers of antibody in the CSF than serum (IgG index greater than 1) (32) suggestive of an active B cell inflammatory response within the CNS compartment. Furthermore, although the data is not fully compelling, there have been numerous reports that PND antibodies may be neurotoxic in vitro and that antibodies may be able to be taken up by neurons (33,34). These observations have led clinicians to focus therapy for the PNDs on the elimination of PND antibodies. Unfortunately these attempts have been uniformly unsuccessful (24, 32, 35). Several features of the PNDs distinguish them from MG and LEMS and suggest that B cells might not be sufficient or even necessary for the development of PND. PND antigens have been found to be cytoplasmic (Yo, xcex2-NAP) or nuclear (Nova, Hu) proteins, unlike the target antigens in MG (the acetylcholine receptor) or LEMS (the presynaptic calcium channel) (2). It is difficult to reconcile these observations with the premise that PND antibodies play a primary role in PND autoimmunity. Moreover, attempts to produce animal models of PND, including infusion of antibody into the CSF and immunization with cloned fusion protein, have failed (11, 12).
Thus, the etiology of the paraneoplastic syndromes appears to have an immunological basis, heretofore undefined. It is towards a better understanding of the etiology of the paraneoplastic neuronal disorders and the establishment of a link between effective tumor immunity and these serious, remote complications of neoplasia in immune privileged sites that the present invention is directed, with objectives of improving the detection of tumors and paraneoplastic disorders in individuals in general and offering improved therapies for both tumors expressing immune privileged antigens and the associated syndromes.
The inventors herein have made the surprising and remarkable finding of the presence of tumor antigen-specific T lymphocytes (CTLs) in patients with paraneoplastic neuronal disorders. This finding provides a basis for understanding the desirable and often effective cell-based immunologic attack on the tumors, and the effective but undesirable attack on remote target organ(s) of the paraneoplastic disorders by CTLs. Expression of the same immune-privileged antigen by these remote tissues as that which is expressed in the tumor cells, and to which T lymphocytes are targeted, explains for the first time the etiology of the PNDs. Both activated CTLs and memory T lymphocytes specific for the tumor and for the remote antigen have been detected. This finding provides an appreciation that immune privileged antigens offer a unique set of targets for the immune system. If expressed in tumors, they provide targets for effective anti-tumor immunity. If immune-privilege or tolerance to these antigens is broken, for example in the setting of effective anti-tumor immunity, autoimmune disease may result. The identification of a cellular immune response to immune-privileged antigens that can be readily and specifically detected, amplified, or inhibited, provides the basis for diagnostic and therapeutic utilities disclosed herein. Based upon this discovery, diagnostic utilities are disclosed for the detection and monitoring of cellular immunity to privileged antigens, and therapeutic methods are described for increasing the effectiveness of anti-tumor immunity and also for protecting the immune privileged site from immune-mediated pathology. Known diagnostic and therapeutic procedures and manipulations of the immune system are modified based on the discoveries herein in order to detect and modulate the immune response to immune-privileged antigens.
As will be described in more detail, below, only a fraction of patients with a specific T lymphocyte response to immune privileged antigens, especially those with tumors, exhibit an overt paraneoplastic disorder, yet such patients are at risk for the development of, or may have as-yet undetected autoimmune disease or another subclinical disorders. In accordance with the present invention, methods for determining in an individual the presence and extent of a cellular immune response to an immune-privileged antigen are provided, the cellular immune response associated directly or indirectly with a pathological state. Examples of pathological states include but are not limited to dysproliferative diseases, paraneoplastic syndromes, and autoimmune disorders. The method comprises quantitating in a sample of bodily fluid from an individual the presence and extent of T lymphocytes specific for the immune-privileged antigen or its fragments. The preferred method involves the detection of T lymphocytes which recognize paraneoplastic antigens, and most preferably, onconeural antigens such as cdr2 and Hu antigen. One example of a means for detection comprises determining the extent of activation of T lymphocytes upon exposure to the antigen by measuring cytokine production; another method comprises detecting the extent of recognition by the cytotoxic T cells of target cells expressing the antigen. Methods for detecting T lymphocytes bearing receptors for immune-privileged antigen are also provided.
In the instance where the T lymphocytes to be detected are memory T cells, the methods comprises detecting the extent of activation of memory T cells after exposure to antigen-presenting cells (APCs) presenting the immune-privileged antigen. In another embodiment, the extent of recognition of target cells expressing the antigen is determined after exposure of the memory T lymphocytes to APCs presenting the immune-privileged antigen.
The present invention further provides a method for screening individuals for the presence of tumors expressing immune-privileged antigens as well as detecting the early onset or propensity to develop a pathological state caused by a cellular immune response to an immune-privileged antigen. This method comprises measuring the presence and extent of T lymphocytes specific for immune privileged antigens. Furthermore, a method is provided for determining whether a neoplasm expresses an immune-privileged antigen by quantitating T lymphocytes that are specific for the antigen or its fragment. In another embodiment, a method is disclosed for determining whether a patient with a immune-privileged antigen-expressing tumor has a sufficient population of antigen-specific T lymphocytes to control the tumor or is a candidate for anti-cancer therapy. This method comprises quantitating T lymphocytes specific for the antigen or a fragment. In a still further embodiment, a method for monitoring the effectiveness of therapies directed to modulate the population of immune-privileged antigen-specific T lymphocytes in a patient is described wherein the numbers of antigen-specific T lymphocytes are quantitated.
The cDNAs encoding the target immune-privileged as well as their expressed proteins and fragments thereof may be used in the present invention to provide reagents for carrying out the diagnostic and therapeutic methods as described herein, as well as being part of a diagnostic kit. As described above, the sequence and cDNA of cdr2 is known (9,54); its fragments that complexes with HLA are described below.
In a further example of a screening method for identifying the number of immune-privileged antigen-specific T cells in a patient sample, the following steps may be carried out:
i) maturing dendritic cells in the blood sample;
ii) exposing the matured dendritic cells to apoptotic debris from unrelated cells expressing an immune-privileged antigen;
iii) co-incubating the immune-privileged antigen-exposed dendritic cells with the peripheral blood lymphocytes from the patient; and
iv) correlating the amount of interferon-xcex3 released from the lymphocytes with the number of immune privileged antigen-specific T cells in the sample.
By way of non-limiting example, the immune-privileged antigen may be cdr2. The unrelated cells expressing an immune-privileged antigen may be cells stably transfected to express an immune-privileged antigen, such as cdr2. The interferon-xcex3 release may be measured in an ELISPOT assay.
Diagnostic kits are also provided with componentry capable of measuring the above-described T lymphocytes and antigens comprising, for example, one or more of the following reagents: an isolated, immune-privileged antigen or preferably a fragment of the immune-privileged antigen; a target cell expressing the immune-privileged antigen or its fragment; a fragment of the immune-privileged antigen in a tetrameric complex with HLA; and a reagent such as an antibody or labeled antibody which recognizes a fragment of the immune-privileged antigen in a complex with HLA. When the immune-privileged antigen is cdr2, useful isolated polypeptide sequences identified include cdr2 peptides referred to as Yo1 through Yo8, or cdr2-1 through cdr2-8, and identified herein as SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7 and SEQ ID NO:8. The kit may include target cells prepared from a cell line or, for example, Drosophila, which expressed the immune-privileged antigen, and further may express HLA molecules and co-stimulatory molecules. A kit may further include components for detecting cytokine production, such as xcex3-IFN, as a means for detecting immune cell activation. To broadly screen samples from a variety of patients with different HLA haplotypes, a variety of target cells expressing the same immune-privileged antigen, but different HLA haplotypes, may be employed in order to detect immune-privileged antigen specific T lymphocytes regardless of the patient""s HLA haplotype.
It is another object of the present invention to provide methods for treating a neoplasm in a patient in which the neoplasm expresses an immune-privileged antigen. One preferred embodiment is accomplished by increasing the number of immune-privileged, antigen-specific cytotoxic T lymphocytes present in the patient. In one, non-limiting example, the method is carried out by first isolating a quantity of APCs from a sample of the patient""s blood, then exposing the APCs in vitro to the immune-privileged antigen or its fragment, followed by reintroducing the antigen-exposed APCs to the patient. In another related embodiment, the same method is followed with an additional step of exposing the antigen-exposed APCs in vitro to a quantity of T lymphocytes isolated from the patient, and reintroducing the T lymphocytes to the patient. These examples are illustrative of methods of providing the patient with immune privileged antigen-specific T lymphocytes and/or immune-privileged antigen-presenting APCs in order to develop or enhance immunity to the tumor.
Methods for achieving presentation of the immune-privileged antigen or its fragment on the APCs in the aforementioned methods is achieved using any one of several methods. For example, APCs are provided with apoptotic cells expressing the immune-privileged antigen or a fragment. These can be commonly available cell lines expressing the immune privileged antigen, such as HeLa cells, which express the cdr2 antigen (9), or transfected cells such as Drosophila cells expressing the gene encoding the immune-privileged antigen. These cells may also be further engineered to additionally express the gene encoding the MHC molecule haplotype of the patient, and even further engineered to express co-stimulatory molecules, such that the Drosophila cells function as an antigen-presenting cell, thus forming a useful APC for in-vivo or ex-vivo stimulation of T lymphocytes as described above. These cells also have diagnostic utility, as described herein. The preferred antigen is a paraneoplastic antigen, and most preferred, an onconeural antigen such as cdr2 and Hu antigen. In a further embodiment, the immune-privileged antigen-specific T lymphocytes are derived from a donor individual of the same HLA haplotype as the patient.
In a further embodiment of the present invention, a method for treating a pathological state in a mammal is provided, wherein the pathological state is caused by the presence in the mammal of T lymphocytes specific for an immune-privileged antigen. The method consists of administration of an effective amount of an agent which decreases the population of activated T lymphocytes specific for cells expressing the immune-privileged antigen. Non-limiting examples of such agents include tacrolimus, cyclosporin, immunosuppressive cytokines, corticosteroids, and combinations. The preferred agent is tacrolimus. The immune-privileged antigen is preferably a paraneoplastic antigen, most preferably, and onconeural antigen such as cdr2 and Hu antigen and their fragments. The preferred route of administration of the agents is to the central nervous system. Other effective routes of administration are also disclosed.
In a further embodiment of the present invention, a method is provided for decreasing the ability of non-tumor cells expressing privileged antigens to be killed by cytotoxic T lymphocytes as well as decreasing the expression of paraneoplastic antigens on non-tumor cells. These may be achieved by several methods, for example, by reducing the cytokine level in contact with the affected cells; increasing the expression of Nef or Nef-like proteins, inhibiting perforin-mediated CTL killing of neurons, and inhibiting apoptosis of the target cells.
In another embodiment, methods and agents are provided for enhancing the killing of tumors expressing immune privileged antigens by T lymphocytes. These methods include administering cytokines, inhibiting Fas-ligand expression in the tumor, and inducing the expression of MHC I molecules on the tumor. Other methods may be used in combination with increasing the immune-privileged T lymphocyte activity in the patient.
In a preferred embodiment, an individual with a tumor expressing an immune-privileged antigen and also suffering from a paraneoplastic disease or other syndrome in which the immune system is recognizing and attacking the same antigen at a non-tumor site within the body is treated by increasing the immune recognition of the immune-privileged antigen of the tumor exemplified by the non-limiting examples of methods disclosed herein, while concurrently protecting the non-tumor site from immune attack by the corresponding methods disclosed herein.
It is thus a principal object of the present invention to take advantage of the presence of immune-privileged antigen-specific T lymphocytes to detect the existence of a pathological state in a patient and to monitor the efficacy of treatments based upon the enhancement of tumor immunity by T lymphocytes as well as their suppression in the treatment of the associated syndrome in the non-tumor site. It is a further object of the present invention to provide both diagnostic and therapeutic purposes for the detection of tumors and paraneoplastic syndromes, to increase the immune destruction of such tumors as well as to protect the non-tumor organs susceptible to disease caused by the same T lymphocytes.
These and other aspects of the present invention will be better appreciated by reference to the following drawings and Detailed Description.

Methods and agents for the detection and modulation of cellular immunity to immune privileged antigens


The present invention provides an electrolyte solution and a lithium ion secondary battery which maintain for a long period high battery characteristics represented by the discharge capacity retention rate after the charge/discharge cycle, and simultaneously achieve also the high safety represented by the flame retardation. The present invention provides an electrolyte solution containing a nonaqueous solvent, an electrolyte, a specific compound having a perfluoroalkyl group in the molecule, and an additive having a fluorine atom and/or a phosphorus atom in the molecule.

Along with recent year's expansion of electronic technologies and growing concern in environmental technologies, various types of electrochemical devices have been used. Particularly, there are many demands for energy saving, and expectations for things capable of contributing to the demands increasingly become high. The things include, for example, solar batteries as power generation devices, and secondary batteries and capacitors as power storage devices. Lithium ion secondary batteries as a representative example of power storage devices have been originally used mainly as rechargeable batteries for portable devices, but in recent years, they have been expected to be used as batteries for hybrid cars and electric cars.
Now then, these electrochemical devices are used over a long period of several years to several tens of years, and demanded to exhibit a high efficiency and a low cost, and additionally, an elongated life (high durability) and high safety as well. However, since materials constituting these electrochemical devices include also materials easily combustible and materials easily deteriorating, there remains a problem in achievement of elongated life and high safety.
Lithium ion secondary batteries representative as power storage devices usually have a constitution in which a positive electrode and a negative electrode constituted mainly of active substances capable of doping and dedoping lithium are disposed across a separator. In the lithium ion secondary batteries, the positive electrode is formed by coating a positive electrode mixture obtained by mixing LiCoO2, LiNiO2, LiMn2O4 and the like as positive electrode active substances, carbon black, graphite and the like as conductive agents, and polyvinylidene fluoride, a latex, rubber and the like as binders, on a positive electrode current collector composed of aluminum or the like. The negative electrode is formed by coating a negative electrode mixture obtained by mixing coke, graphite and the like as negative electrode active substances, and polyvinylidene fluoride, a latex, rubber and the like as binders, on a negative electrode current collector composed of copper or the like. The separator is formed of a porous polyolefin or the like, and has a thickness as very thin as several micrometers to several hundred micrometers. The positive electrode, the negative electrode and the separator are immersed in an electrolyte solution in the battery. Examples of the electrolyte solution include electrolyte solutions in which a lithium salt such as LiPF6 and LiBF4 is dissolved in an aprotic solvent such as propylene carbonate and ethylene carbonate, or a polymer such as polyethylene oxide.
Lithium ion secondary batteries are presently used mainly as rechargeable batteries of portable devices (see, for example, Patent Literature 1). However, an organic solvent-based electrolyte solution is used in the lithium ion secondary batteries, so there arises a large problem of further improvement of the safety. For the improvement of the safety, batteries have been developed including batteries using an ionic liquid (see, for example, Patent Literatures 2 and 3) as an electrolyte solution, a polymer battery and a gel battery (see, for example, Patent Literatures 4 and 5), a battery in which an additive for improving safety is added to an electrolyte solution (Patent Literature 6), and a battery using a fluorosolvent as an electrolyte solution (see, for example, Non Patent Literature 1).

Electrolyte solution and lithium ion secondary battery using the same


A pneumatic thermostat calibration device with a removable cover to protect the sensor needle from clogging and/or damage and the user from needle induced injury. The pneumatic thermostat calibration device should also be sized to fit in the pocket of a user. The pneumatic thermostat calibration device should also include a thermostat adjustment tool. It is emphasized that this abstract is provided to comply with the rules requiring an abstract, which will allow a searcher or other reader to quickly ascertain the subject matter of the technical disclosure. It is submitted with the understanding that it will not be used to interpret or limit the scope or meaning of the claims.

The environment of commercial, high-rise and low-rise buildings are often controlled by a variable air volume (VAV) box which regulates the air flow within the building. The VAV system includes a controller with an actuator which opens and closes a damper allowing air to flow into the building. The controller modulates the position of the damper by sending a signal to the actuator. The actuator causes the damper to open and close thereby controlling the amount of air flow. The controller receives a signal based on the ambient temperature measured at the thermostat. The ambient temperature is compared to the pre-set, desired temperature and a signal is generated based on the difference between the desired temperature and the actual, measured temperature. The controller responds to the generated signal. The actuator opens or closes the damper in response to the generated signal.
For example, if the ambient air temperature is less than the desired, pre-set temperature, the actuator will open the damper (in one of the system types) thereby allowing the heated or cooled air will flow into the building. There are a number of different types of VAV systems, some of which have the damper normally closed, or normally open. Some VAV systems use hot water reheat to control the VAV. In all of the systems it is important that the ambient temperature be accurately calibrated.
Pneumatic devices are typically used to measure the thermostat pressure. The "spring range" of the actuator is the amount of pressure required to modulate the opening of the actuation. For example, in a normally closed (damper) system, if the ambient temperature is 70 degrees Fahrenheit, the thermostat pressure is 7 psi and the spring ranges are 8–15 psi, i.e. 8–15 psi is required to open the actutator. In a normally open system, the spring ranges are 0–6 psi.
The pneumatic thermostat calibration devices may include a hollow needle attached to a pneumatic sensor. The sensor detects the pneumatic pressure when its needle is inserted into a pneumatic thermostat receiver.
When the control or desired pressure, and the corresponding temperature, of the pneumatic thermostat requires adjustment, a tool is employed to make the adjustment. One of the major drawbacks to the present thermostat calibration devices is that they typically do not include the thermostat adjustment tool with the pressure measuring device and a separate tool must be employed. Further, the different VAV systems which require different types of tools to adjust the different thermostats.
One of the problems encountered with currently-used thermostat calibration devices, is the needle is often vulnerable to clogging and/or damage. Lint, dust and/or other material may clog the sensor rendering it inoperable. The sharp needle may also pose a safety hazard to the user. The unprotected needle may prick or scratch the user when not in use. The unprotected needle is also subject to breakage.
A pneumatic thermostat calibration device with a removable cover to protect the sensor needle from clogging and/or damage and the user from needle induced injury is needed. The pneumatic thermostat calibration device should also be sized to fit in the pocket of a user. There has been a long-standing need for a pneumatic thermostat calibration device which includes a universal thermostat adjustment tool.


Notes may be shared in an online meeting with online meeting attendees through a software application associated with organizing an online meeting, for example, online meeting software, calendaring software, note-taking software, or the like. Notes may be created and/or shared before, during, and/or after the online meeting by meeting attendees. Meeting attendees may be notified when notes are shared for the online meeting. Notes may be shared with items of the software application associated with organizing the online meeting. For example, notes may be shared in online meeting software with the online meeting. Notes may be shared among items of different software applications, for example, notes shared in the online meeting software may be automatically shared with a calendar item in a calendaring software application.

Organizing meetings through a software application is a common experience for computer users. For example, a user may employ a meeting organizer software application to schedule a meeting, completing such tasks as inviting meeting attendees, reserving a conference room, and the like. In another example, a user may be a meeting presenter, and may employ an online meeting organizer software application to conduct an online meeting by online presentation of real-time audio and/or video of the meeting to meeting attendees.
The online meeting presenter may distribute notes before the meeting, e.g., via emailing the notes to meeting attendees or emailing a link to the notes in a location accessible to meeting attendees. Online meeting attendees may similarly provide their own contributions to the notes. However, this may rapidly become inconvenient when distributing notes via email, for example as the number of contributing meeting attendees increases. When the notes are stored in a location accessible to online meeting attendees, they may be accessed by an application providing multiple simultaneous authorship, permitting online meeting attendees to provide their own contributions to the notes. To date, however, such solutions leave the notes separated from the software for conducting or scheduling online meetings.


A TBET cassette including at least one xanthine- or pyronin-based compound as a donor or acceptor is disclosed. Also, a method of TBET cassette design in which four criteria may be used is provided. TBET cassettes may be used to label biological molecules, in clothing dyes, and in cosmetics.

When two fluorescent or molecular entities are joined together to form one molecule, they may, in some cases function as "energy transfer cassettes". Molecules that act as energy transfer cassettes are characterized by transfer of all or part of the energy absorbed by one of the otherwise fluorescent parts to the other, which then fluoresces with enhanced brightness. The molecular fragment that absorbs energy then donates it to the other part may be referred to as the donor, while the molecular fragment that collects energy from the donor and emits with enhanced fluorescence is typically called the acceptor.
There are various mechanisms by which a donor entity may transfer energy to an acceptor entity in the same molecule. Most frequently, the energy is transferred almost exclusively through space via a mechanism often referred to as Förster energy transfer. Energy transfer cassettes based on through-space energy transfer are extremely common.
Through-bond energy-transfer (hereafter, TBET) cassettes are rarer than through-space energy-transfer cassettes (TSET). Nevertheless, some examples have been described. The most notable ones include models for photosynthetic systems, various studies on polymeric or oligomeric systems for new materials, and other model studies featuring boron dipyrromethane dyes.

Fluorescent through-bond energy transfer cassettes based on xanthine and pyronin derivatives


A control method of an air conditioner system for an electric vehicle may include circulating the refrigerant by sensing actuation of the air conditioner system while driving the electric vehicle in a state where a start of the electric vehicle is turned on, circulating and cooling the cooling water through actuation of a water pump and a cooling fan in a cooling module that includes an engine radiator, the intercooler radiator, the water-cooled condenser, and the air-cooled condenser, and controlling actuation speeds of the water pump and the cooling fan based on whether the electric vehicle stops after suddenly accelerating in a state where the air conditioner system is actuated or stops in a state where the air conditioner system is turned off after travelling, and/or based on whether an air conditioner pressure and a cooling water temperature are within predetermined set values.

Field of Invention
The present invention relates to a control method of an air conditioner system for an electric vehicle, and more particularly, to an control method of an air conditioner system for an electric vehicle that prevents a refrigerant from leaking due to deterioration in a seal caused by an increase in temperature of a compressor by preventing the refrigerant of which the temperature is increased from being supplied to the compressor by controlling operations of a water pump and a cooling fan, when the electric vehicle stops after suddenly accelerating in a state where an air conditioner is actuated or when the electric vehicle stops in a state where the air conditioner is turned off after the electric vehicle travels.
Description of Related Art
In general, an air conditioning device applied to a vehicle includes an air conditioner system which is an air conditioning device for heating and cooling an interior of the vehicle.
The air conditioner system, which can maintain a fresh indoor environment by keeping an indoor temperature of a vehicle to an appropriate temperature regardless of a change in outdoor temperature, is configured to heat or cool an interior of the vehicle by heat-exchange by an evaporator during a process in which a refrigerant discharged by driving a compressor is circulated to the compressor again by passing through a condenser, a receiver drier, an expansion valve, and the evaporator.
That is, in the air conditioner system, a high-temperature and high-pressure gaseous refrigerant compressed by the compressor is condensed through the condenser and thereafter, evaporated by the evaporator through the receiver drier and the expansion valve to lower the indoor temperature and humidity in a summer cooling mode.
Herein, when a water-cooled condenser is applied to the air conditioner system for cooling in order to condense the refrigerant, cooling water is condensed through heat-exchange with the refrigerant in the condenser.
Meanwhile, in recent years, an intercooler has been applied to improve an output of the vehicle and is divided into an air-cooled intercooler or a water-cooled intercooler according to a method of cooling suctioned air.
In the air conditioner system of a vehicle applied with a system that cools the water-cooled condenser by using a radiator that cools the water-cooled intercooler through simultaneous application of the water-cooled intercooler and the water-cooled condenser as described above, when the vehicle stops traveling and stops while the air conditioner is turned on in a state where a heat emission amount maximally increases, after travelling due to sudden acceleration on an ascending road such as a mountainous region or when the vehicle stops in a state where the air conditioner is turned off after travelling, heat accumulated in the intercooler flows into the radiator, but driving-induced wind does not flow into the radiator which causes an increase in the temperature of the cooling water, and as a result, the refrigerant cannot be cooled by the cooling water in the water-cooled condenser and the refrigerant is additionally heated to make the refrigerant having the increased temperature flow into the compressor.
Further, when the high-temperature refrigerant flows into the compressor, the internal temperature of the compressor is increased and sealing applied to an inner part thereof is aged by heat, and as a result, the refrigerant may leak from the compressor and durability also deteriorates.
In addition, deterioration in condensing efficiency of the condenser and the durability of the compressor decreases overall cooling performance of the air conditioner system and increases required power of the compressor, and as a result, fuel efficiency also deteriorates.
The information disclosed in this Background section is only for enhancement of understanding of the general background of the invention and should not be taken as an acknowledgement or any form of suggestion that this information forms the prior art already known to a person skilled in the art.

Control method of air conditioner system for electric vehicle


A method of redeeming for a seller electronic payments generated by and received from a customer using a master key unknown to the seller. In anticipation of making electronic payments, a customer sends a bank the master key that he will use to generate electronic payments. The bank stores the master key. Later, the bank receives from the seller a redemption request including a seller identifier, a first value of a payment index, and an electronic payment associated with the first value of the payment index. The bank authenticates the electronic payment by comparing the electronic payment to a hash of a string including the master key, the seller identifier, and the first value of the payment index. If the electronic payment is authenticated, the bank determines an amount due to the seller and credits that amount to the seller.

Several trends motivate the need for small-sized financial transactions, often called microtransactions. First, the fine granularity of information on the World Wide Web (WWW) and competition with free information on the WWW gives rise to the need to pay very small amounts for information sold on the WWW. Second, the growing number of embedded processing elements in our everyday environment motivates the need for small payments as a technique for controlling our environment.
There is no well established definition of a microtransaction. Its principal characteristic is small size and overhead. As a result, microtransactions should be off-line from a central server, and easy to compute; however, most current electronic payment protocols are computationally intensive and/or require a great deal of memory space or state.
Accordingly, a need exits for a space efficient microtransaction protocol that is suited to the limited processing and memory capabilities of small portable computation platforms, like smart cards and personal digital assistants (PDAs).

Space efficient method of redeeming electronic payments


Provided is related to a flash memory device, comprising an input receiver to input data, a data selector for generating a plurality of control signals in accordance with recognizing whether the input data in the data receiver is either the data to be programmed or the data to be erased, a data load path being enabled for data to be programmed while disabled for data to be erased, in response to the control signal, and a page buffer for storing the input data from the data load path. The present invention improves a data loading speed and enhances power consumption property by reducing current dissipation.

1. Field of the Invention
The present invention relates to a flash memory device, and specifically, to a flash memory device improving loading speed and reducing current consumption, by selecting input data through IO pad and enabling a data load path for data to be programmed while disabling the data load path for data to be erased.
2. Discussion of Related Art
In applying data to NAND type flash memory cells, a data loading command is applied to the flash memory device and data are loaded on a page buffer 40 by way of IO pads with increasing address values in sequence. The data to be programmed, generally, are transmitted to the page buffer in the unit of byte or word in sequence. If data to be programmed, corresponding to a data volume of one page, are all loaded on the page buffer, the data stored in the page buffer are programmed in a memory cell array by a page program command all at once.
The page buffer conserves the potential of power supply voltage level Vcc as its initial value. That is, the initial value of the page buffer is set by a program bias condition. Typically, data input through IO pads are continuously written in the page buffer by way of data paths in a power supply voltage level Vcc or a ground voltage level Vss.
In a normal case of a NAND type flash memory device, the data should be loaded by 512×8 bit in 512 cycle times. But if the logical polarity of data is opposite to the previous data while loading the data, it increases current consumption, which causes power consumption heavier especially when 8-bit data is transferred at the same time.

Flash memory device capable of improving a data loading speed


An electrified vehicle electrical system includes, among other things, a contactor enclosure, and contactor contacts housed within the contactor enclosure. A resistor is housed within the contactor enclosure or is housed within a relay enclosure outside the contactor enclosure.

Generally, electrified vehicles differ from conventional motor vehicles because electrified vehicles are selectively driven using one or more battery-powered electric machines. Conventional motor vehicles, in contrast to electrified vehicles, are driven exclusively with an internal combustion engine. Electrified vehicles may use electric machines instead of, or in addition to, the internal combustion engine. Example electrified vehicles include hybrid electric vehicles (HEVs), plug-in hybrid electric vehicles (PHEVs), fuel cell vehicles, and battery electric vehicles (BEVs). Within a powertrain of an electrified vehicle, an electrical system can be used to control a flow of electric power to and from the high-voltage battery pack.

Integrated components of an electrified vehicle electrical system and electrical distribution method


The present invention provides novel glycosyltransferase proteins produced by ascomycetous filamentous fungi (preferably species belonging to the genus Trichoderma, more preferably Trichoderma viride), as well as genes encoding the same. Among novel enzyme proteins provided by the present invention, particularly preferred is an enzyme protein obtained from the culture supernatant of Trichoderma viride strain IAM5141. The novel enzymes of the present invention allow glycosylation of flavonoid compounds to thereby improve their water solubility.

Proanthocyanidin (grape seed extract) has been studied for its usefulness as a therapeutic agent for blood vessels, and one of the reasons for recent progress in these studies is that the target substance can serve as a marker for tracing in vivo absorption and metabolism because it is stable against heat and acids, highly soluble in water and highly absorbable in the body. In contrast, polyphenol compounds such as catechin are often difficult to dissolve in water, and also involve a problem in that they are less absorbable in the body.
Attempts have been made to develop a technique for glycosylation of catechin and other compounds, with the aim of improving their solubility in water and increasing their stability.
By way of example, Patent Document 1 discloses α-glucosidase with a molecular weight of about 57,000, which was collected from a culture solution of Xanthomonas campestris WU-9701. This enzyme uses maltose or the like as a donor (does not use maltotriose, cyclodextrin or starch as a donor) and transfers glucose to a specific acceptor to synthesize a glycoside. In this document, compounds listed as acceptors are those having an alcoholic hydroxyl group (e.g., menthol, ethanol, 1-propanol, 1-butanol, 2-butanol, isobutyl alcohol, 1-amyl alcohol, 2-amyl alcohol, 5-nonyl alcohol), as well as those having a phenolic hydroxyl group (e.g., capsaicin, dihydrocapsaicin, nonylic acid vanillylamide, catechin, epicatechin, vanillin, hydroquinone, catechol, resorcinol, 3,4-dimethoxyphenol). Moreover, glycosides whose production was actually confirmed are monoglucosides only.
Patent Document 2 discloses a method in which a mixture of a catechin compound and glucose-1-phosphate or sucrose is treated with sucrose phosphorylase to prepare a glycoside of the catechin compound. The sources of sucrose phosphorylase listed therein are Leuconostoc mesenteroides, Pseudomonas saccharophila, Pseudomonas putrefaciens, Clostridium pasteurianum, Acetobacter xylinum, and Pullularia pullulans. Likewise, catechin compounds listed as acceptors are (+)-catechin, (−)-epicatechin, (−)-epicatechin 3-O-gallate, (−)-epigallocatechin and (−)-epigallocatechin 3-O-gallate, but it is only (+)-catechin that was actually used as an acceptor to prepare (+)-catechin 3′-O-α-D-glucopyranoside in the Example section.
Patent Document 3 discloses epigallocatechin 3-O-gallate derivatives, in which a glucose residue or a maltooligosaccharide residue with a polymerization degree of 2 to 8 is attached to at least one of the 5-, 7-, 3′-, 4′-, 5′-, 3″-, 4″- and 5″-positions. As in the case of Patent Document 2, the Example section of Patent Document 3 actually discloses only a case where a mixture of (−)-epigallocatechin gallate and glucose-1-phosphate or sucrose was treated with sucrose phosphorylase to prepare 4′-O-α-D-glucopyranosyl(−)-epigallocatechin gallate and 4′,4″-O-α-D-di-glucopyranosyl(−)-epigallocatechin gallate.
Patent Document 4 discloses tea extracts or tea beverages whose astringent taste is reduced by glycosylation of polyphenols contained therein. To reduce the astringent taste of tea extracts or tea beverages, this document describes detailed procedures in which tea extracts or tea beverages are supplemented with dextrin, cyclodextrin, starch or a mixture thereof, and then treated with cyclomaltodextrin glucanotransferase. In the Example section, it is shown that a green tea extract and α-cyclodextrin were treated with cyclomaltodextrin glucanotransferase derived from Bacillus stearothermophilus to give a reaction product with reduced astringent taste, which in turn indicates that polyphenols such as epigallocatechin 3-O-gallate and epicatechin were glycosylated. However, this document fails to show the detailed structure of the reaction product.
Patent Document 5 discloses glycosides of catechin compounds in which glycosylation occurs at the 3′-position, at the 3′- and 5-positions, or at the 3′- and 7-positions. For this purpose, this document describes detailed procedures in which a catechin compound and dextrin, cyclodextrin, starch or a mixture thereof are treated with cyclomaltodextrin glucanotransferase derived from Bacillus stearothermophilus, as in the case of Patent Document 4. Further, in the examples using dextrin as a glycosyl donor in the above procedures, some of the resulting glycosides of (−)-epigallocatechin, (−)-epigallocatechin 3-O-gallate and (−)-epicatechin 3-O-gallate are considered to have 6 to 8 glucose residues on average per molecule of each polyphenol, as determined from their molar absorption coefficients. Moreover, it is confirmed that upon treatment with glucoamylase derived from Rhizopus niveus, the glycosides obtained by the above procedures generated 3′,7-di-O-α-D-glucopyranosyl(−)-epigallocatechin, 3′,5-di-O-α-D-glucopyranosyl(−)-epigallocatechin, 3′-O-α-D-glucopyranosyl(−)-epigallocatechin, 3′,7-di-O-α-D-glucopyranosyl(−)-epigallocatechin 3-O-gallate, 3′-O-α-D-glucopyranosyl(−)-epigallocatechin 3-O-gallate, 3′-O-α-D-glucopyranosyl(−)-gallocatechin and 3′-O-α-D-glucopyranosyl(−)-epicatechin 3-O-gallate.
As to effects provided by catechin glycosides, Non-patent Document 1 describes reduced astringent taste, increased water-solubility, improved stability and inhibited tyrosinase, while Non-patent Document 2 describes suppressed mutagenicity.                Patent Document 1: JP 2001-46096 A        Patent Document 2: JP 05-176786 A (Japanese Patent No. 3024848)        Patent Document 3: JP 07-10897 A (Japanese Patent No. 3071610)        Patent Document 5: JP 09-3089 A (Japanese Patent No. 3712285)        Non-patent Document 1: Biosci. Biotech. Biochem., 57 (10), 1666-1669 (1993)        Non-patent Document 2: Biosci. Biotech. Biochem., 57 (10), 1290-1293 (1993)

Polypeptide having glycosylation activity on a flavonoid


Ablation visualization and monitoring systems and methods are provided. In some embodiments, such methods comprise applying ablation energy to a tissue to form a lesion in the tissue, illuminating the tissue with a light to excite NADH in the tissue, wherein the tissue is illuminated in a radial direction, an axial direction, or both, monitoring a level of NADH fluorescence in the illuminated tissue to determine when the level of NADH fluorescence decreases from a base level in the beginning of the ablating to a predetermined lower level, and stopping ablation of the tissue when the level of NADH fluorescence reaches the predetermined lower level.

Atrial fibrillation (AF) is the most common sustained arrhythmia in the world, which currently affects millions of people. In the United States, AF is projected to affect 10 million people by the year 2050. AF is associated with increased mortality, morbidity, and an impaired quality of life, and is an independent risk factor for stroke. The substantial lifetime risk of developing AF underscores the public heath burden of the disease, which in the U.S. alone amounts to an annual treatment cost exceeding $7 billion.
Most episodes in patients with AF are known to be triggered by focal electrical activity originating from within muscle sleeves that extend into the Pulmonary Veins (PV). Atrial fibrillation may also be triggered by focal activity within the superior vena cava or other atrial structures, i.e. other cardiac tissue within the heart's conduction system. These focal triggers can also cause atrial tachycardia that is driven by reentrant electrical activity (or rotors), which may then fragment into a multitude of electrical wavelets that are characteristic of atrial fibrillation. Furthermore, prolonged AF can cause functional alterations in cardiac cell membranes and these changes further perpetuate atrial fibrillation.
Radiofrequency ablation (RFA), laser ablation and cryo ablation are the most common technologies of catheter-based mapping and ablation systems used by physicians to treat atrial fibrillation. Physicians use a catheter to direct energy to either destroy focal triggers or to form electrical isolation lines isolating the triggers from the heart's remaining conduction system. The latter technique is commonly used in what is called pulmonary vein isolation (PVI). However, the success rate of the AF ablation procedure has remained relatively stagnant with estimates of recurrence to be as high as 30% to 50% one-year post procedure. The most common reason for recurrence after catheter ablation is one or more gaps in the PVI lines. The gaps are usually the result of ineffective or incomplete lesions that may temporarily block electrical signals during the procedure but heal over time and facilitate the recurrence of atrial fibrillation.
PV isolation (PVI) can be accomplished in most patients using irrigated ablation catheters, however recurrence of AF may occur over time. Recurrences are thought to be due to PV reconnections from sites that either recovered, gaps in the ablation lines, or ablated sites that did not achieve transmurality during the initial procedure. Therefore, lesion assessment is very important in catheter ablation procedures so that the operator can deliver the best possible lesions during pulmonary vein isolation procedures. The improved quality of the lesions can reduce atrial fibrillation recurrences.
Real-time optical tissue characterization can provide excellent and previously impossible assessment of electrode-tissue contact and lesion progression during ablation. It can also provide highly valuable information regarding the myocardium, collagen, elastin tissue composition at the site of catheter tip and represents a new frontier in the understanding of the complex nature of the biophysics of cardiac ablation. Lesion depth directly correlates to a decrease in fNADH signal intensity. This information should be used to optimize the selection of ablation power and ablation energy application time to maximize lesion formation and improve the success of ablation procedures. Therefore, there is a need for systems and methods for real-time optical tissue characterization.

Systems and methods for lesion assessment


Method for improved in vivo production of taxanes by inoculation of tissue of the genus Taxus with virulent or avirulent strains of Agrobacterium. In the preferred embodiment, virulent Agrobacterium is the inoculant which induces gall formation at all stages of the plant, from saplings to mature trees. Incomplete harvesting of galls permits regeneration on the trees, resulting in a renewable resource. Unexpectedly, the inoculant tissue (both virulent and avirulent) produces approximately twice the concentration of taxanes per unit tissue weight as compared to normal tissue. In addition, the virulent strain induced gall biomass is 2-3 times greater than normal tissue per unit growth time, while avirulent inoculants show approximately the same growth as normal. The net yield increase is 2-6 times normal, (4-6 for galls), is renewable, does not require special growth hormones or media, does not result in sacrificing the tree, and can be started at the sapling stage. The post-growth phase production is uncoupled by the inoculation and concentration yield is doubled.

The group of complex terpene-type compounds known as taxanes have proven to have important anti-cancer properties. The reference herein to taxane, taxane-type compounds or taxol will be shorthand for this recognized group of compounds having anti-cancer activity and other properties.
The primary source of the anti-cancer drug taxol is bark tissue of Taxus brevifolia, the Western (Pacific) yew. The supply of this drug is limited by the number of these slow-growing trees available for harvest. Using current methods, trees are cut and bark is removed. The most bark is, of course, obtained from mature trees. Cutting, however, kills the tree and reharvesting awaits 20 years or more for regrowth. The rate of cutting threatens wild trees with extinction.
The yield of taxol/taxane compounds is measured in micrograms per pound of plant bark where the highest concentration of taxol is normally found. For example, to obtain 1 gram of taxol requires harvesting some 22 lbs. of bark which represents 2-3 mature trees of age 20-40 years. A typical cancer treatment involves from 1 to 2 grams per patient over the course of the treatment regime extending 3-6 months.
A variety of processes have been proposed for sources of taxol/taxanes and their derivatives, including: Callus cell culture techniques, managed tree farms, and classic organic synthesis.
For example, U.S. Pat. No. 5,019,504 of Christen et al. is directed to culturing selected tissue, preferably bark or cambial tissue, from Taxus brevifolia. Since cultured plant tissue ordinarily does not produce the same compounds in culture, culturing is not always successful and is tricky to maintain. That is, taxol production is non-growth associated, involving secondary metabolism. Culturing may interfere with the secondary metabolism products, although there is no uncoupling of the post-growth relationship as taxol/taxanes are not usually produced during the initial callus proliferation stage. Further, taxol production after suspension cell culture growth is best induced by fungal or inorganic elicitors in subcultures, the best results being shown in subcultures supported on special agar media.
In Science News, Feb. 22, 1992, page 124, it is reported that a variety of workers are attempting various organic syntheses, which are difficult. Growing vast numbers of trees on managed tree farms is another approach, but that takes time as taxol is produced in the older plants. It is climate limited, labor intensive, and requires an enormous investment in land and harvesting equipment.
Gasser and Fraley, in an article entitled Transgenic Crops, Scientific American, June 1992, p. 62 describes the formation of crown galls by the plant pathogen Agrobacterium tumefaciens. "This bacterium can transfer a portion of its DNA into plant cells. It does so by introducing a set of genes into one or more of its own [sic] DNA fragments. These fragments called transferred DNA (T-DNA), then integrate into chromosomes of infected plant cells and induce the cells to produce elevated levels of plant hormones. These hormones cause the plant to form novel structures, such as tumors or prolific root masses, that provide a suitable environment and nutrient source for the Agrobacterium strain. This bacterial infection is crown gall disease." The Sanford DNA particle gun used for plant genetic transformation is shown in this article.
Also, De Cleene, in a letter in Speculations in Science and Technology, Vol. 3, No. 3, August 1980, Elsevier Sequoia, Lausanne, pp. 353-356, proposed consideration of in vitro cell and tissue cultures of crown gall tissue as a source of physiologically active substances because of their possible greater metabolic activity. He cautioned that "It is true that the biosynthetic pathways are not necessarily the same for normal and crown gall tissues. Biochemical differences between both tissue types have been suggested in the literature, but crown gall tumors nevertheless seem to reflect the physiological state of the host plant from which it developed. So there is a good chance that therapeutically active compounds are synthersized in both healthy and crown gall tumors of a certain plant species." In inviting experimentation along this line of speculation, De Cleene listed some 22 species, one of which was "Taxus brevifolia Nutt. (Western yew): anti-tumor agent, cyanogenetic glycoside (taxiphyllen)."
Subsequent research dampened De Cleene's speculations. Thus, Norton et al. in Phytochemistry Vol. 24, No. 4 pp. 719-722 (1985) measured thiophene concentrations in crown gall tissue produced by Agrobacterium tumefaciens strains A208 and A277 of Tagetes patula plants (Marigold-French Dwarf Double, Sparky Mixed) and concluded that: "The results showed it is not possible to predict the amounts of secondary metabolites produced as a result of transfers of genetic material from infected plants to crown galls and then to transformed callus tissues." They also noted that: "Most of the publications to date (1985) contain results which show a reduced yield of secondary metabolite production by crown gall tissues or transformed callus tissues."
Huizing, H., Hibma, J. and Wichers, H., reported in Acta Botanica Neerlandica, 35(1):47 (1986) on their investigation of the feasibility of production of L-DOPA on crown-gall tumour tissue of Nucuna puriens (a dicot). Tumors were initiated on plants, removed and placed in culture to obtain hormone autotrophic cell lines. Transformed cells did not produce more L-DOPA than did cells which were grown in the presence of growth regulators.
Luckner, M., Moldenhauer, E., First, B., and Diettrich, B., in Plant Medica 56:498-499 (1990) reported on cardenolide accumulation in crown galls and cell lines obtained by transformation of Digitalis lanata (a dicot) with wild-type strains of Agrobacterium tumefaciens. Tumors were induced on sterile leaf disks obtained from greenhouse or in vitro plants and the tissue analyzed for digitoxin derivatives. The average content of products was only 30% that of the leaves the galls were attached to, but in some cases exceeded concentrations in the leaf. For digoxin, the results were different. Crown galls only contained about 1% that of the leaf.
Cosio, E., Norton, R., Towers, E., Finlayson, A., Rodriguez, E., and Towers, G. reported in J Plant Physiol 124:155-164 (1986) on production of antibiotic thiarubrines by a crown gall tumor line of Chaenactis douglasii (a dicot). They worked with a crown gall tumor line in vitro. They interpret their results as evidence of tissue organization in tumors being necessary for product formation. No data on freshly excised tumors was presented.
Accordingly, there is a need in the art to provide a process for increasing the rate of growth and concentrations in naturally growing Taxus tissue for increased yields of taxol/taxane-compounds.