A container made from corrugated paperboard has a bottom wall, opposite side and end walls, and a self locking arrangement on the end walls holding the container in erected condition. The self locking arrangement includes first and second end panels on opposite ends of the side walls, and a third end panel on opposite ends of the bottom wall. The end panels form the end walls of the container. The first and second end panels have at least one notch formed in an upper edge, and a roll over flap is foldably joined by at least one web to an upper edge of each of the third end panels and is folded inwardly and downwardly over the upper edges of the first and second end panels into a locked position to hold the end panels and thus the container in erected condition. In the locked position, the web is engaged in the notch. In particular, the web has a thickness less than the thickness of an end panel, so that it fits deeply into the notch, producing a tight fit and reliable interlocking of the components of the self locking arrangement.

1. Field of the Invention
This invention relates to packaging. More specifically, the invention relates to a multi-sided container or box made of corrugated paperboard. In particular, the invention relates to a corrugated paperboard tray for containing poultry products, wherein the tray is configured for manual set up and has an improved self locking feature for retaining the walls of the tray in erected position.
2. Prior Art
Various styles of containers, including paperboard boxes, are known in the prior art for containing a variety of products. Cut poultry pieces, for example, are frequently packed in a paperboard container, and sometimes the poultry pieces are packed with ice. These containers are generally referred to as poultry trays, and are usually made from a unitary blank of corrugated paperboard, which may be treated on one or both sides with wax or other material to impart rigidity and resistance to water degradation.
Conventional paperboard containers are configured for either machine set up or manual set up, and generally are either rectangular or octagonal in plan view, with four sides or eight sides, respectively. An example of a prior art eight sided container is disclosed in applicant's prior U.S. Pat. No. 5,752,648. The embodiment shown in FIGS. 1-3 of that patent is configured for manual set up, and has three overlapping end panels 18, 24 and 24, with notches 30 formed in the top edges of the two end panels 24, and a roll over flap 34 foldably joined to the top edge of end panel 18 by short narrow webs formed between transverse cuts or relief slits 37 extending in spaced relationship transversely across cut lines 36 and 38, and interrupting the cut lines. Pairs of short cuts or slits 39 are formed in the webs parallel to the cut lines 36 and 38, but spaced from one another on opposite sides of the cut lines a distance approximately equal to the combined thicknesses of the three overlapped end panels. The slits 39 promote bending or folding of the webs along fold lines extending through the slits.
To erect the container, the two end panels 24 are folded inwardly into overlapping registry with one another, and the end panel 18 is then folded into overlapping relationship with panels 24. The roll over flap 34 is then folded inwardly and downwardly over the upper edges of the panels 24, causing the webs to drop into notches 30, and the upwardly extending portions of panels 24 on opposite sides of the notches to project upwardly through the cuts formed by the cut lines 36 and 38. The relationship of the relief slits 37 and cut lines 36 and 38 causes a "heel" to be formed on the edge of the roll over flap, and this heel produces an over-center effect when the roll over flap is folded over the panels 24. The heel engages against the inner surface of the innermost end panel 24 to keep the roll over flap in its folded position, and thereby maintains the container in erected condition.
While the arrangement disclosed in U.S. Pat. No. 5,752,648 provides a simple and effective self locking system for holding the container in its erected condition, the thickness of the material of the webs causes them to take a slightly "rounded over" shape as they are pulled down into the notches 30, and they tend to exert a pull on the roll over flap in a direction to disengage it. Additionally, in order to insure that the webs and related components can be operatively engaged with one another, specific dimensional relationships are maintained between the distance from the bottoms of the notches to the bottom of their associated panels 24, and the distance which the relief slits 37 extend above the cut lines 36 and 38, i.e., the length of the relief slits is slightly exaggerated, contributing to a "loose" fit between the components of the self locking arrangement.
Accordingly, there is need for a self locking arrangement that provides a tight, secure fit between components, insuring that a container incorporating the arrangement reliably remains in its erected condition.


A registration system for a printing device and a method for controlling the same are disclosed. For example, the registration system includes a lead screw motor, a lead screw coupled to the lead screw motor, and a carriage coupled to the lead screw. The carriage includes two drive rollers, wherein each drive roller is coupled to a respective splined shaft coupled to a respective yoke, wherein the respective yoke is coupled to a drive pulley and a drive motor that is in a fixed position, wherein movement of the carriage causes the respective splined shaft of the two drive rollers to move guided by the respective yoke.

Printing devices can be used to print images on print media. The print media can be fed through the printing device along a transport path and imaging path to have the image printed. Along the transport path and the imaging path, there are certain locations where processing errors can occur that can cause a misalignment of the image relative to the print media.
For example, the print device can have a registration system. The registration system may be responsible for correctly feeding the print media to an imaging system such that the printed image is correctly aligned with the print media. Some registration systems use a carriage that moves drive rollers and motors of the drive rollers which can have a large amount of total weight. The large amount of weight attached to the carriage can cause inefficiencies due to high amounts of inertia and increased wear.
For example, the high amounts of inertia may cause a hysteresis when the carriage is started or stopped. As a result, the speed of the carriage is slowly increased and decreased as the carriage moves to a desired location. In addition several small adjustments may be made as the carriage over shoots or under shoots the desired location due to the high amount of inertia.

Registration system with a spline and yoke


The present invention relates to a cytokeratin 8/18 complex-specific autoantibody or a fragment comprising an antigen-binding site (paratope) thereof, the use thereof in the diagnosis of breast cancer, a polypeptide having an amino acid sequence of an epitope specifically binding to the autoantibody, a composition for diagnosing breast cancer comprising an agent capable of measuring an expression level of the autoantibody or the fragment comprising an antigen-binding site thereof, a hybridoma cell line producing the autoantibody, and a kit for diagnosing breast cancer comprising the composition of the present invention. Further, the present invention relates to a method for diagnosing breast cancer, comprising the step of detecting the cytokeratin 8/18 complex-specific autoantibody or the fragment comprising the antigen-binding site thereof using the composition of the present invention, and a method for screening a therapeutic agent for breast cancer using the autoantibody.

The present invention relates to a cytokeratin 8/18 complex-specific autoantibody or a fragment comprising an antigen-binding site (paratope) thereof, use thereof in the diagnosis of breast cancer, a polypeptide having an amino acid sequence of an epitope specifically binding to the autoantibody, a composition for diagnosing breast cancer comprising an agent capable of measuring an expression level of the autoantibody or the fragment comprising an antigen-binding site thereof, a hybridoma cell line producing the autoantibody, and a kit for diagnosing breast cancer comprising the composition of the present invention. Further, the present invention relates to a method for diagnosing breast cancer, comprising the step of detecting the cytokeratin 8/18 complex-specific autoantibody or the fragment comprising the antigen-binding site thereof using the composition of the present invention, and a method for screening a therapeutic agent for breast cancer using the autoantibody.
Breast cancer has the highest incidence rates among various cancers in most OECD countries. In Korea, the incidence has also been increasing, concurrent with rising prevalence of obesity and the Westernization of dietary habits. Diagnosis of breast cancer is usually made by mammography, ultrasonography, and Magnetic Resonance imaging (MRI). Mammography is an X-ray examination of the compressed breast, and is useful for detection of small breast cancers. However, many Korean women have less fatty tissue and denser fibrous tissue, and thus it is difficult to detect calcification as an early warning sign of breast cancer. Therefore, a mammogram is usually performed together with ultrasonography which is useful for the detection of solid and cystic breast masses. These mechanical examinations are conducted by a simple examination procedure, but have limited detection accuracy because they rely on a reader's subjective interpretation. Therefore, subsequent tissue biopsy is required. Such tissue biopsy is an invasive method including examination of breast cancer-specific protein expression in the tissue or tissue observation, and requires considerable costs while imposing emotional, physical, and economic burdens on patients. In order to overcome these drawbacks, there is a need to develop an easy and simple diagnostic method for breast cancer.
Meanwhile, the immune system is constructed as a peculiar system distinguishing the self from non-self at an early stage of development, and develops to induce antigen-antibody reaction (humoral immune response) and cellular immune response against foreign antigens only which are exposed to the immune system under normal conditions. However, the generation of antibodies against self-antigens was observed in specific diseases, which is attributed to extracellular release of intracellular antigens due to abnormal expression site of the corresponding antigens, modification of forms, or other aberrant characteristics. Since the 1970s, it has been also reported that the generation of autoantibodies against cancer cell-derived antigens is observed in carcinogenesis, accompanied by abnormal tumor growth, and they are called tumor-associated antigens and tumor-associated autoantibodies. Autoantibodies generated by tumor-associated antigens pre-exist and are found before the onset of disease, suggesting the availability as a biomarker for the early diagnosis.
Until now, various tumor-associated antigens have been identified. Among them, overexpression of HER-2/neu oncoprotein found in 20-30% of breast cancer patients is known to induce autoantibodies, and a tumor suppressor protein p53 is also reported to induce autoantibodies. The cell proliferation-associated proteins, cyclin B1 and CENP-F (centromere protein F) are also known to induce autoantibodies. These results suggest the presence of autoantibodies against a larger number of tumor-associated antigens, and many trials have been made to screen tumor-associated autoantibodies that can be utilized as a cancer biomarker.
For identification of tumor-associated autoantibodies, SEREX (selological analysis of recombinant cDNA expression libraries of human tumors with autologous serum), which is a conventional method of searching autoantibodies by analyzing reactivity of cancer patient sera with cancer cell-derived gene expression libraries, has been used. However, it is difficult to express cancer cell-derived proteins with maximal diversity at the library level. In addition, even after transcription, final protein products undergo posttranslational modification (PTM) such as phosphorylation and glycosylation, which is not reflected in the protein expression libraries. Therefore, the method is not sufficient to detect autoantigens. Alternatively, proteomics-based identification of autoantibodies has been recently conducted. The proteomics-based method includes the procedures of performing two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) of cancer cell-derived proteins, detecting protein spots showing reactivity using cancer patient serum as an autoantibody sample, and identifying the proteins by mass spectrometry, and is commonly abbreviated to SERPA (serological proteome analysis). MAPPING (multiple affinity protein profiling) is also used, in which an affinity chromatography resin is conjugated with antibodies isolated from the patient blood, and cancer cell-derived proteins are applied thereto to identify binding proteins by mass; spectrometry. In addition, cancer cell lysates are separated into several thousand individual fractions to fabricate a protein chip, and the reactivity of patient blood thereto is examined to identify autoantibodies. Such various proteomics-based identification methods are advantageous in that the reactivity of antibodies against cancer cell-derived proteins with posttranslational modifications (PTM) can be directly examined, and thus are able to identify autoantibodies that cannot be identified by SEREX.
However, the above methods still include other limitations. First, there is a problem in the quantity of antibodies. When an analyte is a mixture of two or more components, a relatively large amount of the analyte takes precedence over other analyte in the analysis. This means that minorities are possibly excluded from the analyzable range. In this context, a patient's serum is a mixture of numerous antibodies, an analytically measurable range is determined by the differences in quantity of the constituting autoantibodies and their affinity for antigens, and therefore analysis on the desired autoantibodies could be impractical. Second, due to the dependence of the autoantibody samples to be analyzed on a patient, there is a limitation in the systematic analysis of autoantibody production according to carcinogenesis, and there is also difficulty in collecting a large enough amount of blood samples from patients, which becomes an obstacle to further studies. Finally, there is a problem in the preservation of epitopes reacting with antibodies. According to the current immunological knowledge, there are two types of epitopes, sequential epitopes and conformational epitopes. In vivo induction of antigen-specific antibody production reflects an antigen being encountered by the immune cell antibody for the first time, which means that the antigen-antibody reaction occurs in a solution, and the antigen protein has a structure of maintaining its solubilized form in the blood. Thus, ex vivo test of antigen-antibody reaction is preferably performed in the solution, because their natural binding pattern is well reflected in the solution. In the above mentioned SERPA, however, two-dimensional electrophoresis is performed for the analysis of a protein mixture. That is, proteins to be analyzed are denatured by using SDS and urea, and then their reaction with antibodies is examined. Thus, if the epitope is a sequential epitope, it is detectable, but if the epitope is a conformational epitope, not detectable.
Although the previous studies on autoantibodies suggested their availability as a carcinogenesis-associated maker, their diagnostic effects are not satisfactory, and there is still a limitation in the availability of autoantibodies as a biomarkers for cancer diagnosis. Further, the autoantibody detection methods have limitations in practical application because they do not include a large number of cases or do require excessive experiments. Actually, there are still difficulties in the identification of autoantibodies as a diagnostic marker for cancer.

Marker comprising anti-CK8/18 complex autoantibody and its use for diagnosing cancer


Improved compositions of benzoyl peroxide are prepared by at least partially dissolving benzoyl peroxide in diethylene glycol monoethyl ether to prepare a premixture which forms a flocculent composition of benzoyl peroxide when admixed with water or an aqueous medium. The improved benzoyl peroxide compositions have a small particle size compared with those prepared by conventional grinding techniques and the time and potential hazards associated with grinding are avoided. The small particle size of the benzoyl peroxide flocculents result in increased surface area of active ingredient on the skin for a given concentration of benzoyl peroxide. The flocculent compositions are used to prepare compositions for the topical treatment of acne or other dermatological disorders.

1. Field of the Invention
The present invention has to do with improved compositions of benzoyl peroxide and methods of processing benzoyl peroxide. More particularly, the invention relates to the use of a composition such as TRANSCUTOL.RTM. diethylene glycol monoethyl ether as a processing aid for making a new benzoyl peroxide premixture which can be admixed with an aqueous medium to make a new benzoyl peroxide flocculent composition.
2. The Related Art
Benzoyl peroxide is most commonly employed as an active ingredient in topical compositions which are used in the treatment of acne and other dermatological conditions. Topically applied compositions used to treat the skin normally require that the benzoyl peroxide be ground to a fine particle size in a suitable vehicle before use. If the benzoyl peroxide is not ground, the product will be grainy and scratchy on the skin. Moreover, the clinical efficacy as related to the surface area of active ingredient on the skin, which in turn is a function of particle size, would be expected to be reduced for a given concentration of benzoyl peroxide when larger particles are employed. It is also known that benzoyl peroxide is a potentially explosive oxidizing agent and it must be ground under controlled conditions in a medium that prevents excessive heat build-up. Current manufacturing processes, therefore, are difficult, time consuming and potentially hazardous.
Benzoyl peroxide containing acne treatment compositions are disclosed in U.S. Pat. No. 4,606,913. The patent has to do with high internal phase emulsions and their use as suspending mediums for cosmetics and drugs. The emulsions are the water-in-oil type and, as an example, they can be used to make an acne cream comprised of water, mineral oil and benzoyl peroxide. The patent also discloses various cosmetic adjunct materials which can be used when the high internal phase emulsions are employed as a vehicle for cosmetic ingredients and these include solvents such as ethylene glycol monoethyl ether, diethylene glycol monoethyl ether, diethylene glycol monobutyl ether and several others. The compositions are prepared by adding the aqueous phase to the oil phase. Ingredients that are part of the aqueous phase are added into the aqueous phase before the phases are brought together.
Antiacne compositions combined with sun filters are disclosed in U.S. Pat. No. 4,671,956. The compositions are for the local treatment of acne and they contain from 0.5% to 20% by weight of benzoyl peroxide in association with at least one sun filter. The benzoyl peroxide is used in the form of a finely divided powder in the dry or moist state, preferably in the moist state. The antiacne compositions are in the form of emulsions and are prepared by adding benzoyl peroxide in the aqueous phase and the sun filter either in the aqueous phase or oil phase depending on its affinity. Propylene glycol is disclosed as an ingredient of the compositions as a humectant and solvents such as lower aliphatic alcohols can be incorporated in gel-type preparations.
According to U.S. Pat. No. 5,019,567, quaternary ammonium lipophilic salicylates are combined with benzoyl peroxide to prepare compositions for the treatment of dermatoses, acne, warts, skin dyskeratinization, cutaneous ulcers and other cutaneous disorders. The patent exemplifies gel compositions which include diethylene glycol monoethyl ether as an ingredient, among others, but there is no disclosure of the method of preparing the gel.
We have now discovered an improved method of processing benzoyl peroxide to make a premixture which can be admixed with an aqueous medium to make a new flocculent composition. The flocculent composition itself feels smooth or impalpable when rubbed on the skin. Our method is easier, faster and safer than conventional techniques which employ grinding to reduce the particle size of the benzoyl peroxide and the particles of benzoyl peroxide in our flocculent composition are substantially smaller than those which are obtained by conventional grinding.

Benzoyl peroxide flocculent materials and methods of their preparation


A size adjustable wrench socket is disclosed which has a plurality of jaws which are slidably engaged within a jaw guide for moving radially inward and outward relative to the jaw guide for fitting threaded fasteners of various sizes. A controller sleeve is configured for engaging upwardly extending protuberances of the jaws, such that rotation of the controller sleeve in various directions will moved the jaws inward and outward relative to the jaw guide. The jaws further include a plurality of upwardly extending teeth which are formed into planar shoulders of intermediate portions of the jaws. A latch member is provided having a planar surface from which a plurality of teeth downwardly extend for engaging the upwardly extending teeth of the planar shoulders of the intermediate portions of the jaws. The latch member is movable from a latched position to a released position. When disposed in the latched position, the teeth of the latch member engage the upwardly extending teeth of the jaws to latch the jaws in a fixed position relative to the jaw guide. In the released position, the teeth of the latch member are spaced apart from the teeth of the jaws such that the jaws are movable relative to the jaw guide. The teeth of the jaws and the jaw guide are sized to provide indexed positions at which the jaws are spaced apart to correspond with predetermined, standard sizes of drive heads for threaded fasteners.

Wrench sockets have been utilized for applying torque to nuts and the heads of bolts of threaded fasteners. Often, ratchet-type wrench drivers are utilized as drive members for coupling to the wrench sockets to provide driving torque. Prior art wrench sockets have included both wrench sockets of fixed size and wrench sockets having size-adjustable jaws, which may be adjusted for accommodating fastener heads of various sizes. As used herein, the term fastener head includes either a nut or a bolt head, such as that having an hexagonally shaped profile which defines drive surfaces that may be engaged by a wrench socket for transferring torque from the wrench socket to the threaded fastener. Size adjustable wrench sockets have been used both with wrench drivers which have handles that extend at angles such as ninety degrees to an axis of rotation of the wrench sockets, and with in-line drivers in which the handles extend in-line with the axis of rotation of the wrench sockets, such as nut drivers and the like.
Prior art size adjustable wrench sockets have included size adjustable jaws which are mounted to jaw guide members having guide surfaces upon which portions of the jaws slidably engage. These prior art wrench sockets have also included upwardly extending members which engage within slotted collars which are rotatably mounted above the jaw guide members for rotating to move the jaws radially inward and radially outward until the spacing between the jaws is such that torque may be transferred from the wrench sockets to the threaded fasteners. Bias springs have been utilized to bias the jaws to into radially outward positions relative to the jaw guides. Some prior art size adjustable wrench sockets have been continuously adjustable, over continuous ranges of sizes. Other size adjustable wrench sockets have been provided with indexed settings, which correspond to standard sizes of threaded fastener. However, prior art size adjustable wrench sockets have typically proven unsatisfactory in that they fail to provide wrench sockets of adequate strength for remaining engaged with fastener heads when large amounts of torque are applied to the wrench sockets and the fastener heads.


A microfluidic device is provided for regulating the temperature of a sample fluid flowing therethrough, as well as, a method of regulating the temperature of the sample fluid flowing through the microfluidic device. The microfluidic device includes a body member defining a fluid channel for allowing the sample fluid to flow therethrough and a first regulating channel. A regulating fluid having a predetermined temperature flows through the regulating channel adjacent the fluid channel so as to effectuate a heat exchange with the sample fluid flowing through the fluid channel to regulate the temperature thereof.

As is known, microfluidic systems are being used in an increasing number of applications, including biological applications. These microfluidic systems are becoming more popular for several reasons. By way of example, it can be appreciated that microfluidic devices utilize very small volumes of fluids. Consequently, since such small volumes of fluid are used in microfluidic devices, it is more cost effective to do experiments that require very expensive reagents in microfluidic devices than in prior macro systems.
Often times, the various types of chemical and biological experiments conducted with microfluidic devices require controlled temperatures (e.g. PCR). In other words, these various chemical experiments require biological objects to be maintained at either constant temperatures or to be cycled so as to expose the biological object to various predetermined temperatures.
Currently, temperature control in microfluidic devices is accomplished using conventional external heating elements and/or cooling elements. These conventional heating and/or cooling elements require power sources such as batteries or the like. The use of such temperature control mechanisms not only adds significantly to the overall cost of the microfluidic device, such heating and cooling elements are often considerably larger than the microfluidic device itself. This, in turn, may render the microfluidic system too heavy or too large to be attractive to potential users. As such, it is highly desirable to provide a method and apparatus for controlling temperature in a microfluidic device that requires that no external power source.
It can be appreciated that various types of chemical reactions have corresponding endothermic or exothermic properties. While these reactions are sometimes performed with quite volatile chemistries that make for unsafe conditions at the macroscale, at the microscale, the small volumes required reduce the hazard and increase the practicality. In addition, chemical heat generation is more efficient than traditional heating methods (such as resistive heating). Consequently, utilizing the endothermic or exothermic properties of chemical reactions in temperature control becomes possible.
Therefore, it is a primary object and feature of the present invention to provide a method and apparatus for controlling a temperature of a sample fluid in a channel of a microfluidic device that requires no external power source.
It is a further object and feature of the present invention to provide a method and apparatus for controlling the temperature of a sample fluid in a channel of a microfluidic device that is less expensive than prior temperature control mechanisms for microfluidic devices.
It is a still further object and feature of the present invention to provide a method and apparatus for controlling a temperature of a sample fluid flowing through a channel of a microfluidic device that is simple and inexpensive to utilize.
In accordance with the present invention, a microfluidic device is provided for regulating the temperature of a sample fluid. The microfluidic device includes a body member defining a fluid channel for receiving the sample fluid therein and a first regulating channel. A regulating fluid having a predetermined temperature is provided in the first regulating channel. The regulating fluid effectuates a heat exchange with the sample fluid in the fluid channel.
In a first embodiment, the fluid channel has an outer periphery and the first regulating channel extends about the outer periphery of the fluid channel. In a second embodiment, the fluid channel extends generally along a longitudinal axis and the first regulating channel includes a first portion being a first predetermined distance from the fluid channel and a second portion being a second predetermined distance from the fluid channel.
The body member may include a maintenance channel and the microfluidic device may include a maintenance fluid in the maintenance channel. The maintenance fluid effectuates a heat exchange with the regulating fluid in the first regulating channel so as to maintain the temperature thereof. The first portion of the first regulating channel is a third predetermined distance from the maintenance channel and the second portion of the first regulating channel is a fourth predetermined distance from the maintenance channel. The body member may also include a second regulating channel having a second regulating fluid therein. The second regulating fluid has a temperature and effectuates the heat exchange with the sample fluid in the fluid channel. The second regulating channel includes a first portion being a first predetermined distance from the fluid channel and a second portion being a second predetermined distance from the fluid channel.
The body member may also include a first maintenance channel having a first maintenance fluid therein. The first maintenance fluid effectuates a heat exchange with the regulating fluid in the first regulating channel so as to maintain the temperature thereof. Similarly, the body member may include a second maintenance channel having a second maintenance fluid therein. The second maintenance fluid effectuates a heat exchange with the second regulating fluid in the second regulating channel so as to maintain the temperature thereof.
In accordance with a further aspect of the present invention, a microfluidic device is provided for regulating a temperature of a sample fluid. The microfluidic device includes a body member having a flow channel therethrough for receiving the sample fluid. A temperature regulating structure is provided within the body member. The temperature regulating structure includes a regulating fluid of a predetermined temperature therein for effectuating a heat exchange with the sample fluid in the flow channel.
The temperature regulating structure may wind around the flow channel at a predetermined distance therefrom. Alternatively, the temperature regulating structure may include a regulating channel passing through the body member. The regulating channel has a first portion being a first predetermined distance from the flow channel and a second portion being a second predetermined distance from the flow channel. The temperature regulating structure may also include a second regulating channel passing through the body member. The second regulating channel has a first portion being a first predetermined distance from the flow channel and a second portion being a second predetermined distance from the flow channel. The temperature regulating structure includes a second regulating fluid therein for effectuating a heat exchange with the sample fluid in the flow channel.
The temperature regulating structure may include a first maintenance channel passing through the body member having a first maintenance fluid therein. The first maintenance fluid in the first maintenance channel effectuates a heat exchange with the regulating fluid in the first regulating channel so as to maintain the predetermined temperature thereof. A second maintenance channel may also extend through the body member. The second maintenance channel has a second maintenance fluid therein. The second maintenance fluid effectuates a heat exchange with the second regulating fluid in the second regulating channel so as to maintain the predetermined temperature thereof.
In accordance with a still further object and feature of the present invention, a method of regulating the temperature of a sample fluid in a microfluidic device is provided. The method includes the steps of providing the sample fluid in a first channel within the microfluidic device and positioning a regulating fluid having a predetermined temperature adjacent the first channel so as to effectuate a heat exchange between the regulating fluid and the sample fluid.
The distance between the regulating fluid and the first channel may be varied. A first maintenance fluid having a predetermined temperature may be positioned adjacent the regulating fluid to maintain the predetermined temperature thereof. A second regulating fluid having a predetermined temperature may be positioned adjacent the first channel so as to effectuate a heat exchange between the second regulating fluid and the sample fluid. The distance between the second regulating fluid and the first channel may be varied. A second maintenance fluid having a predetermined temperature may be positioned adjacent the second regulating fluid to maintain the predetermined temperature thereof.

Method and apparatus for temperature control of a microfluidic device


A compact and portable bowling ball cleaner apparatus has a controlled heated temperature/timed steam process that properly and effective removes oil and dirt from the pores and surface of reactive bowling balls and gives restored life and performance to the ball without changing the coverstock or mechanics. The cleaner apparatus is not only cost effective, but a must have product for any avid/league/pro bowler that uses reactive bowling balls. The cleaner apparatus provides an effective, safe, affordable, user friendly, compact and attractive solution for removing oil and dirt from bowling balls.

The present invention relates to apparatus and methods for cleaning bowling balls and, more particularly, to an electrically driven aluminum structured sweat box that removes oil and dirt from bowling balls.
Oil build up on bowling balls (typically made of plastic, reactive resin, urethane, or a combination thereof) causes the bowling ball to lose its performance capability and "hookability" over time, which is the most important function of a reactive bowling ball. Reactive bowling balls have cores inside the ball which is dynamically imbalanced to cause the ball to try to stabilize as it is rolling down the bowling lane. This makes the ball roll over a different point on the surface every time it revolves and flares or causes multiple rings of oil as it travels down the lane. Over time, this oil builds up and clogs the pores of the bowling ball. In order to maintain maximum performance, these types of bowling balls must have the oil and dirt accumulation extracted from the pores in order to function at the highest performance potential for which it was designed.
There are many horror stories of how to remove oil from bowling balls. People have desperately tried all sorts of things, from putting the ball in ovens, cat litter, dishwashers, microwaves, heat lamps, sitting in the sun for hours, putting in a hot car trunk in hot summer heat, soaking it in a bucket or tub of hot water, and the like. None of these processes, however, are the most effective way of removing dirt and oil from the bowling ball; nor are they good for the bowling ball.
A conventional dry heat process is used for cleaning bowling balls. This process, however, is known to remove some of the plasticizers from the ball, which is undesirable because the plasticizers help the reactive ball to "hook". This process is often performed in pro shops because of its cost, large size and unavailability for home use to the general bowling public (league, casual, pro bowlers, etc.). Additionally, pro shops can charge, for example, $30-50 per visit to put a bowling ball through this cleaning process. Pro Shops are also far, few and in between, making it inconvenient for bowlers to get the proper maintenance for their bowling balls as recommended.
Another conventional system provides a hot water bath (immersing the ball completely in water) for the bowling ball to be cleaned in. Such systems, however, may result in water not getting fully removed from the ball, for example, staying in the finger holes of the ball and getting into the pores, resulting in the user having to wait before use for the ball to dry, or try to manually dry the ball after cleaning.
As can be seen, there is a need for an improved method and system for removing dirt and oil from a bowling ball. There is also a need to make this method/equipment available to the general bowling public.

Apparatus and method for cleaning bowling balls


Mismatch errors within oversampled analog to digital (ADC) and digital to analog (DAC) data converters limit the overall conversion accuracy. A circuit is provided which interchanges the analog segments within a multibit oversampled converter in a fashion to move the mismatch errors away from the overall converter's passband frequencies and towards other frequencies where they do not interfere with the signal to be converted. The circuit works by minimizing the differences in the signals which control the individual segments. Circuits may be provided for achieving first, second and higher order "shaping" of the mismatch errors. The invention also provides a circuit in which exchange of the analog elements with the DACs of multibit oversampled converters is effected using a circular queue, so moving the mismatch errors to high frequency where they do not interfere with the signal to be converted.

1. Field of the Invention
This invention relates to data conversion. The invention is particularly directed to analog to digital converters (ADC) and digital to analog converters (DAC). The invention is especially directed to the minimisation of error in data converters of these kinds.
2. Description of the Prior Art
Multibit oversampled analog to digital (ADC) and digital to analog (DAC) data converters are an attractive alternative to their single bit counterparts because of their reduced quantisation error and the relative ease of achieving loop operation which is stable and free of spurious tones. Recent work on sigma delta (.SIGMA..DELTA.) oversampled data converters has shown how averaging techniques can be used to extend the overall accuracy beyond the limits set by process-induced mismatch between the analog segments in the multibit converter. These averaging schemes in effect "noise-shape" the mismatch error away from the passband of interest. The effect of this noise shaping is illustrated qualitatively in FIGS. 1 and 2. FIG. 1 shows, on a plot of signal amplitude against frequency, the effect of segment mismatch errors, which result in harmonics of the signal to be converted being erroneously added to the passband of the converter. FIG. 2 shows the desired noise shaping effect, where the errors have been moved to a higher frequency and no longer interfere with the signal passband.
More recently, second order shaping of the mismatch error has been described, in which a multi-strand sigma delta (.SIGMA..DELTA.) loop is employed to noise-shape a vector of quantisation errors. Each strand of the loop controls a segment in the multibit DAC and applies a noise-shaping filter to its component of the quantisation error vector.
The term "noise-shaping" in the sigma-delta converter art has been used in reference to increasing the sampling rate to move the quantisation error signal away from the frequency of interest. In the present specification, the term "noise-shaping" is also applied to techniques directed to overcoming the impact of errors arising out of manufacturing tolerances in the components of sigma-delta systems, and is to be understood accordingly.

Reduction of mismatch errors for multibit oversampled data converters


Cascaded object detection techniques are described. In one or more implementations, cascaded coarse-to-dense object detection techniques are utilized to detect objects in images. In a first stage, coarse features are extracted from an image, and non-object regions are rejected. Then, in one or more subsequent stages, dense features are extracted from the remaining non-rejected regions of the image to detect one or more objects in the image.

Detecting faces in uncontrolled environments continues to be a challenge for conventional face detection solutions due to the large variations in facial appearances. Conventional object detection processes often are sliding-window and model-based, and hence are limited in handling large variations in facial appearances.
The background description provided herein is for the purpose of generally presenting the context of the disclosure. Work of the presently named inventors, to the extent the work is described in this background section, as well as aspects of the description that may not otherwise qualify as prior art at the time of filing, are neither expressly nor impliedly admitted as prior art against the present disclosure.


A low-voltage protective device includes: at least one outer conductor path from an outer conductor power terminal of the low-voltage protective device to an outer conductor load terminal of the low-voltage protective device; a neutral conductor path from a neutral conductor terminal of the low-voltage protective device to a neutral conductor load terminal of the low-voltage protective device; a mechanical bypass switch arranged in the outer conductor path; a first semiconductor circuit arrangement connected in parallel to the mechanical bypass switch, the first semiconductor circuit arrangement having at least one power semiconductor, such as an IGBT, with a control terminal, such as a gate terminal; an electronic control unit; a current-measurement arrangement arranged in the outer conductor path, connected to the electronic control unit of the protective device; and at least one voltage measurement arrangement for detecting a Miller effect-induced voltage spike at the at least one power semiconductor.

A corresponding protective device is known from WO 2015/028634 A1 of the applicant. When the protective device is switched off, first the bypass switch is opened, such that an arc occurs and the current commutates to the semiconductor circuit arrangement. Subsequently, the previously energized semiconductor circuit arrangement is switched off and the break contacts are opened to provide galvanic isolation. These break contacts are connected in series with the bypass switch.
When a short-circuit current is interrupted, it is important that the contacts of the bypass switch are opened far enough that an no arc is ignited at the contacts of the bypass switch when the short-circuit current is interrupted. At the same time, however, the short-circuit current should be interrupted as quickly as possible in order to minimize the load in the downstream network, as well as in the semiconductor circuit arrangement. With an early and/or rapid interruption of the short-circuit current, it is possible to interrupt the current in the rising phase, even before it reaches its maximum amplitude determined by the internal resistance of the supply network, as well as the resistance of the downstream network—thereby making it possible to further minimize the load on the network and devices.
Activating the bypass switch electrically and/or electromagnetically, so that its contacts open, is a known practice. A timer is started at the same time. It is assumed in this case that after a certain period of time, the contacts of the bypass switch are opened wide enough that they can safely interrupt the short-circuit current, and they have assumed a sufficiently stable and/or static state. This period of time must be adapted with safety factors to ensure that the contacts of the bypass switch are actually opened widely enough. These safety factors must be both of the necessary size and accordingly sufficient—due to significant variations in the opening behavior of mechanical switches. The result is late interruption of the short-circuit current and a correspondingly high load on the network and the semiconductor circuit arrangement.


The invention provides a method of making a transducer activated tool tip, comprising, providing a substantially linear tip body having a fluid inlet end and a fluid outlet end. The tip body has an inlet end and a subgingival outlet end. The tip body is bent in a first direction. In the tip body is formed a fluid passageway internal to the tip. The tip body is bent in a second direction, which is opposite to the first direction.

The invention relates to a transducer activated tool for contacting tooth surfaces and directing a fluid adjacent to the tooth. More particularly, the invention relates to an improved strength ultrasonically activated tool. The tip includes a passageway for directing a fluid onto the dental or tip surfaces. The tip is made by bending the tip at the location for the opening of the passageway, before drilling the passageway. Preferably the end of the tip is adapted for subgingival insertion, and has an outer diameter of less than 0.03 inch within 0.03 inch of the end of the tip. During subgingival insertion the subgingival end of the tip extends between the patient""s gum and the subgingival tooth surface, and delivers a focused spray of fluid onto the subgingival tooth surface.
The method of the invention includes bending a tip at least twice. This allows a passageway to be placed in different pre-selected locations. The passageway in a prior art subgingival tip is drilled in the straight tip at a slight angle producing a long exit hole. The passageway in a prior art subgingival tip opens into a hole which crosses high stress areas. The invention allows the hole to be positioned more easily and allows control of the length of the hole independent of the hole location on the tip. The first step is to bend a straight tip which does not have a passageway therethrough. The second step is to drill a passageway through the tip from the fluid inlet end of the tip generally along the straight portion of the tip to the bend. The location of the bend controls the location of the passageway opening (or exit hole) and the bend angle (and bend radius) controls the length of the exit hole. Finally the tip is bent in the opposite direction. The tip may be angled before the final bend is made. Preferably the passageway is concentric relative to the straight tip, the hole could be off center and/or on a slight angle to the tip central line to produce a long exit hole. In addition a short bend with an offset bend gives a very long groove. Alternatively, multiple bends are made in the tip before drilling the passageway to produce various exit hole shapes (or multiple exit holes). Preferably the exit hole is positioned near to the end of the tip. Preferably the exit hole edge is kept away from the high stress area located near the end of the tip and the exit hole is kept short enough to avoid the high stress area near the base of the tip.
Many useful dental instruments employ substantial vibratory motion at a tool tip of the instrument for cleaning, scaling and like operations. The tool tips are designed to produce flexural and longitudinal vibrations with flexural motions of from about 0.02 to 0.2 mm. The tip is typically attached to an electro-mechanical part or section that can be induced to vibrate at high frequency. The instrument is driven by an electronic generator at relatively high frequencies, typically on the order of above 20 kHz, to obtain adequate motion and to minimize objectionable noise since the human hearing threshold is about 18 kHz. The energy generator and related electro-mechanical section may be any one of several types such as electro-dynamic, piezo electric, or magnetostrictive. Design of the tip and its related electro-mechanical components involves combining a number of parameters to produce mechanical resonances (harmonic vibrations) at the driving frequency to produce amplified mechanical motion, particularly at the distal tip end.
Dao et al in U.S. Pat. No. 5,749,727 disclose transducer activated subgingival tool tip, and the disclosure thereof is incorporated herein by reference in its entirety. In use the vibrating tip is guided over and about tooth surfaces by the operator. The tip must be capable of penetrating between teeth and under or below the gingival or gum line. Generally, the tip must be small in cross-section, ideally having a pointed tip with a tapered cross-section extending about 2.5 to 5 mm back from the distal tip end to allow adequate access between teeth and gingival. More preferably the tapered cross-section extends about 10 mm from the distal tip end.
The prior art does not provide a method of making an insert for an ultrasonically activated subgingival tooth cleaning tool, comprising: bending a solid metal tip to form a bend at a location for an opening of a passageway, then drilling the passageway through the solid metal tip to form a tip having a passageway having an opening at the bend, as is provided by the present invention.
The prior art does not provide a method of making a transducer activated tool tip, comprising, providing a substantially linear tip body having a fluid inlet end and a fluid outlet end, wherein the tip body is bent in a first direction so that a centerline through the fluid outlet end intersects a centerline through the fluid inlet end at an angle greater than 5 degrees and then in the tip body is formed a fluid passageway internal to the tip, having an inlet end and a subgingival outlet end, then the tip body is bent in a second direction so that a centerline through the fluid outlet end intersects a centerline through the fluid inlet end at an angle of substantially 0 degrees, and the tip body is bent further in the second direction so that the centerline through the fluid outlet end intersects the centerline through the fluid inlet end at an angle greater than 5 degrees, as is provided by the present invention.
It is an object of the invention to provide a method of making an insert for an ultrasonically activated subgingival tooth cleaning tool, comprising: bending a solid metal tip to form a bend at a location for an opening of a passageway, then drilling the passageway through the solid metal tip to form a tip having a passageway having an opening at the bend.
It is an object of the invention to provide a transducer activated tool for contacting subgingival tooth surfaces and directing a fluid adjacent to the subgingival surfaces, comprising an activated tip has a fluid inlet end, a subgingival outlet end, and a fluid passageway wall internal to the tip. The fluid passageway wall has an average passageway diameter. The fluid passageway wall ends at an edge providing a fluid discharge orifice formed in a discharge side of the subgingival outlet end of the tip. The subgingival outlet end has an opposite side positioned opposite to the discharge side. The discharge side has a discharge side outer surface whereby a first line tangential to the discharge side outer surface of the fluid inlet end, and a second line tangential to the discharge side outer surface of the subgingival outlet end intersect to form an angle of less than 180 degrees facing outwardly from the discharge side outer surface.
It is an object of the invention to provide a transducer activated tool for contacting tooth surfaces and directing a fluid adjacent to the surfaces, comprising an activated tip has a fluid inlet end, a outlet end, and a fluid passageway wall internal to the tip, the activated tip has a tip centerline, the fluid passageway wall ends at an edge providing a fluid discharge orifice formed in a discharge side of the outlet end of the tip, the outlet end has an opposite side positioned opposite to the discharge side. The discharge side has a discharge side outer surface whereby a line uniformly offset from the tip centerline on the discharge side outer surface forms an angle of less than 180 degrees outwardly from the discharge side outer surface. The transducer activated tool is formed from a preformed body of the tool wherein the opposite side has an opposite side outer surface whereby a line uniformly offset from the tip centerline on the opposite side outer surface forms an angle of less than 180 degrees outwardly from the opposite side outer surface.
It is an object of the invention to provide a transducer activated subgingival tool for contacting subgingival tooth surfaces and directing a fluid adjacent to the surfaces, comprising an activated tip has a fluid inlet end, a subgingival outlet end, and a fluid passageway wall internal to the tip, the fluid passageway wall ends at an edge providing a fluid discharge orifice formed in a discharge side of the outlet end of the tip. The subgingival outlet end has an opposite side positioned opposite to the discharge side. The discharge side has a discharge side outer surface whereby a line on the discharge side outer surface forms an angle of less than 180 degrees outwardly from the discharge side outer surface. The transducer activated subgingival tool is formed from a preform of the tool. The opposite side has an opposite side outer surface whereby a line on the opposite side outer surface forms an angle of less than 180 degrees outwardly from the opposite side outer surface.
It is an object of the invention to provide a preformed tool for making a transducer activated subgingival tool for contacting subgingival tooth surfaces and directing a fluid adjacent to the surfaces, comprising an activated tip has a fluid inlet end, a subgingival outlet end, and a fluid passageway wall internal to the tip formed in the inlet end generally along the longitudinal center axis of the inlet end of the tip. The subgingival outlet end has a discharge side and an opposite side. The opposite side is opposite to the discharge side. The opposite side has an outer surface which forms an angle of less than 180 degrees. The fluid passageway has a central axis which is substantially on the center axis of the inlet end of the tip. The fluid passageway wall ends at an edge providing a fluid discharge orifice formed in the discharge side of the tip.
It is an object of the invention to provide an insert for an ultrasonically activated subgingival tool of a generally axially elongated cylindrical structure comprising a handpiece including a coil for generating an electromagnetic field, the insert is vibrated at high frequency in longitudinal motion in response to the coil, the insert comprising a magnetostrictive element; a connecting body, axially transmitting the high frequency motion from the ultrasonic magnetostrictive element; and a tip, axially attached to the connecting body, that receives the longitudinal motion, has distal surfaces shaped to contact a subgingival tooth surface. The tip comprises a fluid passageway wall extending internally through a substantial portion of the tip, formed generally along the longitudinal center axis of the tip, the tip has an inlet end and a subgingival outlet end, the subgingival end is shaped to contact the subgingival tooth surfaces without damaging the adjacent gum, a 0.03 inch length of the subgingival end of the tip within 0.03 inch of terminus has one or more outer diameters, each of the diameters is is less than 0.03 inch. The fluid passageway wall has an average diameter, an outlet opening diameter, and opens into a groove channel has a groove channel length. The groove channel length is more than 0.5 and less than three times the outlet opening diameter. Preferably the tip passageway orifice exits within a range of about 2-14 mm from the fluid outlet end of the tip.
It is an object of the invention to provide a method of making an insert for an ultrasonically activated subgingival tooth cleaning tool, comprising providing a preformed tool comprising an activated tip has a fluid inlet end, a subgingival outlet end, and a fluid passageway wall internal to the tip, the fluid passageway wall ends at an edge providing a fluid discharge orifice formed in a discharge side of the tip, the fluid discharge orifice is in the discharge side, the tip has an opposite side, the opposite side is opposite to the discharge side, the opposite side has an outer surface which forms an angle of less than 180 degrees outwardly from the opposite side, bending the tip whereby a first line tangential to the discharge side outer surface of the fluid inlet end, and a second line tangential to the discharge side outer surface of the subgingival outlet end intersect to form an angle of less than 180 degrees facing outwardly from the discharge side outer surface.
It is an object of the invention to provide a method of making a transducer activated tool tip, comprising, providing a substantially linear tip body has a fluid inlet end and a fluid outlet end, bending the tip body in a first direction so that a centerline through the fluid outlet end intersects a centerline through the fluid inlet end at an angle greater than 5 degrees, and forming in the tip body a fluid passageway internal to the tip, has an inlet end and a subgingival outlet end, the subgingival outlet end of the tip has a longest cross-sectional dimension of less than 0.03 inch; bending the tip body in a second direction so that a centerline through the fluid outlet end intersects a centerline through the subgingival outlet end at an angle of substantially 0 degrees, continuing to bend the tip body in the second direction so that the centerline through the fluid inlet end intersects the centerline through the subgingival outlet end at an angle greater than 5 degrees.
It is an object of the invention to provide a method of making a transducer activated tool tip for contacting subgingival tooth surfaces and directing a fluid adjacent to the surfaces, comprising, providing a substantially linear tip body has a fluid inlet end and a fluid outlet end, shaping the fluid outlet end to form distal surfaces for contacting the subgingival tooth surfaces; bending the tip body in a first direction so that a centerline through the fluid outlet end intersects a centerline through the fluid inlet end at an angle greater than 5 degrees, and forming in the tip body a fluid passageway internal to the tip, has an inlet end and a subgingival outlet end, the subgingival end extending distally from a step in the outer surface of the tip and is shaped to contact the tooth surfaces, the subgingival outlet end of the tip has a longest cross-sectional dimension of less than 0.03 inch; the passageway wall is offset from the centerline of the tip whereby a discharge orifice is formed by an edge of the passageway wall at a side of the tip, bending the tip body in a second direction so that a centerline through the fluid outlet end intersects a centerline through the fluid inlet end at an angle of substantially 0 degrees, continuing to bend the tip body in the second direction so that the centerline through the fluid outlet end intersects the centerline through the fluid inlet end at an angle greater than 5 degrees.
The invention provides a method of making an insert for an ultrasonically activated subgingival tooth cleaning tool, comprising: bending a solid metal tip to form a bend at a location for an opening of a passageway, then drilling the passageway through the solid metal tip to form a tip having a passageway having an opening at the bend.
The invention provides a transducer activated tool for contacting subgingival tooth surfaces and directing a fluid adjacent to the subgingival surfaces, comprising an activated tip has a fluid inlet end, a subgingival outlet end, and a fluid passageway wall internal to the tip. The fluid passageway wall has an average passageway diameter. The fluid passageway wall ends at an edge providing a fluid discharge orifice formed in a discharge side of the subgingival outlet end of the tip. The subgingival outlet end has an opposite side positioned opposite to the discharge side. The discharge side has a discharge side outer surface whereby a first line tangential to the discharge side outer surface of the fluid inlet end, and a second line tangential to the discharge side outer surface of the subgingival outlet end intersect to form an angle of less than 180 degrees facing outwardly from the discharge side outer surface.
The invention provides a transducer activated tool for contacting tooth surfaces and directing a fluid adjacent to the surfaces, comprising an activated tip has a fluid inlet end, a outlet end, and a fluid passageway wall internal to the tip, the activated tip has a tip centerline, the fluid passageway wall ends at an edge providing a fluid discharge orifice formed in a discharge side of the outlet end of the tip, the outlet end has an opposite side positioned opposite to the discharge side. The discharge side has a discharge side outer surface whereby a line uniformly offset from the tip centerline on the discharge side outer surface forms an angle of less than 180 degrees outwardly from the discharge side outer surface. The transducer activated tool is formed from a preformed body of the tool wherein the opposite side has an opposite side outer surface whereby a line uniformly offset from the tip centerline on the opposite side outer surface forms an angle of less than 180 degrees outwardly from the opposite side outer surface.
The invention provides a transducer activated subgingival tool for contacting subgingival tooth surfaces and directing a fluid adjacent to the surfaces, comprising an activated tip has a fluid inlet end, a subgingival outlet end, and a fluid passageway wall internal to the tip, the fluid passageway wall ends at an edge providing a fluid discharge orifice formed in a discharge side of the outlet end of the tip. The subgingival outlet end has an opposite side positioned opposite to the discharge side. The discharge side has a discharge side outer surface whereby a line on the discharge side outer surface forms an angle of less than 180 degrees outwardly from the discharge side outer surface. The transducer activated subgingival tool is formed from a preform of the tool. The opposite side has an opposite side outer surface whereby a line on the opposite side outer surface forms an angle of less than 180 degrees outwardly from the opposite side outer surface.
The invention provides a preformed tool for making a transducer activated subgingival tool for contacting subgingival tooth surfaces and directing a fluid adjacent to the surfaces, comprising an activated tip has a fluid inlet end, a subgingival outlet end, and a fluid passageway wall internal to the tip formed in the inlet end generally along the longitudinal center axis of the inlet end of the tip. The subgingival outlet end has a discharge side and an opposite side. The opposite side is opposite to the discharge side. The opposite side has an outer surface which forms an angle of less than 180 degrees. The fluid passageway has a central axis which is substantially on the center axis of the inlet end of the tip. The fluid passageway wall ends at an edge providing a fluid discharge orifice formed in the discharge side of the tip.
The invention provides an insert for an ultrasonically activated subgingival tool of a generally axially elongated cylindrical structure comprising a handpiece including a coil for generating an electromagnetic field, the insert is vibrated at high frequency in longitudinal motion in response to the coil, the insert comprising a magnetostrictive element; a connecting body, axially transmitting the high frequency motion from the ultrasonic magnetostrictive element; and a tip, axially attached to the connecting body, that receives the longitudinal motion, has distal surfaces shaped to contact a subgingival tooth surface. The tip comprises a fluid passageway wall extending internally through a substantial portion of the tip, formed generally along the longitudinal center axis of the tip, the tip has an inlet end and a subgingival outlet end, the subgingival end is shaped to contact the subgingival tooth surfaces without damaging the adjacent gum, a 0.03 inch length of the subgingival end of the tip within 0.03 inch of terminus has one or more outer diameters, each of the diameters is less than 0.03 inch. The fluid passageway wall has an average diameter, an outlet opening diameter, and opens into a groove channel has a groove channel length. The groove channel length is more than 0.5 and less than three times the outlet opening diameter. Preferably the tip passageway orifice exits within a range of about 2-14 mm from the fluid outlet end of the tip.
The invention provides a method of making an insert for an ultrasonically activated subgingival tooth cleaning tool, comprising providing a preformed tool comprising an activated tip has a fluid inlet end, a subgingival outlet end, and a fluid passageway wall internal to the tip, the fluid passageway wall ends at an edge providing a fluid discharge orifice formed in a discharge side of the tip, the fluid discharge orifice is in the discharge side, the tip has an opposite side, the opposite side is opposite to the discharge side, the opposite side has an outer surface which forms an angle of less than 180 degrees outwardly from the opposite side, bending the tip whereby a first line tangential to the discharge side outer surface of the fluid inlet end, and a second line tangential to the discharge side outer surface of the subgingival outlet end intersect to form an angle of less than 180 degrees facing outwardly from the discharge side outer surface.
The invention provides a method of making a transducer activated tool tip, comprising, providing a substantially linear tip body has a fluid inlet end and a fluid outlet end, bending the tip body in a first direction so that a centerline through the fluid outlet end intersects a centerline through the fluid inlet end at an angle greater than 5 degrees, and forming in the tip body a fluid passageway internal to the tip, has an inlet end and a subgingival outlet end, the subgingival outlet end of the tip has a longest cross-sectional dimension of less than 0.03 inch; bending the tip body in a second direction so that a centerline through the fluid outlet end intersects a centerline through the fluid inlet end at an angle of substantially 0 degrees, continuing to bend the tip body in the second direction so that the centerline through the fluid outlet end intersects the centerline through the fluid inlet end at an angle greater than 5 degrees.

Method of making a tool tip and tool tip


A phantom manufacturing method is disclosed, which comprises the steps of: disposing an exudate network with interconnecting first channel and second channel in a container in a manner that the first channel is transversely disposed for an exudate to flow laterally in the container and the top portion of the second channel is longitudinally disposed for the exudate to flow vertically in the container; forming a plurality of stacking solid layers while arranging the first channel at the bottommost solid layer and the top of the second channel at either inside the topmost solid layer or to be exposed outside the top of the topmost solid layer as the bottom of the second channel is connected to the first channel and extending therefrom upward to the topmost solid layer; and forming a recess in the topmost solid layer while connecting the bottom thereof to the second channel.

Generally, a vacuum assisted closure (VAC) therapy or a negative pressure wound therapy (NPWT), being classified as a kind of adjuvant physical therapy, is operated by applying a negative pressure pump to a patch of a bio-compatible porous wound dressing covering a wound for forming a negative pressure inside the wound, by that, as the negative pressure will cause the volume of the porous wound dressing to contract and consequently force the wound to close as well as the shear stresses of the contracted porous wound dressing will cause a drag to the boundary tissues of the wound for enhancing cell division and proliferation, the healing of the wound can be accelerated. It is noted that the application of the negative pressure through the porous wound dressing not only can improve the growth of blood vessels and the local blood circulation as the flowing of tissue fluid between cells can be enhanced, but also it can prevent the happening of edema and inflammation, create a moist healing environment with good wound protection as it can draw cellular waste and excess tissue fluid out of the wound, and thus the healing time of the wound can be reduced.
Conventionally, the development of a NPWT system must go through several clinical experiments just to verify its effectiveness in physical and biological therapy. Currently, it is common to use living animal, such as pig, rabbit or mouse, in such clinical experiments. However, not to mention the difficulties in development of a NPWT system using the result of such animal experiment as there are conceivable differences between human tissue and animal tissue, just the more and more strict animal experiment regulation by the effort of humanitarian and animal protection associations will cause huge delay in developing a mature NPWT product.
In view of the aforesaid shortcomings, there are already many phantoms that are capable of mimicking human tissue being developed for using in those therapeutic effectiveness verifications, such as solid water phantom, polystyrene phantom acrylic phantom, thermoplastic phantom and gelatin phantom, etc. The aforesaid phantoms are mostly being molded into blocks or other geometrical shapes so as to facilitate the proceeding the effectiveness verifications. It is noted that the gelatin phantom made of animal protein can be applied in applications more than those other phantoms. In food industry, it can be made into all kinds of soft sweets, mousse, jelly, meat aspic, cakes, and so on; and in pharmaceutical industry, it can be made into hard capsules, soft capsules, sugar-coated pills, and so on; and in biomedicine industry, it can be made into artificial dressings, artificial skins and phantoms, and so on. As the gelatin can form a smooth and elastic jelly that its strength is adjustable according to its gelatin concentration, and is a hydrophile jelly capable of melting into liquid-like glue when it is heated to a temperature above 40° C. and solidifying back into jelly when it is cooled down to below 30° C., phantoms of different elasticity and thicknesses can be made from gelatins of different compositions for the purpose of mimicking different layers in a human skin like epidermis layer, dermis layer, and subcutaneous layer. Moreover, the gelatin phantom can be formed with a plurality of layers, each having channels formed therein to be used for operating as the blood vessels in the skin as there can be a blood mimicking fluid flowing in those channels.
However, as the channels of different layers in the conventional gelatin phantom are not formed interconnecting with each other, the blood mimicking fluid is prohibited from flowing between layers so that even the blood mimicking fluid flowing in the channels of the topmost layer is flowing under a sculpted wound formed on the gelatin phantom and can not ooze out of the wound just likes an actual skin wound does. It is known that the human blood and tissue fluid are capable of flowing between skin layers and thus it is for sure that there will be blood and tissue fluid ooze out of an open wound at any time during the healing. Therefore, the conventional gelatin phantom can not mimic the exudate of an open wound, there will be errors when it is used for experimenting how exudates can affect the efficiency of a negative pressure wound therapy (NPWT) system.

Industrial Technology Research Institute


A method of producing a phosphor plate comprising the step of vapor depositing a phosphor raw material on a substrate to form a phosphor layer on the substrate in a vacuum container of a vapor deposition apparatus, wherein the vapor deposition is carried out in an atmosphere of a fluorinated solvent gas having a partial pressure of 5×10−4 to 5×10−1 Pa.

Hitherto, a radiation image such as an X-ray image is widely applied for diagnosing in medical field. Particularly, an intensifying screen-film radiation image forming system is still used in the medical field of the world as an image taking system having high reliance and superior cost performance as a result of improvement in sensitivity and image quality in long history of the system. Recently, a digital radiation image detecting device, typically computed radiography (CR) and a flat panel radiation detector (FPD), has been realized and it has been made possible to take a radiation image in a form of digital information and to freely treat or instantaneously transmit the information.
In the CR and FPD, a phosphor plate is provided, which emits light when that is irradiated by radiation, and the luminance of the light emitted by the phosphor plate is an important factor for obtaining a clear radiation image. The CR has a stimulable phosphor plate as the phosphor plate.
The CR has a stimulable phosphor plate as a phosphor plate. The stimulable phosphor plate is a plate which accumulates radiation permeated through a subject and emits light corresponding to the amount of accumulates radiation when the plate is irradiated by exciting light. The plate is constituted by a phosphor layer provided on a substrate. It has been known regarding the stimulable phosphor plate that columnar crystals are formed on the substrate and the luminance of the emitted light is raised when cesium bromide displaying high conversion efficiency of from radiation to light is deposited on the substrate by vapor deposition for forming the phosphor layer. Particularly, in the techniques described in Patent Document 1, it is planed to raise the luminance of the emitted light of the plate by heating the substrate on which the phosphor layer is formed for removing moisture from the crystals of the phosphor layer in addition to the vapor deposition of the cesium bromide onto the substrate.
On the other hand, the FPD has a scintillator plate as the phosphor plate. The scintillator plate is a plate which instantaneously emits light corresponding to the radiation permeated through a subject without irradiation of the exciting light. The scintillator plate is constituted by a phosphor layer provided on a substrate similarly to the above stimulable phosphor plate. As to the scintillator plate, it has been known that the luminance of emitted light is improved when the phosphor layer cesium iodide having high conversion efficiency of from radiation to stimulated light is formed vapor depositing so as to columnar crystals are formed on the substrate. Particularly, in Patent Document 2, the luminance of emitted light is increase by simultaneously spattering an activator such as indium together with the vapor deposition of cesium iodide on to the substrate.
Patent Document 1: Japanese published unexamined application (JP-A) 2003-279696, (paragraphs 0034 to 0035)
Patent Document 2: JP-A 2001-59899, (paragraph 0041)
The phosphor layer is insufficient in the light emission efficiency and space to be improved remains as to the phosphor layer even when the phosphor layer is constituted by cesium bromide or cesium bromide having high conversion efficiency of from radiation to stimulated light or the phosphor layer is improved by techniques such as those described in Patent Documents 1 and 2.
An object of the invention is to provide a producing method of phosphor plate by which the luminance of emitted light can be further improved and a phosphor plate produced by such the method.

Production method of phosphor plate and phosphor plate


[Object] To provide an information processing system and an information processing method capable of grasping propagation of acts in a society. [Solution] An information processing system including: a communication unit configured to acquire act information indicating occurrence of a first act from a first user to a second user; an accumulation unit configured to accumulate at least a user who has performed the act, a user influenced by the act, and a type of the act in units of acts in order of occurrence of the acts; and a control unit configured to, when a second act determined to have influenced the first act is found from among acts that are accumulated in the accumulation unit and from which the first user has received influence in past, perform control to record the first act and the second act in association with each other in the accumulation unit.

In recent years, research for measuring happiness of people and measures for improving happiness have been underway in units of regions, companies, countries, and the like, and policies for directing people's life to a good direction have been considered.
In addition, there have been movements for improving happiness of the entire society by encouraging acts of kindness. For example, there is a municipality that has a system of recommending a person who acted kindly and honoring the person once a year.
In regard to such evaluation of acts of kindness, for example, Patent Literature 1 below describes a gratitude providing system that provides, in the form of visual value information, the feeling of gratitude to another user who has given an impressive or kind act.
In addition, with recent development of communication technologies, technologies of grasping a communication path of the Internet or the like and an e-mail forwarding history have been proposed. For example, Patent Literature 2 below describes that an e-mail forwarding history is stored in an e-mail processing server, and when a reminder e-mail is received from a requester, the reminder e-mail is forwarded to a destination to which a request e-mail from the requester has been forwarded. In addition, Patent Literature 3 below describes a system in which a node on a forwarding path of content cashes content and saves a content forwarding history. In addition, Patent Literature 4 below describes that even if friends, attributes, or the like of users are not registered in advance, a social graph indicating connections and relationships between people can be generated. For example, the URL of a restaurant to be a dinner venue is sent to participants, and a social graph of people participating in the dinner is automatically generated on the basis of access to the URL by the participants.

Information processing system and information processing method


A method of making cellulose ester photographic film base employing microwave radiation for removing the final portion of solvent present in the film.

FIELD OF THE INVENTION
This invention relates Lo a method of making cellulose ester photographic film base and more particularly to a method of preparing photographic film base having fewer imperfections than the methods currently employed which method is conducted in a much shorter period of time.
It is known in the art to prepare cellulose ester photographic film base materials by casting a cellulose ester solution or dope in the form of a film on a highly polished surface of a rotating wheel or band, causing the film to set by evaporation of a portion of the volatile solvent present in the casting solution, stripping the film from the casting wheel or band while it still contains a high percentage of solvent but has sufficient strength to maintain its form and then drying the film by passing it through various chambers while directing hot air over the surface thereof as the film is continuously transported by numerous rollers until the final and desired state of dryness is reached. Then the film base is wound upon itself in a roll for further processing into photographic element.
A problem chat accompanies this process is that as the utility for the film base is in the production of photographic film of all types, any imperfections that are present in the film will be carried over into the final product. Thus, rigid inspection methods must be employed and any imperfections Chat are present in the film base must be removed before the base can be employed as the substrate upon which photographic elements are built. As each of the rollers over which the film base passes during the drying cycle can be a source of imperfections in the film base, it is desirable to reduce the number of such rollers to a minimum and at the same time shorten the preparation time for the cellulose ester film base.

Method of making cellulose ester photographic film base


The present invention provides an assay for the identification of agents which can modulate TOR-mediated phosphorylation of substrate proteins. The assays of the invention utilize substrate proteins whose amino acid sequence contains the Ser/Thr motif recognized by TOR. Naturally occurring TOR which may be used in the methods of the invention include TOR isolated from a variety of species, particularly mammalian tissues.

The Target of Rapamycin (TOR) is a highly conserved protein kinase found in both prokaryotes and eukaryotes. TOR proteins are members of the phosphoinositide (PI) 3-kinase related kinase (PIKK) family, which includes mammalian ATM, ATR, and DNA-PK (Tibbetts, and Abraham, Signaling Networks and Cell Cycle Control: The Molecular Basis of Cancer and Other Diseases, 5:267 (2000)). Like other PIKK family members, the TORs are large polypeptides (280–300 kDa) that bear a carboxy-terminal region with sequence similarity to the catalytic domains of PI3-kinases (PI3K) (Abraham et al., Annu. Rev. Immunol. 14: 483 (1996)). PIKK family members possessing active kinase domains phosphorylate proteins on serine or threonine residues. The consensus phosphorylation site for all PIKK family members (except the TORs) is serine/threonine followed by glutamine at the +1 position. The preferred sequence motif for the TORs remains unclear; however, known in vitro substrates contain serine/threonine followed by proline or a hydrophobic amino acid at the +1 position. The lack of a consensus motif for substrate recognition by TOR kinases hints that these PIKK family members may rely on an alternative mechanism for substrate identification or regulation in intact cells. (Abraham, Cell 111: 9 (2002)).
Several lines of evidence suggest that the TOR proteins function in a nutrient-sensing checkpoint control capacity. Both TOR and PI3K signaling are required for the activation (or inactivation) of several downstream effector proteins. However, whether TOR activity is regulated by PI3K, or whether the two signaling pathways function independently, is unknown. Overexpression of a membrane-targeted Akt/PKB protein (a downstream effector of PI3K) in mammalian cells leads only to a modest increase (or no change) in TOR kinase activity (as assayed in vitro), and moderately increases TOR autophosphorylation in vivo, as assessed with the S2481 phospho-specific antibody (Scott, et al., PNAS 95: 7772 (1998); Peterson, et al., J. Biol.Chem. 275: 7416 (2000); Sekulic, et al., Cancer Res. 60: 3504 (2000)).
Rapamycin is a bacterial macrolide with antifungal and immunosuppressant activities (Dumont et al., J. Immunol. 144: 251 (1990)). For example, rapamycin forms a complex with the immunophillin FKBP12 which then inhibits the kinase activity of TOR (Brown et al., Nature 369: 756 (1994); Kunz et al., Cell 73: 585 (1993)). Rapamycin treatment of cells leads to the dephosphorylation and inactivation of the cell-growth-promoting P70 S6 Kinase (Jeffries et al., EMBO J. 15: 3693 (1997); Beretta et al., EMBO J. 15: 658 (1996); Raught et al, PNAS 98: 7037 (2001)). In addition to rapamycin, wortmannin and LY294002 have also been shown to affect TOR signaling. Wortmannin is an active site inhibitor that abolishes TOR autophosphorylation. LY294002 blocks PI3K dependant Akt phosphorylation and kinase activity and inhibits TOR autophosphorylation as well. (Brunn et al, EMBO J. 15: 5256 (1996)). Rapamycin, wortmannin and LY294002 are commercially available from Cell Signaling Technology, Beverly, Mass., as Cat. Nos. 9904, 9951 and 9901, respectively.
Inactivation of the TOR proteins, or rapamycin treatment, mimics nutrient deprivation in yeast, Drosophila, and mammalian cells (Zhang, et al, Genes Dev. 14: 2712 (2000); Sekulic, et al., Cancer Res. 60: 3504 (2000); Navé, et al., Biochem. J. 344: 427 (1999); Barbet, et al, Mol. Biol. Cell 7: 25 (1996)). Thus, a current working model for TOR signaling proposes that these kinases relay a permissive signal to downstream targets only in the presence of sufficient nutrients to fuel protein synthesis. Because the TOR proteins appear to function in a coregulatory capacity with other conventional, linear signaling pathways, a passive nutrient sufficiency signal may be combined with stimulatory signaling from a second pathway to coordinate cellular processes that require the uptake of nutrients. The absence of either signal is predicted to prohibit activation of downstream targets. (Raught, et al,. PNAS 98: 7037 (2001)).
It is believed that TOR signaling is affected through a combination of repression of phosphatase activity, and direct phosphorylation of downstream targets. Genetic screening in Saccharomyces cerevisiae has identified a phosphatase-associated protein (Tap42p), as one component of a rapamycin-sensitive signaling pathway (Schmelzle, et al., Cell 103: 253 (2000); Di Como, et al., Genes Dev. 10: 1904 (1996)). Tap42p phosphorylation is modulated by TOR signaling, which in turn regulates Tap42p interaction with phosphatases, such as PP2A (Jiang, et al., EMBO J. 18: 2782 (1999); Schmidt, et al., EMBO J. 17: 6924 (1998); Beck, etal., Nature (London) 402: 689 (1999); Di Como, et al., Genes Dev. 10: 1904 (1996); Jiang, et al., EMBO J. 18: 2782 (1999)). Tap42 orthologs are found in Arabidopsis (Harris, et al., Plant Physiol. 121: 609 (1999)), Drosophila, (GenBank accession number AAF53289), and mammalian cells (Inui, et al., J. Immunol. 154: 2714 (1995); Onda, et al., Genomics 46: 373 (1997)). In mammals, the B cell receptor binding protein α4 (a.k.a Ig binding protein 1, IGBP1) is the ortholog of Tap42p (Inui, et al., J. Immunol. 154: 2714 (1995); Onda, et al., Genomics 46: 373 (1997)).
TOR acts directly on other downstream targets, regulating the balance between protein synthesis and protein degradation in response to nutrient quality and quantity. TOR proteins regulate: (i) initiation and elongation phases of translation; (ii) ribosome biosynthesis; (iii) amino acid import; (iv) the transcription of numerous enzymes involved in multiple metabolic pathways; (v) autophagy, and (vi) expression of hypoxia-induced factor (HIF)-1 in oxygen-deprived cells (for a review see; Raught, et al., PNAS 98: 7037 (2001); see also, Hudson et al., Mol. Cell Bio.l 22: 7004 (2002)).
TOR signaling, in combination with the PI3K pathway, initiates the translation of rapamycin-sensitive mRNAs. In the presence of sufficient nutrients to fuel protein synthesis, TOR and PI3K signaling activate the S6Ks, and one or more unknown kinases, to effect phosphorylation of the ribosomal S6 protein, eIF4B, eIF4GI, and the 4E-BPs. TOR signaling has been reported to inhibit eEF2 phosphorylation (possibly via inhibition of the eEF2 kinase), thus, increasing elongation rates (Raught, et al., PNAS 98: 7037 (2001)).
Inhibition of TOR activity in S. cerevisiae potently represses translation initiation, concomitant with polysome disaggregation and cell cycle arrest in G.sub. 1 (Barbet, et al., Mol. Biol. Cell 7: 25 (1996)). The mechanism for this translational repression is not understood, but could be due, at least in some strains, to the degradation of the initiation factor eIF4G (Berset, et al., Proc. Natl. Acad. Sci. USA 95: 4264 (1998); Powers, et al., Mol. Biol. Cell 10: 987 (1999)).
In addition to its effect on the phosphorylation state of proteins involved in translational control, TOR signaling regulates an abundance of the components of the translation machinery, at both the transcriptional and translational levels. Through the S6Ks, TOR signaling regulates the translation of ribosomal protein mRNAs in mammalian cells (Leicht, et al., Cell Growth Differ. 7: 1199 (1996); Mahajan, Int. J. Immunopharmacol. 16: 711 (1994)). Transfer of cultured mammalian cells from standard growth medium into amino acid and/or glucose-free medium leads to rapid dephosphorylation of two TOR substrates, S6K1 (p70 S6 kinase) and 4EBP1 (PHAS-I) (Gingras et al., Genes Dev. 15: 807 (2001)). In the dephosphorylated state, S6K1 activity is repressed in starved cells, and nutrient stimulation leads to its phosphorylation and activation.
Activated S6K1 stimulates ribosome biogenesis, upregulating the translational capacity of the cell. Similarly, 4E-BP1 binds avidly to eIF-4E, thereby suppressing cap-dependent protein synthesis. Restoration of nutrients provokes multisite phosphorylation of 4E-BP1 by TOR (and possibly other protein kinases), release of eIF-4E, and resumption of cap-dependent translation. Activators of TOR could also be useful in the therapy of muscle degeneration induced by diseases such as cancer or muscular dystrophy (for review, see Glass, Nature Cell Biol. 5(2):87 (2003)). Thus TOR is a central component of a rapamycin-sensitive signaling pathway that coordinates protein synthesis with glucose and amino acid availability. (Abraham, Cell 111: 9 (2002)).
In both yeast and mammalian cells, TOR signaling regulates autophagy. When nutrient levels are low, eukaryotic cells degrade cytoplasmic proteins and organelles to scavenge amino acids, in a process termed autophagy (Klionsky, et al., Science 290: 1717 (2000); Kim, et al., Annu. Rev. Biochem. 69: 303 (2000); Klionsky, et al., Annu. Rev. Cell Dev. Biol. 15: 1 (1999)). Switching yeast cells to a poor carbon or nitrogen source induces a state of quiescence (G.sub.0). Similarly, rapamycin addition to yeast cultures or to mammalian cells in culture induces autophagy, even in a nutrient-rich medium (Noda, et al., J. Biol. Chem. 273: 3963 (1998); Blommaart, et al., J. Biol Chem. 270: 2320 (1995)). TOR signaling modulates gene expression via cytoplasmic sequestration of several nutrient-responsive transcription factors. TOR signals to several specific effectors (Tap42, Mks1p, Ure2p, Gln3p, and Gat1p) eliciting changes in the expression levels of enzymes involved in several different metabolic pathways (Shamji, et al., Curr. Biol. 10: 1574 (2000); Chan, et al., PNAS USA 97: 13227 (2000)). How TOR signaling may affect the transcription rates of metabolic enzymes in multicellular organisms has not yet been elucidated (Blommaart, et al., J. Biol. Chem. 270: 2320 (1995); Shigemitsu, et al., J. Biol. Chem. 274: 1058 (1999)).
In mammalian cells, autophagy is inhibited by amino acids and insulin. Activation of S6K is associated with inhibition of autophagy in rat hepatocytes, and the inhibition of autophagy by amino acids could be partially prevented by rapamycin treatment (Blommaart, et al., J. Biol. Chem. 270: 2320 (1995); Shigemitsu, et al., J. Biol. Chem. 274: 1058 (1999)).
The observation that rapamycin can inhibit long-term facilitation in Aplysia neurons has implicated TOR signaling in the control of neuronal protein synthesis (Casadio, et al., Cell 99: 221 (1999)). Several types of neurotransmitters were described to affect the activity of the rapamycin-sensitive pathway leading to S6K1 and 4E-BP1 phosphorylation. Serotonin (5-HT) addition to Aplysia neurons or Chinese hamster ovary (CHO) cells expressing the 5-HT1B receptor increases phosphorylation of S6K1 in a rapamycin-dependent manner (Khan, et al., Neurosci. 21: 382 (2001); Pullarkat, et al., J. Neurochem. 71: 1059 (1998)). Dopamine addition to CHO cells also activates S6K1 in a rapamycin-dependent manner (Welsh, et al., J. Neurochem. 70: 2139 (1998)). Finally, both S6K1 and 4E-BP1 phosphorylation is induced by stimulation of the μ-opioid receptors (which mediate the analgesic and addictive properties of morphine) by the agonist [D-Ala2,N-MePhe4,Gly5-ol]enkephalin (DAMGO; Polakiewicz, et al., J. Biol. Chem. 273: 23534 (1998)). TOR interacts with gephyrin, a tubulin-binding protein involved in neuronal γ-aminobutyric acid type A (GABAA) and glycine receptor clustering (Sabatini, et al., Science 284: 1161 (1999); Scheper, et al., J. Biol. Chem. 267: 7269 (1992); Essrich, et al., Nat. Neurosci. 1: 563 (1998); Kirsch, et al., Nature (London) 366: 745(1993)). Gephyrin binding is reportedly required for signaling to S6K1 and 4E-BP1, and, consistent with a role in localized protein synthesis, a fractionation experiment demonstrated that TOR and gephyrin were enriched in the synaptosomal fraction but not in the post synaptosomal fraction (Sabatini, et al., Science 284: 1161 (1999)).
The role of TOR in the numerous signaling pathways listed above, as well as others, makes modulating TOR activity a potentially desirable treatment method for a variety of conditions. For example, TOR kinase activity is important for antigen-activated T-cell proliferation, thus, rapamycin, which inhibits TOR activity, is useful as an immunosuppressant. (Abraham et al., Annu. Rev. Immuno. 14: 483 (1996); Morice et al., J. Biol Chem 268: 3734 (1993)). Similarly, TOR has been identified as a therapeutic target involved in human cancers (Huang et al., Current Opinion in Investigational Drugs. 3(2):295 (2002)). However, there is a need in the art to fully understand the role of TOR in many signaling pathways, and to identify the various modulators of TOR kinase activity within these pathways. Such modulators, once identified, may be useful in treating many of the disorders associated with TOR signaling pathways.
A few TOR modulators, such as rapamycin, wortmannin and LY29004 have already been identified; however, the discovery of additional modulating agents is necessary to address the numerous conditions affected by TOR. However, current assays for screening for such agents rely on recombinant TOR, and produce, at best, poor results. For example, in mammalian cell lines, recombinant TOR yields are too low to be useful in any assay. Similarly, in bacterial cell lines, recombinant TOR is expressed in an insoluble form, and thus cannot be used in an assay. In addition, recombinant TOR, when expressed in insect cell lines, has no detectible kinase activity, and thus is not useful in any assays. Such limitations serve as a barrier to elucidating TOR's role in many signaling pathways and in identifying TOR modulators, which may be useful in treating the many disorders associated with TOR signaling. Thus, because of the limitations of recombinant TOR, there are no useful assays in the current art employing recombinant TOR. This is particularly true for high throughput screening assays, which are even less tolerant of recombinant TOR's limitations. Accordingly, there is a need in the current art for a TOR assay that measures TOR kinase activity, and that is adaptable to high throughput screening.

Screening assay for agents that alter target of Rapamycin activity

The Burnham Institute for Medical Research


A storage system comprises a storage drive that has a physical connector A and a physical connector B for connecting to the first control device and second control device, respectively. The physical connector A and physical connector B are independent access ports. The first control device is configured to access the storage drive through the physical connector A, and the second control device is configured to access the storage drive through the physical connector B.

With development of technologies such as a big data analysis technology and an internet of things technology, data has become a core element for promoting progress of a related technology. Therefore, it becomes more important to ensure data storage reliability.
A data storage system includes a drive controller and a drive. Storage architectures of the storage system are classified into a centralized storage architecture and a distributed storage architecture based on a manner in which the drive controller accesses the drive. In the prior art, both the centralized storage architecture and the distributed storage architecture are inherent designs. To be specific, regardless of a storage architecture in the two storage architectures, the drive controller and the drive are fixedly connected and cannot be separated. If one storage architecture needs to be switched to the other storage architecture, for example, if the centralized storage architecture is to be switched to the distributed storage architecture, an entire storage architecture needs to be purchased. To be specific, a drive controller and a corresponding drive of the distributed storage architecture that are integrated need to be purchased. Apparently, costs are relatively high. It can be learned that a storage architecture in the prior art is not flexible, and is inconvenient for flexible deployment.

This patent is subject to a terminal disclaimer.

Storage system and method for switching working mode of storage system