An automatic meter reading system that includes a head end controller and an endpoint that is interfaced to a utility meter. The head end controller and the endpoint communicate via RF communication. The endpoint includes an internal clock that synchronizes itself to a clock countdown signal. The clock countdown signal is generated by the head end controller through use of sequence inversion keying.

Wireless automatic meter reading systems are well known. Typically, each utility meter is provided with some type of encoder/receiver/transmitter endpoint, such as the Itron, Inc. ERT. In the instance of gas and water meters, that endpoint is likely battery-powered. The endpoint collects the meter readings and periodically transmits those readings over a network to a central station. The power limitations imposed by the need for the endpoint to be battery powered and by regulations governing radio transmissions often prevent direct radio transmissions to the central station. Instead, wireless meter reading systems utilize a layered network of overlapping intermediate receiving stations that receive transmissions from a group of meter encoders and forward those messages on to the next higher layer in the network as described, for example, in U.S. Pat. No. 5,056,107, which is hereby incorporated by reference. These types of layered wireless transmission networks allow for the use of lower power, unlicensed wireless transmitters in the thousands of endpoints that must be deployed as part of a utility meter reading system for a large metropolitan area.
In 1985, as an attempt to stimulate the production and use of wireless network products, the FCC modified Part 15 of the Radio Spectrum Regulation, which governs unlicensed devices. The modification authorized wireless network products to operate in the industrial, scientific, and medical (ISM) bands using spread spectrum modulation. The ISM frequencies that may be used include 902 to 928 MHz, 2.4 to 2.4835 GHz, and 5.725 to 5.850 GHz. The FCC allows users to operate spread spectrum wireless products, such as utility metering systems, without obtaining FCC licenses if the products meet certain requirements. This deregulation of the frequency spectrum eliminates the need for the user organizations to perform costly and time-consuming frequency planning to coordinate radio installations that will avoid interference with existing radio systems.
Currently, synchronization between a transmitter and a receiver is accomplished by using a synchronization pulse, which may interfere with hardware clock recovery, or by using Barker coding type approaches, which require receivers to stay on at length. However, these current synchronization techniques do not prevent collisions in endbound data packets as the endpoints are not time synchronized between the transmitter and receiver. This lack of endpoint synchronization further results in limitations on individual cell capacities as well as inherent difficulties in implementing message integration techniques.
Accordingly, there is a need for a battery efficient system for time synchronizing messages between transmitter and receiver that not only increases individual cell capacities but also allows for the implementation of two-way message integration techniques.

Sequence inversion keyed countdown timer utilized within a utility meter system


The present invention provides proteins having the Na+/glucose transporter activity, DNAs encoding the proteins, a method of screening for a compound enhancing or inhibiting the activity of the proteins, and compounds obtained by the screening method. The proteins having the same or substantially the same amino acid sequence as the amino acid sequence represented by SEQ ID NO: 1, 15 or 26 are useful as a diagnostic marker for a disease such as diabetes. The compounds enhancing or inhibiting the activity of the proteins, obtained the screening method using the proteins, can be used as a prophylactic and/or therapeutic agent for a disease such as diabetes and hyperlipidemia.

A membrane protein called glucose transporter is required on the cell membrane to move glucose across the cell membrane from the outside into the inside, and vice versa.
The glucose transporter is divided into two major classes; one is a passive transporter or the facilitated diffusion-type glucose transporter (GLUT), and the other is an active transporter or the Na+/glucose transporter (SGLT), which transports glucose against its concentration gradient through the coupling with Na+ ion transport. There are 8 GLUT isoforms, which have a common structure having a molecular weight of about 50000 and 12 transmembrane spans.
SGLTs have a common structure having a molecular weight of about 75000 and 14 transmembrane spans.
The functions and expression sites of SGLTs 1 and 2 are outlined in Nippon Rinsho (Japanese Clinical) 55, extra number, Diabetes I, p. 59-64, 1997.
The human SGLT1 is expressed specifically in small intestine and kidney, and has a high affinity to glucose and a low transport activity, while the human SGLT2 is expressed specifically in kidney, and has a low affinity to glucose and a high transport activity. SGLTs have functions of absorbing glucose in small intestine and reabsorbing glucose in kidney, which has been excreted into the urine.
It is shown in a diabetes model rat that in consequence of inhibiting glucose reabsorption in kidney by inhibiting SGLT, glucose is excreted in the urine to decrease the blood glucose level (Diabetes 48: 1794-1800, 1999).
Until now, it has been considered that the passive transporter GLUT2 is primarily expressed in pancreatic beta cells and liver cells. GLUT2 is characterized by a low affinity to glucose and a high maximal transport activity. In pancreatic beta cells, GLUT2 is considered to take in glucose in a blood glucose level-dependent manner and function as glucose sensor along with glucokinase for the glucose level-dependent insulin secretion. In liver cells, GLUT2 is considered to function as glucose transporter to take blood glucose into the cells against the glucose concentration gradient across the cell membrane at high blood glucose level after a meal, and to release glucose into the bloodstream, which is produced intracelluarly through glycogenolysis or gluconeogenesis on an empty stomach.
It is reported that in samll intestine cells, human SGLT1 is moved from the cytoplasma to the cell membrane through the action of gastrointestinal hormone GLP-2, resulting in 3-fold increase in the glucose uptake activity (Am. J. Phsiol. 273, R1965-R1971, 1997).
The currently used insulin secretagogue (SU) closes KATP-channel in pancreatic beta cells to force the cells to secrete insulin irrespective of the blood glucose level. Accordingly, it is difficult to control the blood glucose level with SU, bringing about side effects, such as hypoglycemia, obesity through excessive insulin secretion. A phenomenon called secondary SU failure occurs, in which SU become ineffective after 10-year administration on average. This failure is considered due to fatigue of the pancreatic beta cells.
Therefore, it can be expected that activation of SGLT homolog function may enhance glucose uptake into pancreatic beta cells, and then the blood glucose-dependent insulin secretion. In addition, an activator of SGLT function is expected to cause no side effects, which the currently used insulin secretagogue (SU) shows.
In liver cells, GLUT2 releases glucose from liver into the bloodstream on an empty stomach, but a SGLT homolog is considered to enhance glucose uptake from blood into liver in spite of glucose concentration gradient across the cell membrane. Therefore, it can be expected to prevent glucose release from liver into blood, and thus a high blood glucose level on an empty stomach in a diabetes patient without occurrence of side effects such as hypoglycemia
Furthermore, an inhibitor of SGLT is capable of lowering blood glucose level by inhibiting glucose reabsorption in kidney, and thus is expected to prevent fat synthesis by reducing glucose uptake into liver.

Proteins having glucose transporter activity


A method is provided that allows simultaneous control of macroscopic azimuthal and zenithal liquid crystal alignment (φ, θ) across a liquid crystal layer by controlling the area ratios between first, second and third different types of alignment region (T1, T2, T3) in a patterned alignment layer, the three different types of alignment region (T1, T2, T3) tending to induce liquid crystal alignment in the liquid crystal layer in three different respective, non-coplanar, principal orientations (z, x, y). In the illustrated example, the first type of alignment region (T1) tends to induce substantially homeotropic alignment (in the z direction) and the second and third types of alignment region (T2, T3) tend to induce substantially planar alignment in different, orthogonal, principal orientations (in the x and y directions). Control of macroscopic zenithal liquid crystal alignment (θ) is achieved by controlling the area ratios between the homeotropic (T1) and planar region types (T2, T3), and control of macroscopic azimuthal liquid crystal alignment (φ) is achieved by controlling the area ratio between the two planar region types (T2, T3).

1. Field of the Invention
The present invention relates to the control of macroscopic liquid crystal alignment in a liquid crystal layer, and to an optical device comprising a liquid crystal layer having its macroscopic liquid crystal alignment controlled in this way.
2. Description of the Related Art
FIG. 1 of the accompanying drawings illustrates the co-ordinate system of a LC director (average molecular orientation) in space. The angle θ is the zenithal (out of plane) angle while φ is the azimuthal (in-plane or planar) angle. The angle θ is also known as the tilt angle while φ is also known as the twist angle. The LC layer (or substrate) is in the x-y plane.
Patterning of liquid crystal alignment on a gross scale is known. In this context, gross patterning refers to alignment regions that have a lateral extension larger than the thickness of the liquid crystal layer. The resulting liquid crystal layer has at least two domains that are optically distinct with the patterning in one region having negligible effect on the patterning of a neighbouring region.
Patterning of alignment on a fine scale (˜1 μm) in liquid crystal devices has also been disclosed previously. "Surface alignment bistability of nematic liquid crystals by orientationally frustrated surface patterns" Kim et al, Applied Physics Letters, 78, pp3055 (2001) describes azimuthal micropatterning in two directions and demonstrates bi-stable bulk director orientations. "Tristable nematic liquid crystal device using micropatterned surface alignment" Kim et al, Nature 429, pp159 (2002) describes azimuthal micropatterning in three directions and demonstrates tri-stable bulk director orientations. Kim et al do not disclose spatially varying the proportions of the patterned alignment regions or mention possible devices that could result from such patterning. The azimuthal patterning in both these papers is achieved using an atomic force microscope (AFM) to rub the substrate and achieve domains that have a width of 4 μm (down to 0.5 μm). However, it takes between 2 and 10 hours to rub an area the size of a single pixel (90 μm×90 μm) using an atomic force microscope (AFM). Consequently, AFM rubbing is not considered to be a production-viable technique
"Alignment of nematic liquid crystals by inhomogeneous surfaces" Ong et al, Journal of Applied Physics, 57, pp186 (1985) describes the use of a surface composed of patches that favour homeotropic alignment that are surrounded in a matrix favouring planar alignment. The resulting zenithally patterned surface produces a bulk pretilt that is between planar and homeotropic. The pretilt is a function of the area ratio between the homeotropic and planar alignment regions. However, this zenithal patterning method relies on SiO and metal film deposition, and SiO deposition is not considered a production-compatible technique. The fabrication method described by Ong et al could not be used to spatially vary the proportions of the homeotropic and planar alignment directions. Therefore the average bulk zenithal angle will be the same everywhere (i.e. no spatial variation of zenithal retardation is possible). Ong et al do not disclose spatially varying the proportions of the patterned alignment regions or mention possible devices that could result from such patterning.
Zenithally bistable displays (ZBD) have been disclosed in several patents, for example in WO 97/14990. All ZBD devices have a locally uniform surface pretilt on a grating structure The resulting bulk optical properties of the ZBD are a consequence of the topology of the undulating surface.
The techniques mentioned above are considered either to rely on commercially incompatible production methods or to have insufficient patterning flexibility to enable a number of novel optical elements to be made, or both.

Control of liquid crystal alignment in an optical device


A technique for generating analog waveforms includes combining a desired, in-band signal with a randomizing, out-of-band signal at an input of a DAC, operating the DAC to generate DAC output based on a combination of the desired signal and the randomizing signal, and filtering the DAC output to pass the desired signal while removing the randomizing signal.

Direct-digital synthesizers (DDSs) find common usage in many areas of technology that require the generation of analog waveforms. These areas include, for example, telecommunications, simulations, audio/video equipment, and electronic test equipment. A central component of a DDS is a DAC (digital-to-analog converter), i.e., a device that converts digital inputs (numbers) to analog outputs (voltages or currents). In a common arrangement, the DAC is fed a sequence of digital input values that describe successive levels of a desired waveform, such as a sine wave or any other periodic waveform. For each digital input value, the DAC generates a corresponding analog output whose voltage or current is proportional to the numerical value of the input. Each output from the DAC appears as a single voltage or current level, but the sequence of outputs describes the desired waveform. Typically, a low-pass or band-pass filter is applied to the output of the DAC to smooth transitions between discrete levels and to render the output as a continuous signal.
Some applications place high demands on DDSs in terms of the spectral purity of their output signals. For example, a DDS programmed to generate a sine wave should ideally produce a single tone, at the sine wave's frequency, but should produce little or no output at other tones. There should ideally be minimal harmonics, noise, or spurs. As is known, "spurs" are erroneous tones whose magnitude (size) is well above a usual noise floor of the DDS output. Spurs can interfere with the proper functioning of equipment, which may malfunction or perform poorly in their presence. Minimization of spurs is thus a critical aspect of DDS design.

Suppressing spurious signals in direct-digital synthesizers


An image forming apparatus of this invention includes abbreviated keys that realize abbreviated input of a transmission destination, an openable cover provided so as to cover the abbreviated keys, and first and second cover open/closed detection switches configured to output an open state and a closed state of the cover. When an operation of an abbreviated key is received, if the first and second cover open/closed detection switches indicate different detection results, mismatch information indicating that different output has been occurred from the first and second cover open/closed detection switches is stored in a non-volatile storage unit, and the image forming apparatus is restarted.

Field of the Invention
The present invention relates to an image forming apparatus, a control method for the same, and a storage medium.
Description of the Related Art
In recent years, the field of image forming apparatuses with a small apparatus size has not only seen fierce cost competition, but also demand for further reduction in size and increase in functionality. Also, personal computers and networks have become widely prevalent, and it has become possible to provide functionality in which an image forming apparatus and an external apparatus work in cooperation such that an image read by the scanner of the image forming apparatus can not only be transmitted as a fax, but also transmitted to an external apparatus as electronic data.
Known methods of easily designating the transmission destination when performing transmission include a one-touch key method in which transmission destinations are assigned to specific hardware keys, and an abbreviated dial method in which transmission destinations are assigned to specific digit numbers. Japanese Patent Laid-Open No. 2001-238013 proposes an image forming apparatus configured such that an openable cover is attached to the operation panel, and the functions of the one-touch keys are switched in accordance with the open/closed state of the cover.
In image forming apparatuses having hardware keys provided with this type of openable cover, consideration has been given to a technique for preventing mistaken fax transmission by providing a configuration for detecting a cover open/closed sensor abnormality. For example, some image forming apparatus have a configuration in which multiple sensors for detecting opening/closing of the cover are provided, and a one-touch key operation for a fax transmission destination is accepted only if the output from the sensors is in a predetermined combination. Japanese Patent Laid-Open No. 2008-048208 proposes a technique in which, if the output from the cover open/closed sensors is in an inappropriate combination when a one-touch key is operated, a service error is generated, and use of the apparatus is disabled.
Japanese Patent Laid-Open No. 06-303301 proposes a technique that in addition to preventing mistaken transmission by making a determination regarding the cover sensor values, also prevents mistaken transmission due to the mistaken pressing of a one-touch key or an abbreviated dial number. Specifically, a method has been proposed in which a display unit is provided for displaying the transmission destinations assigned to the one-touch keys. Furthermore, a technique has been proposed in which the user can switch the setting of whether or not registered information and a prompt for user confirmation are to be displayed before performing transmission. In this technique, "Do not display" is set as the default in consideration of user convenience in one-touch/abbreviated dialing.
However, the above-described conventional techniques have problems such as those described below. For example, with an image forming apparatus according to the above conventional techniques, if the output from the cover open/closed sensor is not appropriate, a service call is made immediately, which is not convenient for the user. However, if the service error is simply eliminated, even in the case where multiple cover open/closed sensors are provided, if there is trouble with both of the sensors, the sensor values will be the same, and it will not be possible to make a determination that the state is normal. In this case, if the setting "Display" has not been made for the input designation confirmation screen for preventing mistaken one-touch input, there is no way to allow the user to check whether or not the designated transmission destination is correct. For this reason, even if the designated transmission destination is incorrect, it is possible for transmission to be performed without the user realizing the mistake, and concern regarding mistaken fax transmission cannot be dispelled. Furthermore, envisioning the case where there is trouble with the cover sensors, if the default setting for the input destination confirmation screen is "Display", the input destination confirmation screen will be displayed even if no problem exists, thus leading to decreased usability.

Image forming apparatus, control method for the same and storage medium


Searching electronic program guide (EPG) data is described. The EPG data may be compartmentalized into channel metadata that describes characteristics of one or more channels and content metadata that describes characteristics of one or more content items. In a implementation, a method includes searching channel metadata and content metadata. A result of the searching is formed for output in conjunction with an electronic program guide (EPG).

Users have access to an ever increasing variety of content that may be output in a wide variety of ways. For example, a user may view traditional television programming received over a network by using a client, such as a set-top box. The user may also view pay-per-view movies, order video-on-demand (VOD) content, interact with a video game, play music, and so on. The user may also access content locally on the client, such as from a digital video disc (DVD), broadcast content stored on a hard disk drive for viewing in the future (e.g., a digital video recorder), and so on.
To navigate through this even increasing variety of content, the user may interact with user interface which displays representations of the content, such as an electronic program guide (EPG). For example, the EPG may enable the user to observe a listing of television programs that are currently being streamed, as well as a listing of television programs that will be streamed in the future. Additionally, the EPG may allow the user to navigate to a television program from the EPG itself. For instance, the user may select a representation of a television program to cause the client to tune to that television program.
Traditionally, an EPG is configured to locate particular content items of interest, such as a particular television program. However, content may also be known by the name of the provider instead of by the name of the content itself. For instance, a user may want to watch the "Weather Channel" and not know the name of any particular content item that is available via the Weather Channel. A traditional EPG, however, does not address the channels themselves and rather is focused on the content items that are available via the channels.
Therefore, there is a continuing need for searching of electronic program guide (EPG) data that addresses channels and channel characteristics.


A radiographic imaging control apparatus includes an input unit configured to input a radiographic image from a sensor that detects radiant ray, and a control unit configured to cause a radiant ray generation apparatus to decrease the flux of radiant ray from a predetermined maximum value to a predetermined minimum value as time passes when the radiant ray generation apparatus irradiates the sensor with radiant ray.

1. Field of the Invention
The present invention relates to a radiographic imaging control apparatus for controlling a radiant ray generation apparatus configured to irradiate a subject with radiant rays.
2. Description of the Related Art
A conventional radiographic imaging system can detect a transmission distribution of radiant rays (represented by X-rays) having been transmitted through a subject, and can be used in a medical field to help diagnose by imaging the inside of a human body.
As discussed in Japanese Patent Application Laid-Open No. 2005-124975, a conventional radiographic imaging system can realize real-time suppression of radiation exposure by changing the level of X-ray dose according to a portion of a human body to be diagnosed.
Furthermore, as discussed in Japanese Patent Application Laid-Open No. 2004-77709, the dose of X-rays used in the diagnosis of a human body can be changed according to a status of a display unit that displays radiographic image information.
However, in the imaging of a human body based on transmission of X-ray, it is inevitable that the human body is significantly exposed to the X-ray. In general, detailed diagnosis of a human body requires a higher level of X-rays and increases the risk of damaging the human body with the X-rays. On the other hand, if the level of X-ray dose is lowered for the purpose of suppressing radiation damage, the image quality of a radiographic image deteriorates due to generation and increase of noise. Thus, the X-ray procedure can cause a problem for medical purposes.
The above-described conventional system is configured to control the X-ray dose to an appropriate level according to the purpose of a radiographic imaging operation. However, according to the above-described conventional system, the X-ray dose is fixed to a predetermined level in an initial state and, after the system starts a radiographic imaging operation, an operator is allowed to manually change the X-ray dose. Therefore, the subject may be unwittingly exposed to a higher level of X-ray for a long time.
Conventional radiographic imaging systems cannot prevent the image quality of a radiographic image from deteriorating without excessively irradiating the subject.

Radiographic imaging control apparatus and method for controlling the same


An example operation may include one or more of acquiring, by a promotion processor node, consumer exploration of a product data from a blockchain, determining, by the promotion processor node, features of the product, receiving, by the promotion processor node, a promotion plan from at least one product retailer node, and executing a smart contract to generate a plurality of promotion tokens based on the features of the product and the promotion plan.

A centralized database stores and maintains data in a single database (e.g., a database server) at one location. This location is often a central computer, for example, a desktop central processing unit (CPU), a server CPU, or a mainframe computer. Information stored on a centralized database is typically accessible from multiple different points. Multiple users or client workstations can work simultaneously on the centralized database, for example, based on a client/server configuration. A centralized database is easy to manage, maintain, and control, especially for purposes of security because of its single location. Within a centralized database, data redundancy is minimized as a single storing place of all data also implies that a given set of data only has one primary record.
However, a centralized database suffers from significant drawbacks. For example, a centralized database has a single point of failure. In particular, if there are no fault-tolerance considerations and a failure occurs (for example, a hardware, firmware, and/or a software failure), all data within the database is lost and work of all users is interrupted. In addition, centralized databases are highly dependent on network connectivity. As a result, the slower the connection, the amount of time needed for each database access is increased. Another drawback is the occurrence of bottlenecks when a centralized database experiences high traffic due to a single location. Furthermore, a centralized database provides limited access to data because only one copy of the data is maintained by the database. As a result, multiple devices cannot access the same piece of data at the same time without creating significant problems or risk overwriting stored data. Furthermore, because a database storage system has minimal to no data redundancy, data that is unexpectedly lost is very difficult to retrieve other than through manual operation from back-up storage.
A trade promotion focuses on increasing the demand for products through marketing activities coordinated by manufacturers and retailers. These activities include discounts, bonus points, coupons, display fixtures, etc. However, a success rate of the trade promotions is often less 30-40% which may be attributed to the following:                The promotion activities that stem from the partnership between manufacturers and retailer tend to focus on moving merchandise, and the promotion activities fail if there is a mismatch in the consumer buying patterns;        On the other hand, consumer buying pattern-based promotion activities, such as coupons delivered at a point of sale, tend to depend on billed items that are often never used;        Due to the complexity involved in sharing the benefits back to the manufacturers, many irregularities prop up during the settlement process and eventually the promotion turns out to be beneficial only to manufacturers with a high trade volume.
Accordingly, a consumer-centric automated trade promotion based on product exploration data in blockchain networks is desired.

INTERNATIONAL BUSINESS MACHINES CORPORATION


A developing unit develops a latent image on an image carrier with toner. A toner cartridge is detachably arranged in parallel with the developing unit, and supplies the toner to the developing unit. An opening is disposed between the developing unit and the toner cartridge, through which the toner passes. The toner cartridge includes a space forming unit that forms a space in the toner stored in the toner cartridge. The space allows the toner to flow into from the developing unit.

Office automation is becoming increasingly prevalent, and use of color documents is growing. In the past, office equipment was mainly used for taking copies of documents consisting only of text. Now, documents including graphics such as graphs are prepared in personal computers, printed out from printers, and large amounts of copies are taken to produce presentation materials, for example. Images output from printers include solid images, line images, and halftone images. Thus, demands for image quality are changing, and high reliability is increasingly demanded.
Electrophotographic methods such as electrostatic recording and electrostatic printing include a developing process for developing an electrostatic image on an image carrier such as a photoconductor by applying a developer to the photoconductor, a transfer process for transferring the developed image from the photoconductor to a transfer medium such as paper, and a fixing process for fixing the image onto the paper. There are two types of developers for developing the electrostatic image formed on the photoconductor, i.e., a two-component developer including carriers and toner, and a single-component developer, which does not require carriers, including only magnetic toner or nonmagnetic toner. The two-component developer has the following disadvantages: the developer deteriorates as toner particles stick to the surfaces of the carriers; and a mixture of the toner and the carriers needs to be maintained at a certain ration, so that toner density in the developer does not decrease as the toner is consumed. Accordingly, a large-sized developing device is needed to realize such a configuration. On the other hand, the single-component developer is advantageous in that the developing device can be made compact, and that the developer can be used under any temperature or humidity conditions. Accordingly, the single-component developer is becoming a mainstream.
There are two types of single-component developers, i.e., a magnetic single-component developer including magnetic toner, and a nonmagnetic single-component developer including nonmagnetic toner. In a magnetic single-component developing method employing the magnetic single-component developer, a developing sleeve with a magnetic field generator such as a magnet provided inside holds the magnetic toner including magnetic substances such as magnetite, and a layer thickness restricting member reduces the thickness of the toner for the developing process. The magnetic single-component developer is widely used in compact printers. In a nonmagnetic single-component developing method employing the nonmagnetic single-component developer, the toner does not have a magnetic force, and therefore, a toner supplying roller is pressed against a developing sleeve to supply the toner to the developing sleeve, and the developing sleeve holds the toner by static electricity. A layer thickness restricting member reduces the thickness of the toner for the developing process. Because the toner does not include chromatic magnetic substances, the nonmagnetic single-component developer is useful for producing color images, and because the developing sleeve does not include a magnet, a light-weight, low-cost developing device can be realized. Accordingly, the nonmagnetic single-component developer is widely used in compact, full-color printers.
However, the single-component developing method has many problems to be solved. In the two-component developing method, the carriers are used to electrically charge and convey the toner. The toner and the carriers are sufficiently mixed and stirred together, and then conveyed to the developing sleeve for the developing process. Therefore, the two-component developer can be steadily charged and conveyed over a long time, and can be used in a high-speed developing device. On the other hand, the single-component developing method does not employ carriers that can steadily charge and convey the toner, and therefore, failures occur in the charging and conveying operations when the developing device is used over a long time or at a high speed.
Particularly in the nonmagnetic single-component developing method, the toner contacts friction-charged members such as the developing sleeve or the layer thickness restricting member only for a very short time. Therefore, there is a higher chance of creating low charged toner or reversely charged toner than in the two-component developing method. Furthermore, the layer thickness of toner on a toner conveying member, which conveys the toner to the image carrier, needs to be as thin as possible. Accordingly, the toner conveying member receives a force from the layer thickness restricting member, which pushes outer additives on the surface of the toner particles inside the toner particles. This significantly deteriorates the chargeability and the flowability of the toner.
To solve the above problems, technologies are disclosed in, for example, Japanese Patent Application Laid-Open No. H08-122559 and Japanese Patent Application Laid-Open No. 2005-062215.

Toner change and flow stabilizing developing device, process cartridge, and image forming apparatus


A tool head includes a first frame having a first arm and a second arm extending from a base to a distal end. The tool head may also include a first blade in the frame between the first arm and the second arm. The first blade is movable from the base toward the distal end. The tool head further includes a second frame hingedly coupled to the first arm. The second frame may include a second blade. The second frame is configured to rotate between a closed-frame position and an open-frame position. The tool head further includes a trip lever hingedly coupled to the first arm and configured to rotate between an open-lever position and a closed-lever position. The trip lever is in the open-lever position when the second frame is in the closed-frame position and the trip lever is in the closed-lever position when the second frame is in the open-frame position.

Unless otherwise indicated herein, the materials described in this section are not prior art to the claims and are not admitted to be prior art by inclusion in this section.
Hydraulic tools can be employed to provide a user with a mechanical advantage. For example, a hydraulic tool may take the form of a cutting device having blades for cutting an object into separate parts. As another example, a hydraulic tool may take the form of a crimping device for making crimping connections, thereby conjoining two separate pieces by deforming one or both pieces in a way that causes them to hold together.


A method of manufacturing an optical lens, the method comprising the steps of blocking a lens member at a first position on a blocker; determining the first position of the lens member with respect to the blocker; comparing the first position of the lens member with a predetermined position in order to determine a positioning error between the first position and the predetermined position; determining a surface position of the surface to be manufactured with respect to the blocker according to the positioning error; and configuring operational parameters of a lens manufacturing tool in order to manufacture a surface according to the determined surface position such that the desired optical properties of the optical lens are respected. The invention further relates to an apparatus for manufacturing an optical lens.

An optical lens is typically made of plastic or glass material and generally has two opposing surfaces which co-operate with one another to converge or diverge light according to a required corrective prescription. When the positioning or shape of one of these surfaces with respect to the other is inaccurate, optical errors can be created.
Manufacturing of an optical lens to the required prescription requirements typically includes machining the surface of a semi finished lens or lens blank. Typically, a semi-finished lens has a finished front surface and an unfinished back surface. By machining the back surface of the lens to remove material, the required shape and positioning of the back surface with respect to the front surface for the desired corrective prescription can be generated. Further surfacing operations of an optical lens can include chamfering, bevelling, polishing, or coating the surface of a lens member in order to modify the optical surface. Cribbing of the optical lens involves providing the peripheral edge of the optical lens with the desired contour for the finished optical or ophthalmic lens.
During manufacturing of the lens it is important that the semi finished lens is securely maintained at a correct positioning on a support block during the various manufacturing operations in order to prevent the generation of optical errors.
Current techniques for ensuring that the positioning of a lens member with respect to a blocking support is as accurate as possible during manufacturing of an optical lens includes verifying the positioning during the blocking step by methods ranging from an operator visualising the lens positioning directly or by means of a camera, and then correcting the positioning if necessary to fully automated verification and positioning correcting processes. Fully automated positioning methods are becoming progressively complex and time consuming. EP 1194267 describes a method implementing machine vision and probing equipment to generate an accurate virtual entity of a lens blank. The virtual entity is used throughout the lens generation process for calculating and selecting lens angles, tool angles and tool paths that produce the best lens quality

Method and an apparatus for manufacturing an optical lens

ESSILOR INTERNATIONAL (COMPAGNIE GENERALE D'OPTIQUE)


The present invention relates to novel glucocorticoid compounds. The invention also relates to methods of using these compounds, the synthesis of these compounds, and to compositions and formulations comprising the glucocorticoid compounds, and uses thereof.

Glucocorticoids such as prednisone, dexamethasone (DEX), and budesonide are highly effective anti-inflammatory drugs. They are widely used to treat inflammation and autoimmune diseases such as asthma, arthritis, lupus, and Crohn's disease (1, 2). These drugs exert their physiologic roles through binding to the glucocorticoid receptor (GR), a ligand-activated transcriptional factor of the nuclear receptor superfamily. In the absence of glucocorticoid, GR resides in the cytoplasm and associates with chaperone proteins such as hsp90 and hsp70. The binding of hormone causes a conformational change in GR, leading to its translocation to the nucleus, where it exerts its transcriptional control activity, either activation (transactivation) or repression (transrepression). In transactivation, GR dimerizes, binds directly to a specific glucocorticoid response element, and then recruits coactivators to activate transcription. In transrepression, the general model is that GR binds other transcription factors (e.g., NF-κB, AP-1) to become indirectly tethered to their binding sites through protein-protein interactions. Upon being tethered near a target promoter, GR represses downstream gene expression (3). It is generally believed that transrepression does not require GR dimerization (4, 5).
Transrepression is the major mechanism through which glucocorticoids act as anti-inflammatory agents (6). The tethering of GR to the NF-κB/AP-1 promoter leads to the transcriptional repression of major downstream proinflammatory factors, including proinflammatory cytokines (e.g., TNF-α, IL-1β, and IL-6), chemokines (e.g., CCL2, CCL19), and enzymes associated with the onset of inflammation (e.g., COX2, MMP13, and phospholipase A2) (2). Because of their fast action and sustainable effect, glucocorticoids remain the first choice for treating inflammatory diseases. However, the long-term use of glucocorticoids, especially at high doses, has many adverse consequences, including diabetes mellitus/glucose intolerance, hypertension, obesity, and osteoporosis (7, 8). Most of these consequences are attributed to the transactivation of GR. For instance, glucocorticoids induce the genes encoding rate-limiting enzymes of the gluconeogenesis pathway in liver, glucose-6-phosphatase and phosphoenol pyruvate carboxykinase (9, 10), thus augmenting the de novo synthesis of glucose and eventually leading to weight gain or diabetes. Glucocorticoids also induce a key regulatory gene of bone development, Dickkopf-1 (DKK1), up-regulation of which leads to osteoporosis and bone loss (11). It is generally observed that many of the side effects of glucocorticoids are associated with high dose usage of glucocorticoids (12-14). For example, a "threshold pattern" was observed for the use of prednisone: at 7.5 mg per day, it causes glaucoma, depression and high blood pressure (12). These side effects are caused by GR transactivation as well as by non-target activation of other receptors such as mineralocorticoid receptor (MR), which activation cause high blood pressure (15). Thus, it is important to develop highly potent and selective glucocorticoids to reduce the unwanted side effects.
Potency and efficacy are two key pharmacokinetic parameters of glucocorticoids. While efficacy is the maximal activity a given drug can achieve, usually at maximal concentration, potency is the concentration of a given drug required to reach half maximal activity (EC50). For two glucocorticoids that have the same efficacy, a highly potent one will require a lower dose to achieve the same treatment effect (14, 15). Importantly, a glucocorticoid may have different potencies for transactivation and transrepression; for example, gene induction by GR via DEX requires a 5- to 6-fold higher glucocorticoid concentration than gene repression (16-18). This differential response provides an opportunity to develop highly potent glucocorticoids that can be used at low doses to achieve full repression of inflammation signals while with minimal transactivation activity and side effects. Finally, the development of insensitivity and resistance to glucocorticoid therapy is a major problem in treating common inflammatory diseases such as chronic obstructive pulmonary disease, rheumatoid arthritis and inflammatory bowel disease (19). Glucocorticoid resistance is also an unsolved issue for white blood cell cancers, especially childhood acute leukemia (20). Several mechanisms of glucocorticoid resistance have been identified or proposed, including a change of kinase pathways, alteration of cofactors, and loss or mutation of receptors (19, 21). One common observation is that the affinity of ligand for receptor is decreased in glucocorticoid-resistant patients. Such patients treated with highly potent glucocorticoids have shown improvement, but the effect gradually decreased (22). Therefore, there is an urgent need to develop a new generation of more potent glucocorticoids.
Cortisol is an endogenous glucocorticoid produced by the adrenal gland. Cortisol has low potency and receptor binding ability relative to the most commonly used synthetic glucocorticoid, such as DEX (23). On the other side, Mometasone Furoate (MF) is a potent glucocorticoid used to treat inflammatory skin disorder (Elocon), asthma (Asmanex), and nasal sinus inflammation (Nasonex) (24, 25). MF has a lipophilic furoate ester at the C17α position of steroid D ring, which is believed to be the origin of its high potency (26). Here the inventors determined the crystal structures of the GR LBD bound to MF and cortisol, which reveal the underlying mechanism that discriminates the ligand potency between MF and cortisol. We then used the observed structure mechanism to design several novel glucocorticoids with much improved potency and efficacy, which could serve as the starting leads for therapeutic development for treating inflammatory diseases.

Structures and mechanism for the design of highly potent glucocorticoids


A method for the production of a soldered joint between at least two contact partners (22, 23) of a bonding arrangement (21), with a formed piece of solder material (27) being arranged at a distance to the bonding arrangement. The formed piece of solder material is at least partially melted off. The at least partially melted off formed piece of solder material being thrust against a bonding arrangement in such a way that both bonding partners are wetted in a bonding area to establish an electrically conductive bonding.

U.S. Pat. No. 5,828,031 discloses a method for the production of a soldered joint between two contact partners of a bonding arrangement, with the contact partners being designed as contact surfaces that include a 90° angle. For the production of such a soldered joint, it is described to arrange a formed piece of solder material formed as a solder ball by means of a capillary between the two contact partners in such a way that the result is a contact between the two contact surfaces as well as the capillary. For this purpose, the solder ball is pressed against the contact surfaces by means of the capillary. Such contact must be maintained long enough until a melting of the solder ball by means of laser energy has effected a wetting of the contact surfaces and the resulting adhesive forces, which secure the solder material in the bonding position.
The aforementioned type of generation of the contact pressure between the solder ball and the contact surfaces requires that the capillary for the production of the soldered joint must be positioned directly in the area of the bonding arrangement. For one, this requires an extremely precise positioning of the capillary, and on the other hand, it requires a good accessibility of the bonding arrangement.

This patent is subject to a terminal disclaimer.

Method for the production of a soldered joint


Novel synthases and the corresponding nucleic acids encoding such synthases are disclosed herein. Such synthases possess an active site pocket that includes key amino acid residues that are modified to generate desired terpenoid reaction intermediates and products. Synthase modifications are designed based on, e.g., the three-dimensional coordinates of tobacco 5-epi-aristolochene synthase with or without a substrate bound in the active site.

Isoprenoid compounds are organic molecules produced by a wide range of organisms (e.g., plants, bacteria, fungi, etc). To date, over 23,000 individual isoprenoid molecules have been characterized with tens to hundreds of new structures identified each year. These molecules can fulfill a variety of roles. For example, monoterpenes can be used as fragrances and flavors. Sesquiterpenes and diterpenes can serve as pheromones, defensive agents, visual pigments, antitumor drugs, and components of signal transduction pathways. Triterpenes can serve important functions as membrane constituents and precursors of steroid hormones and bile acids. Polyprenols function as photoreceptive agents and cofactor side chains, and can also exist as natural polymers.
The diverse molecular compounds produced by the isoprenoid pathway are created from diphosphate esters of monounsaturated isoprene units. Isoprenes are added together in multiples of 2, 3, or 4 by prenyl transferases to make C10, C15, and C20 units, respectively. The C10, C15, and C20 molecules, named geranyl diphosphate (GPP), farnesyl diphosphate (FPP), and geranylgeranyl diphosphate (GGPP), respectively, serve as substrates for terpene synthases.
Terpene synthases catalyze the production of isoprenoid compounds via one of the most complex reactions known in chemistry or biology. In general, terpene synthases are moderately sized enzymes having molecular weights of about 40 to 100 kD. As an enzyme, terpene synthases can be classified as having low to moderate turnover rates coupled with exquisite reaction specificity and preservation of chirality. Turnover comprises binding of substrate to the enzyme, establishment of substrate conformation, conversion of substrate to product and product release. Reactions can be performed in vitro in aqueous solvents, typically require magnesium ions as cofactors, and the resulting products, which are often highly hydrophobic, can be recovered by partitioning into an organic solvent.
Terpene synthase genes are found in a variety of organisms including bacteria, fungi and plants. Swapping regions approximating exons between different terpene synthases has identified functional domains responsible for terminal enzymatic steps. For example, work performed on 4-epi-aristolochene synthase (TEAS) from Nicotiana tabacum (tobacco) and Hyoscyamus muticus vetispiradiene synthase (HVS) from henbane revealed that exon 4 and exon 6, respectively, were responsible for reaction product specificity. Combining functional domains resulted in novel enzymes capable of synthesizing new reaction products (U.S. Pat. No. 5,824,774).
Studies have led to proposed reaction mechanisms for isoprenoid production; see, e.g., Cane et al., 1985, Bioorg. Chem., 13:246-265; Wheeler and Croteau, 1987, Proc. Natl. Acad. Sci. USA, 84:4856-4859; and Pyun et al., 1994, Arch. Biochem. Biophys., 308:488-496. The studies used substrate analogs and suicide inhibitors (Croteau, 1994, Arch. Biochem. Biophys., 251:777-782; Cane et al., 1995, Biochemistry, 34:2471-2479; and Croteau et al., 1993, Arch. Biochem. Biophys., 307:397-404), as well as chemical-modifying reagents and site-directed mutagenesis in efforts to identify amino acids essential for catalysis (Cane et al., 1995, Biochemistry, 34:2480-2488; Rajaonarivony et al., 1992, Arch. Biochem. Biophys.+296:49-57; and Rajaonarivony et al., 1992, Arch. Biochem. Biophys., 299:77-82). However, these studies have resulted in limited success in defining the active site due to inherent limitations with these techniques.
The invention describes a method of identifying alpha-carbon atoms found in the active site of a terpene synthase and describes these atoms in three-dimensional space as well as the spatial relationships among them. The present invention also describes R-groups associated with such alpha-carbons and methods of altering these R-groups in order to create novel terpene synthases capable of generating novel reaction products.
Until the invention taught in this present application, the active site of synthase proteins, the amino acid residues located therein, the amino acid residues involved in catalysis, and the configuration of xcex1-carbons and R-groups within the active site have not been known. The current invention now teaches the structure of synthases, as well as provides the means of making and using the information obtained therefrom to develop and produce new and novel synthases having new and novel synthetic capabilities. The data generated using the methods described herein are useful for creation and production of synthase mutants that can use a variety of isoprenoid substrates and produce a variety of isoprenoid products.
In one embodiment, the invention features an isolated terpene synthase having about 20% or greater sequence identity to residues 265 to 535 of SEQ ID NO: 2. Such a synthase comprises nine xcex1-carbons having interatomic distances in Angstroms between the xcex1-carbons that are xc2x12.3 Angstroms of the interatomic distances shown in Table 6. The center point of each xcex1-carbon is positioned within a sphere having a radius of 2.3 Angstroms. The center point of each such sphere has the structural coordinates given in Table 5. Each xcex1-carbon has an associated R-group, and the synthase has an ordered arrangement of R-groups associated with each alpha-carbon other than the ordered arrangements of R-groups shown in Table 9. The synthase can have about 25% or greater sequence identity to residues 265 to 535 of SEQ ID 2, or about 35% or greater sequence identity to residues 265 to 535 of SEQ ID 2. Such a synthase can catalyse the formation of a terpenoid product from a monoterpene substrate, a sesquiterpene substrate, or a diterpene substrate. The product can be a cyclic terpenoid hydrocarbon or an acyclic terpenoid hydrocarbon. Either type of product can be hydroxylated or non-hydroxylated. The R-group associated with xcex1-carbon 1 can be selected from one of the following groups: the group consisting of Cys, Ser, and Thr, the group consisting of Phe, Tyr and Trp, the group consisting of Pro, Gly, and Ala, the group consisting of Glu and Asp, the group consisting of Met, Ile, Val and Leu, the group consisting of Arg and Lys, and the group consisting of Gln, Asn and His. R-groups associated with xcex1-carbons 2 to 9 can be any amino acid except those having the ordered arrangements of Table 9. Similarly, the R-group associated with each of xcex1-carbons 2-9 can be selected independently from the group consisting of Cys, Ser and Thr, the group consisting of Phe, Tyr and Trp, the group consisting of Pro, Gly, and Ala, the group consisting of Glu and Asp, the group consisting of Met, Ile, Val and Leu, the group consisting of Arg and Lys, and the group consisting of Gln, Asn and His. In these embodiments, R-groups associated with the remaining eight xcex1-carbons except those having the ordered arrangements of Table 9.
In some embodiments, the ordered arrangement of R-groups associated with xcex1-carbons 1 to 9 is Trp, Ile, Thr, Thr, Tyr, Leu, Cys, Thr and Phe, respectively, Ser, Ile, Thr, Thr, Tyr, Leu, Cys, Thr and Tyr, respectively, Trp, Ile, Thr, Thr, Tyr, Leu, Trp, Thr and Tyr, respectively, Ser, Ile, Thr, Thr, Tyr, Leu, Trp, Thr and Tyr, respectively, or Glu, Ile, Thr, Thr, Tyr, Leu, Cys, Thr and Tyr, respectively.
The invention also features a terpene synthase made by aligning the primary amino acid sequence of a preselected terpene synthase polypeptide to the amino acid sequence of residues 265 to 535 of SEQ ID NO: 2, mutating a nucleic acid encoding the preselected polypeptide at one or more codons for nine amino acid residues in a region of the polypeptide primary amino acid sequence having about 20% or greater sequence identity to residues 265 to 535 of SEQ ID NO: 2, the nine residues in the polypeptide aligning with residues 273, 294, 402, 403, 404, 407, 440, 519 and 520 of SEQ ID NO: 2; and expressing the mutated nucleic acid so that a mutated terpene synthase is made.
The invention also features an isolated terpene synthase having about 20% or greater sequence identity to residues 265 to 535 of SEQ ID NO: 2, the synthase comprising sixteen xcex1-carbons having interatomic distances in Angstroms between the xcex1-carbons that are xc2x12.3 Angstroms of the interatomic distances given in Table 4. The center point of each xcex1-carbon is positioned within a sphere having a radius of 2.3 Angstroms. The center point of each of the spheres has the structural coordinates given in Table 3. Each xcex1-carbon has an associated R-group, and the synthase has an ordered arrangement of R-groups other than the ordered arrangements of R-groups given in Table 8. The synthase can have about 25% or greater sequence identity to residues 265 to 535 of SEQ ID NO: 2, or about 35% or greater sequence identity to residues 265 to 535 of SEQ ID NO: 2. The synthase can catalyse the formation of a terpenoid product from a monoterpene substrate, a sesquiterpene substrate, or a diterpene substrate. The product can be, for example, a cyclic terpenoid hydrocarbon. The ordered arrangement of R-groups in the synthase associated with xcex1-carbons 1 to 16 can be Cys, Trp, Ile, Ile, Ser, Thr, Thr, Tyr, Leu, Cys, Val, Thr, Tyr, Asp, Phe and Thr, respectively.
The invention also features an isolated terpene synthase having about 20% or greater sequence identity to residues 265 to 535 of SEQ ID NO: 2, the synthase comprising nineteen xcex1-carbons having interatomic distances in Angstroms between the xcex1-carbons that are xc2x12.3 Angstroms of the interatomic distances given in Table 2. The center point of each xcex1-carbon is positioned within a sphere having a radius of 2.3 Angstroms. The center points of each sphere have the structural coordinates given in Table 1. Each xcex1-carbon has an associated R-group, and the synthase has an ordered arrangement of the R-groups other than the ordered arrangements of R-groups given in Table 7. The synthase can have about 25% or greater sequence identity to residues 265 to 535 of SEQ ID NO: 2, or about 35% or greater sequence identity to residues 265 to 535 of SEQ ID NO: 2. The synthase can catalyse the formation of a terpenoid product from a monoterpene substrate, a sesquiterpene substrate, or a diterpene substrate. The product can be, for example, a cyclic terpenoid hydrocarbon.
The invention also features an isolated protein comprising a first domain having an amino terminal end and a carboxyl terminal end. The first domain comprises amino acids that align structurally in three-dimensional space with a glycosyl hydrolase catalytic core, the glycosyl hydrolase catalytic core selected from the group consisting of amino acids 36 to 230 of glucoamylase protein databank (PDB) code 3GLY of Aspergillus awamori and amino acids 36 to 230 of endoglucanase CelD PDB code 1CLC. The isolated protein also comprises a second domain having an amino terminal end and carboxyl terminal end. The second domain comprises amino acids that align structurally in three-dimensional space with avian FPP synthase. The carboxyl terminal end of the first domain is linked to the amino terminal end of the second domain. The second domain has about 20% or greater sequence identity to residues 265 to 535 of SEQ ID NO: 2, and comprises nine xcex1-carbons having interatomic distances in Angstroms between the xcex1-carbons that are xc2x12.3 Angstroms of the interatomic distances given in Table 6. The center point of each xcex1-carbon is positioned within a sphere having a radius of 2.3 Angstroms, the center point of each sphere having the structural coordinates given in Table 5. Each xcex1-carbon has an associated R-group, and the synthase has an ordered arrangement of R-groups other than the ordered arrangements of R-groups given in Table 9. The protein can have about 25% or greater sequence identity to SEQ ID NO: 2, or about 35% or greater sequence identity to SEQ ID NO: 2. The synthase can catalyse the formation of a terpenoid product from a monoterpene substrate, a sesquiterpene substrate, or a diterpene substrate. The product can be, for example, a cyclic terpenoid hydrocarbon.
The invention also features an isolated synthase having a region with about 40% or greater sequence identity to residues 343 to 606 of SEQ ID NO: 20, wherein one or more amino acid residues of the synthase that align with amino acid residues at positions 348, 351, 372, 375, 376, 454, 479, 480, 481, 482, 485, 519, 523, 597, 600, 601, 605, 607 and 608 of SEQ ID NO: 20 are residues other than amino acids Y, L, C, I, T, Y, S, C, G, H, S, L, G, F, G, Y, D, Y and S, respectively. In some embodiments, the sequence identity can be about 20% or greater, 25% or greater, or 35% or greater. In some embodiments, one or more of the ordered arrangements of residues as given in Table 7 are not found in such a synthase.
The invention also features an isolated synthase having a region with about 40% or greater sequence identity to residues 316 to 586 of SEQ ID NO: 22, wherein one or more amino acid residues of the synthase that align with amino acid residues at positions 321, 324, 345, 348, 349, 427, 452, 453, 454, 455, 458, 492, 496, 569, 572, 573, 577, 579 and 580 of SEQ ID NO: 22 are residues other than amino acids C, W, N, I, T, Y, S, I, S, G, M, L, D, A, M, L, D, H and G, respectively. In some embodiments, the sequence identity can be about 20% or greater, 25% or greater, or 35% or greater. In some embodiments, one or more ordered arrangements of residues as given in Table 7 are not found in such a synthase.
The invention also features an isolated synthase having a region with about 40% or greater sequence identity to residues 352 to 622 of SEQ ID NO: 58, wherein one or more amino acid residues of the synthase that align with amino acid residues at positions 357, 360, 381, 384, 385, 463, 487, 488, 489, 490, 493, 528, 532, 606, 609, 610, 614, 616 and 617 of SEQ ID NO: 58 are residues other than amino adds Y, M, C, V, T, F, V, S, S, G, I, L, G, F, V, Y, D, Y and T, respectively. In some embodiments, the sequence identity can be about 20% or greater, 25% or greater, or 35% or greater. In some embodiments, one or more of the ordered arrangements of residues as given in Table 7 are not found in such a synthase.
The invention also features an isolated synthase having a region with about 40% or greater sequence identity to amino acid residues 272 to 540 encoded by SEQ ID NO: 33, wherein one or more amino acid residues of the synthase that align with amino acid residues at positions 277, 280, 301, 304, 305, 383, 408, 409, 410, 411, 414, 448, 452, 524, 527, 528, 532, 534 and 535 encoded by SEQ ID NOS: 33 are residues other than amino adds G, W, I, A, S, Y, T, S, G, Y, L, C, D, M, L, Y. D, Y and T, respectively. In some embodiments, the sequence identity can be about 20% or greater, 25% or greater, or 35% or greater. In some embodiments, one or more of the ordered arrangements of residues as given in Table 7 are not found in such a synthase.
The invention also features an isolated synthase having a region with about 40% or greater sequence identity to residues 319 to 571 of SEQ ID NO: 42, wherein one or more amino acid residues of the synthase that align with amino acid residues at positions 324, 327, 348, 351, 352, 430, 455, 456, 457, 458, 461, 495, 499, 571, 574, 575, 579, 581 and 582 of SEQ ID NO: 42 are residues other than amino acids I, W, V, I, S, Y, T, T, G, L, V, I, N, T, S, Y, D, Y, and T, respectively. In some embodiments, the sequence identity can be about 20% or greater, 25% or greater, or 35% or greater. In some embodiments, one or more of the ordered arrangements of residues as given in Table 7 are not found in such a synthase.
The invention also features an isolated synthase having a region with about 40% or greater sequence identity to residues 579 to 847 of SEQ ID NO: 44, wherein one or more amino acid residues of the synthase that align with amino acid residues at positions 584, 587, 606, 609, 610, 688, 713, 714, 715, 716, 719, 753, 757, 831, 834, 835, 839, 841 and 842 of SEQ ID NO: 44 are residues other than amino acids V, S, G, Q, V, Y, S, V, G, L, C, W, N, V, F, Y, D, Y and G, respectively. In some embodiments, the sequence identity can be about 20% or greater, 25% or greater, or 35% or greater. In some embodiments, one or more of the ordered arrangements of residues as given in Table 7 are not found in such a synthase.
The invention also features an isolated synthase having a region with about 40% or greater sequence identity to residues 495 to 767 of SEQ ID NO: 46, wherein one or more amino acid residues of the synthase that align with amino acid residues at positions 500, 503, 524, 527, 528, 606, 631, 632, 633, 634, 637, 674, 678, 751, 754, 755, 759, 761 and 762 of SEQ ID NO: 46 are residues other than amino acids F, L, A, Q, T, Y, S, I, G, Q, L, S, D, T, I, F, D, F and G, respectively. In some embodiments, the sequence identity can be about 20% or greater, 25% or greater, or 35% or greater. In some embodiments, one or more of the ordered arrangements of residues as given in Table 7 are not found in such a synthase.
The invention also features an isolated synthase having a region with about 40% or greater sequence identity to residues 295 to 564 of SEQ ID NO: 48, wherein one or more amino add residues of the synthase that align with amino acid residues at positions 300, 303, 324, 327, 328, 406, 431, 432, 433, 434, 437, 471, 475, 548, 551, 552, 556, 558 and 559 of SEQ ID NO: 48 are residues other than amino acids Y, W, A, C, T, Y, S, S, G, M, L, G, D, L, I, Y, D, L and Y, respectively. In some embodiments, the sequence identity can be about 20% or greater, 25% or greater, or 35% or greater. In some embodiments, one or more of the ordered arrangements of residues as given in Table 7 are not found in such a synthase.
The invention also features an isolated synthase having a region with about 40% or greater sequence identity to residues 307 to 578 of SEQ ID NO: 50, wherein one or more amino acid residues of the synthase that align with amino acid residues at positions 312, 315, 336, 339, 340, 419, 444, 445, 446, 447, 450, 484, 488, 562, 565, 566, 570, 572 and 573 of SEQ ID NO: 50 are residues other than amino acids F, W, A, M, T, Y, N, T, G, M, L, S, D, I, M, Y, D, F and S, respectively. In some embodiments, the sequence identity can be about 20% or greater, 25% or greater, or 35% or greater. In some embodiments, one or more of the ordered arrangements of residues as given in Table 7 are not found in such a synthase.
The invention also features an isolated synthase having a region with about 40% or greater sequence identity to residues 264 to 533 of SEQ ID NO: 52, wherein one or more amino acid residues of the synthase that align with amino acid residues at positions 269, 272, 293, 296, 297, 375,401, 402, 403, 404, 407, 441, 445, 517, 520, 521, 525, 527 and 528 of SEQ ID NO: 52 are residues other than amino acids C, W, L, T, S, Y, S, A, G, Y, I, A, N, A, L, Y, D, Y and S, respectively. In some embodiments, the sequence identity can be about 20% or greater, 25% or greater, or 35% or greater. In some embodiments, one or more of the ordered arrangements of residues as given in Table 7 are not found in such a synthase.
The invention also features an isolated synthase having a region with about 40% or greater sequence identity to residues 585 to 853 of SEQ ID NO: 56, wherein one or more amino acid residues of the synthase that align with amino acid residues at positions 590, 593, 614, 617, 618, 696, 721, 722, 723, 724, 727, 761, 765, 837, 840, 841, 845, 847 and 848 of SEQ ID NO: 56 are residues other than amino acids I, S, S, T, V, Y, S, I, A, L, V, G, N, M, F, Y, D, L and T, respectively. In some embodiments, the sequence identity can be about 20% or greater, 25% or greater, or 35% or greater. In some embodiments, one or more of the ordered arrangements of residues as given in Table 7 are not found in such a synthase.
The invention also features an isolated synthase having a region with about 40% or greater sequence identity to residues 307 to 574 of SEQ ID NO: 54, wherein one or more amino acid residues of the synthase that align with amino acid residues at positions 312, 315, 336, 339, 340, 418, 443, 444, 445, 446, 449, 483, 487, 560, 563, 564, 566, 568 and 569 of SEQ ID NO: 54 are residues other than amino adds C, W, I, I, T, Y, S, I, S, A, I, L, D, A, I, Y, D, D and G, respectively. In some embodiments, the sequence identity can be about 20% or greater, 25% or greater, or 35% or greater. In some embodiments, one or more of the ordered arrangements of residues as given in Table 7 are not found in such a synthase.
The invention also features an isolated synthase having a region with about 40% or greater sequence identity to residues 309 to 577 of SEQ ID NO: 24, wherein one or more amino add residues of the synthase that align with amino acid residues at positions 314, 317, 338, 341, 342, 420, 446, 447, 448, 449, 452, 485, 489, 560, 563, 564, 569, 571 and 572 of SEQ ID NO: 24 are residues other than amino acids C, W, N, V, T, Y, I, G, G, I, L, L, D, A, I, Y, D, F and G, respectively. In some embodiments, the sequence identity can be about 20% or greater, 25% or greater, or 35% or greater. In some embodiments, one or more of the ordered arrangements of residues as given in Table 7 are not found in such a synthase.
The invention also features an isolated synthase having a region with about 40% or greater sequence identity to residues 315 to 584 of SEQ ID NO: 26, wherein one or more amino acid residues of the synthase that align with amino acid residues at positions 320, 323, 344, 347, 348, 426, 451, 452, 453, 454, 457, 492, 496, 568, 571, 572, 576, 578 and 579 of SEQ ID NO: 26 are residues other than amino acids S, W, I, A, T, Y, S, V, A, S, I, L, D, A, I, Y, D, F, and G, respectively. In some embodiments, the sequence identity can be about 20% or greater, 25% or greater, or 35% or greater. In some embodiments, one or more of the ordered arrangements of residues as given in Table 7 are not found in such a synthase.
The invention also features an isolated synthase having a region with about 40% or greater sequence identity to residues 265 to 536 of SEQ ID NO: 28, wherein one or more amino acid residues of the synthase that align with amino acid residues at positions 270, 273, 294, 297, 298, 376, 401, 402, 403, 404, 407, 440, 444, 518, 521, 522, 528, 530 and 531 of SEQ ID NO: 28 are residues other than amino adds A, W, V, C, G, F, T, S, C, I, M, G, N, C, S, Y, D, Y and S, respectively. In some embodiments, the sequence identity can be about 20% or greater, 25% or greater, or 35% or greater. In some embodiments, one or more of the ordered arrangements of residues as given in Table 7 are not found in such a synthase.
The invention also features an isolated synthase having a region with about 40% or greater sequence identity to residues 342 to 612 of SEQ ID NO: 30, wherein one or more amino acid residues of the synthase that align with amino acid residues at positions 347, 350, 371, 374, 375, 453, 478, 479, 480, 481, 483, 518, 522, 596, 599, 600, 604, 606 and 607 of SEQ ID NO: 30 are residues other than amino acids F, L, C, V, T, Y, S, S, A, Y, V, L, G, L, L, Y, D, F and S, respectively. In some embodiments, the sequence identity can be about 20% or greater, 25% or greater, or 35% or greater. In some embodiments, one or more of the ordered arrangements of residues as given in Table 7 are not found in such a synthase.
The invention also features an isolated synthase having a region with about 40% or greater sequence identity to residues 273 to 541 of SEQ ID NO: 32, wherein one or more amino acid residues of the synthase that align with amino acid residues at positions 278, 281, 302, 305, 306, 384, 409, 410, 411, 412, 415, 448, 452, 524, 527, 528, 533, 535 and 536 of SEQ ID NO: 32 are residues other than amino acids C, W, I, I, S, Y, T, S, T, Y, L, C, D, I, T, Y, D, Y and T, respectively. In some embodiments, the sequence identity can be about 20% or greater, 25% or greater, or 35% or greater. In some embodiments, one or more ordered arrangements of residues as given in Table 7 are not found in such a synthase.
The invention also features a method for making a terpene synthase, comprising identifying, in a preselected polypeptide having a region with 20% or greater sequence identity to residues 265 to 535 of SEQ ID NO: 2, nine amino acid residues whose xcex1-carbons have interatomic distances in Angstroms between the xcex1-carbons that are xc2x12.3 Angstroms of the interatomic distances given in Table 6. The center point of each xcex1-carbon is positioned within a sphere having a radius of 2.3 Angstroms. The center point of each sphere has the structural coordinates given in Table 5. The method then comprises synthesizing a polypeptide that is modified from the preselected polypeptide. The modified polypeptide has one or more R-groups associated with the nine xcex1-carbons other than the R-groups associated with the xcex1-carbons in the preselected polypeptide. The synthesizing step can comprise the formation of a nucleic acid encoding the preselected polypeptide in which the coding sequence for one or more amino acids corresponding to the nine xcex1-carbons is replaced by a coding sequence that codes for an amino acid different from the amino acid present in the preselected polypeptide. The preselected polypeptide can be, for example, any one of the polypeptides given in SEQ ID NOS: 2, 4, 6, 8, 10, 12, 20, 22, 24, 26, 28, 30, 32, 34-40, 42, 44, 46, 48, 50, 52, 54, 56, or 58.
The invention also features a method of using a terpene synthase, comprising identifying, in a preselected polypeptide having a region with 20% or greater sequence identity to residues 265 to 535 of SEQ ID NO: 2, amino acid residues at nine positions that align with amino acid residues 273, 294, 402, 403, 404, 407, 440, 519 and 520 of SEQ ID NO: 2; and synthesizing a polypeptide that is modified from the preselected polypeptide. The novel polypeptide is modified by having amino add residues at one or more of the nine positions other than the amino acid residues present in the preselected polypeptide. In some embodiments, the identifying step can comprise identifying sixteen amino acid residues in the preselected polypeptide that align with amino acid residues 270, 273, 294, 297, 298, 402, 403, 404, 407, 440, 516, 519, 520, 525, 527 and 528 of SEQ ID NO: 2, and the synthesizing step can comprise synthesizing a polypeptide that is modified from the preselected polypeptide, the modified polypeptide having amino acid residues at one or more of the sixteen positions other than the amino acid residues present in the preselected polypeptide. In some embodiments, the identifying step can comprise identifying nineteen amino acid residues in the preselected polypeptide that align with amino acid residues 270, 273, 294, 297, 298, 376, 401, 402, 403, 404, 407, 440, 444, 516, 519, 520, 525, 527 and 528 of SEQ ID NO: 2, and the synthesizing step can comprise synthesizing a polypeptide that is modified from the preselected polypeptide, the modified polypeptide having amino acid residues at one or more of the nineteen positions other than the amino acid residues present in the preselected polypeptide. The synthesizing step can comprise the formation of a nucleic acid encoding the preselected polypeptide in which the coding sequence in the nucleic acid coding for one or more of the identified amino acid residues is replaced by a coding sequence that encodes an amino acid different from the amino acid present in the preselected polypeptide. The preselected polypeptide can be, for example, any one of the polypeptides given in SEQ ID NOS: 2, 4, 6, 8, 10, 12, 20, 22, 24, 26 28, 30, 32, 34-40, 42, 44, 46, 48, 50, 52, 54, 56, or 58. The method can further comprise: contacting the modified polypeptide with an isoprenoid substrate under conditions effective for the compound to bind the polypeptide; and measuring the ability of the modified polypeptide to catalyze the formation of a reaction product from the isoprenoid substrate. The isoprenoid substrate can be a monoterpene, a sesquiterpene, or a diterpene.
The invention also features a method of making a terpene synthase, comprising creating a population of nucleic acid molecules that encode polypeptides, the population having members that differ from one another at one or more of nine codons specifying amino acids of a preselected terpene synthase having a region with about 20% or greater sequence identity to residues 265 to 535 of SEQ ID NO: 2, xcex1-carbons of the nine amino acids having interatomic distances in Angstroms between the xcex1-carbons that are xc2x12.3 Angstroms of the interatomic distances given in Table 6. The center point of each xcex1-carbon is positioned within a sphere having a radius of 2.3 Angstroms, and the center point of each sphere has the structural coordinates given in Table 5. In some embodiments, the codons specify amino acids as described in Tables 1-2 or 3-4 of a preselected terpene synthase. A portion, or all, of the nucleic acid population is expressed so that a population of polypeptides is made. At least one member of the population of polypeptides is a mutant terpene synthase. The expressing step can comprise in vitro transcription and in vitro translation of the nucleic acid population. In some embodiments, the expressing step comprises cloning members of the nucleic acid population into an expression vector, introducing the expression vector into host cells and expressing the cloned nucleic acid population members in the host cells so that the population of polypeptides is made. The preselected terpene synthase polypeptide can be a monoterpene synthase, a sesquiterpene synthase, or a diterpene synthase. The host cells can be prokaryotic cells or eukaryotic cells, including, without limitation, bacterial cells, fungal cells, and animal cells, e.g., mammalian cells or insect cells. The host cells can also be plant cells, e.g., a cell from a Graminaceae plant, a cell from a Legumineae plant, a cell from a Solanaceae plant, a cell from a Brassicaeae plant or a cell from a Conifereae plant.
The invention also features a nucleic acid encoding a synthase as described herein, and a host cell containing such a nucleic acid. The invention also features a transgenic plant containing such a nucleic acid, or a transgenic animal cell culture containing such a nucleic acid.
In some embodiments, a synthase polypeptide of the invention comprises a domain that contains an active site comprised of nine xcex1-carbon atoms having the coordinates of Table 5, and interatomic distances between the xcex1-carbons xc2x12.3 angstroms of the distances given in Table 5. The xcex1-carbon atoms align structurally in three dimensional space in the presence or absence of bound substrate or substrate analogue, with avian FPP synthase. In another embodiment, a synthase of this invention comprises the following: (i) a first domain containing amino acid residues that align in three-dimensional space (in solution or crystal form, and either having a bound or unbound substrate) with a glycosyl hydrolase catalytic core selected from the group consisting of (a) amino acids 36-230 of glycosyl hydrolase (PDB code 3GLY) of Aspergillus awarmori, and (b) amino acids 36-230 of endogluconase CellB (PDB code 1CLC), and (ii) a second domain that aligns structurally in three dimensional space with or without substrate or substrate analogues bound in the active site with avian FPP synthase. The second domain contains an active site comprised of nine, sixteen or nineteen xcex1-carbon atoms having the structural coordinates and interatomic distances of Tables 1-2, 3-4 or 5-6. These xcex1-carbon atoms have R-groups attached thereto that can interact, either directly or indirectly, with an isoprenoid substrate.
The invention also features a method for generating mutant terpene synthases possessing catalytic activity. The method comprises the steps of (a) providing a crystallographic model of a preselected catalytically active terpene synthase having an active site, and (b) using the model to design a terpene synthase having at least one altered R-group in the active site relative to the preselected synthase. The invention also features terpene synthases having altered substrate specificity, methods of making the same, and procedures for generating three-dimensional structures thereof.
Although methods and materials similar or equivalent to those described herein can be used to practice the invention, suitable methods and materials are described below. All publications, patent applications, patents and other references mentioned herein are incorporated by reference in their entirety.
Other aspects, embodiments, advantages, and features of the present invention will become apparent from the specification.

University of Kentucky Research Foundation

The Salk Institute for Biological Studies


A reversible post hole digger apparatus powered by a power takeoff shaft includes a transmission providing a reverse gear and a forward gear in a single housing. The apparatus has a power head disposed between a shaft connected to the power takeoff and an output shaft driving an auger. A gear box within the power head contains a main shaft which carries forward and reverse pinion gears at opposite ends and has a central portion with an external spline connector. The pinion gears are activated by a central spline-containing slide. Movement of the slide, carried out by means of a shift lever engaging a fork with a rack and pinion device, provides connection to forward, reverse and neutral positions on the shaft. Upper and lower ring gears drive an output shaft in a selected direction.

Post hole diggers mounted on a three-point hitch of a tractor and connected to the tractor power takeoff are highly effective in digging post holes, but inclusion of a mechanism to reverse rotation of the auger is needed in case underground obstacles such as strong roots or rocks are encountered. Various approaches have been taken, including use of a kit or adapter including a gear transmission providing forward and reverse capability, with this mechanism being placed outside of the power head of the system. It is desired to include a reversing mechanism within the power head, with this mechanism being self-contained in a common housing or case, so that such capability is provided for in initial design and manufacturing steps.

Reversible power takeoff driven post hole digger


A screw tightening type connector having a female connector and a male connector fitted in the female connector. The female connector is provided with a female screw body, while a male screw body is provided on the male connector. The male connector is screwed into the female screw body and is tightened whereby the female connector and the male connector are fitted in each other. A rotational-force imparting section is provided for imparting a rotational force to the male screw body. The rotational-force imparting section has a rotary shaft extending in a direction intersected with a fitting direction of the male connector into the female connector. A rotational-force transmitting section is provided for converting the rotational force from the rotational-force imparting section to a rotational force in a direction intersected with the rotary shaft to transmit the rotational force to the male screw body.

The present invention relates to a screw tightening type connector in which a bolt provided on a connector housing of a male connector is screwed into a nut provided on a fitting hood section of a female connector and is tightened, whereby the male connector is fitted in and retained in the female connector.
FIG. 1 of the attached drawings shows a conventional screw tightening type connector I which has been proposed in Japanese Patent Laid-Open No. 63-13283. As shown in FIG. 1, the screw tightening type connector 1 comprises a male connector 3 and a female connector 9 having a fitting hood section 7 in which a connector housing 5 of the male connector 3 is fitted.
A plurality of terminal accommodating chambers (not shown) are formed in the connector housing 5 of the male connector 3. Female terminal elements (not shown) are accommodated respectively in the terminal accommodating chambers. Moreover, a through bore 17 is formed at a substantially central portion of the connector housing 5 of the male connector 3, along a fitting direction of the connector housing 5 into the fitting hood section 7. A bolt 11 is inserted into the through bore 17 such that a male screw portion 17a is located or positioned adjacent to the fitting hood section 7, at a location within the through bore 17. The bolt 11 is inserted also such that a bolt head 15 serving as a rotational-force imparting section is located adjacent to a location where a plurality of wires are drawn out of the connector housing 5. Further, a wire protecting cover 12 is fixedly mounted by fixing means (not shown) at a location adjacent to a side where the wires 19 of the connector housing 5 are drawn. Thus, a plurality of wires 19 drawn from a location within the terminal accommodating chambers (not shown) in the connector housing 5 are bent substantially perpendicularly.
A plurality of terminal accommodating chambers (not shown) are formed in a housing section 23 which is formed integrally with the fitting hood section 7 of the female connector 9. A plurality of male terminal elements (not shown) are accommodated respectively in the terminal accommodating chambers. The male terminal elements have respective forward end portions thereof which project into the fitting hood section 7. Under a condition that the connector housing 5 of the male connector 3 is fitted in the fitting hood section 7, the forward end portions of the male terminal elements are fitted respectively in the female terminal elements and are electrically connected thereto. Moreover, a support section 25 is provided in projection on a substantially central portion within the fitting hood section 7 of the female connector 9. A nut 13 serving as a female screw body is embedded in the support section 25. An opening 25a in communication with the female threaded portion of the nut 13 is formed in the forward end portion of the support section 25.
Fitting of the male connector 3 into the female connector 9 is executed as follows. That is, as shown in FIG. 2A, the connector housing 5 is inserted into the fitting hood section 7. The forward end portion of the bolt 11 serving as a male screw body is inserted into the opening 25a in the support section 25. The bolt head 15 of the bolt 11 and an engaging portion 29 at the forward end of, for example, an impact wrench 27 serving as a jig for imparting the rotational force are engaged with each other. Rotation of the impact wrench 27 imparts the rotational force to the bolt 11 so that the bolt 11 is screwed into the nut 13.
The bolt 11 is further rotated and tightened whereby the connector housing 5 is inserted into a deep portion within the fitting hood section 7 and is fitted therein. Under a condition that the connector housing 5 is perfectly fitted in the fitting hood section 7, the connector housing 5 is perfectly fitted into the fitting hood section 7 and is retained by a tightening or fastening condition between the bolt 11 and the nut 13 as illustrated in FIG. 2B. Thus, the female terminal element and the male terminal element are electrically connected to each other.
However, the screw tightening type connector 1 having no protecting cover has the following problem. That is, since the bolt head 15 of the bolt 11 is located or positioned along the fitting direction (a direction a indicated by the arrow) of the connector housing 5 into the fitting hood section 7, the wires 19 drawn out of the terminal accommodating chambers stand in the way. Thus, tightening operability of the bolt 11 due to the impact wrench 27 is inferior or is deteriorated.
Furthermore, there is the following problem. That is, since the bolt head 15 is positioned adjacent to the location where the wires are drawn out of the connector housing 5, a protective cover 21 for protecting the wires from the impact wrench 27 is required. Thus, a cost of the connector 1 rises.


An image bearing member of an image forming apparatus is heated both during an image forming operation and during an inoperative condition. At least two developing sleeves are opposed to the image bearing member. An angular difference between an angle by which one of the developing sleeves is rotated until any point on the image bearing member reaches a first position where a distance between the one developing sleeve and the image bearing member is minimum, and an angle by which the other developing sleeve is rotated until the point on the image bearing member reaches a second position where a distance between the other developing sleeve and the image bearing member is minimum, becomes (2.pi./S).times.k (rad.), where S is the number of the developing sleeves and k is an integral number excluding multiples of S.

1. Field of the Invention
The present invention relates to an image forming apparatus for developing an electrostatic latent image to form a visualized image.
2. Related Background Art
It is practical that an image bearing member such as an electrophotographic is heated to a predetermined temperature (for example, about 40.degree. C.) by a heater disposed within the image bearing member in order to prevent the occurrence of image flow due to the adhesion (dewing) of moisture in the air to the image bearing member bearing an electrostatic latent image, to improve the photosensitivity of the image bearing member and to stabilize the surface potential of the image bearing member.
The heater heats the image bearing member to keep the image bearing member at a predetermined temperature not only during the image forming operation, but also during an inoperative condition of the image forming apparatus so that an image forming operation can be started at any time.
A developing device for developing the electrostatic latent image has a developing sleeve arranged in a confronting relation to the image bearing member. During the image forming operation, the developing sleeve is rotated to apply developer to the image bearing member; whereas, in the inoperative condition, the developing sleeve is stopped, in a position opposite the image bearing member.
As mentioned above, since the image bearing member is being heated by the heater even in the inoperative condition, only a surface of the stopped developing sleeve which is opposed to the image bearing member is subjected to radiant heat from the image bearing member. Consequently, since a portion of the surface of the developing sleeve which is opposed to the image bearing member is thermally expanded, and the remaining surface of the developing sleeve is not thermally expanded, as shown in FIG. 1B, the developing sleeve 15 is deformed to have slight deflection. (Note, the deflection of the developing sleeve is exaggerated in FIG. 1B to facilitate understanding of this feature). After the developing sleeve is rotated, since the whole peripheral surface of the developing sleeve is uniformly subjected to the radiant heat from the heater 21 in the image bearing member 3, the developing sleeve gradually returns to its original straight condition as shown in FIG. 1A.
If the developing sleeve starts to rotate from the deflected condition as shown in FIG. 1B, then a minimum distance X between the image bearing member 3 and the developing sleeve 15 will vary periodically. One period (cycle) corresponds to one revolution of the developing sleeve 15. If the distance X is periodically varied, an amount of the developer applied from the developing sleeve 15 to the image bearing member 3 will also be periodically changed, because the intensity of an electric field generated between the image bearing member and the developing sleeve by applying the developing bias voltage to the developing sleeve will be periodically varied in response to the variation of the distance X. In any case, the shorter the distance X, the greater the developer amount applied to the image bearing member 3, and the longer the distance X, the smaller the developer amount applied to the image bearing member. Therefore, a periodic density irregularity will occur in the developed image. Such density irregularity will be noticeable particularly in a developing device wherein the developer is transferred from a developing sleeve 15 to an image bearing member 3 by scattering the developer without contacting a layer of the developer carried on the developing sleeve 15 with the image bearing member 3.

Image forming apparatus which reduces or eliminates density irregularity due to thermal deformation of a developing sleeve


An arrangement for measuring a thickness of a sheet article during a sheet article transportation, especially for measuring the thickness of an X-ray sheet film in an X-ray cassette loading and unloading device, has a magnet carrier arranged in a spring-biased manner on a sheet article transportation path perpendicularly to one side of the transportation path, a permanent magnet arranged on the magnet carrier near the first side of the magnet transportation path, at least one roller body arranged on the magnet carrier rotatably in a transportation direction of the sheet aarticle, a probe carrier fixedly arranged parallel to a second side of the transportation path opposite to the matnet carrier, a Hall probe arranged on the probe carrier opposite to the permanent magnet, at least one roller body arranged on the probe carrier. The probe carrier has a number of the roller bodies which corresponds to a number of the roller bodies on the magnet carrier. The roller bodies of the magnet carrier and the probe carrier rolling over one another in a plane of the transportation path. A control unit evaluates an output signal of the Hall probe.

The present invention relates to a device for measuring a thickness of sheet articles.
In device for transporting sheet articles, especially X-ray sheet film loading and unloading devices, a sheet article is moved along a transportation path by a suitable transporting roller pair. In X-ray sheet film loading and unloading devices, the X-ray sheet film is removed from the magazine, transferred to a transporting roller pair, and transported from it to a further transporting roller pair and so on until theX-ray sheet film is transported to a cassette to be loaded and placed in it. The transporting rollers can be formed as complete rollers or as roller pieces mounted on a shaft. An X-ray sheet film cassette must be loaded during this process only with an X-ray sheet film. It is however necessary to detect double and multiple films so as to prevent their transportation. In order to solve this problem of the detection of the double and multiple films several devices are proposed in the prior art.
One of the possibilities is the utilization of infrared light barriers. The presumption for this method is that the light permeability reduces when two or more X-ray sheet films lie over one another. When in a constant time interval the passing light quantity is integrated, a value is produced which is dependent on the number of the X-ray sheet films located in the region of the through light barrier. This arrangement however cannot be used for infrared-sensitive X-ray sheet film or X-ray sheet film with high transparency. German document DE-OS 3,800,249 discloses an X-ray sheet film loading and unloading device, in which a transporting roller of one transporting roller pair is turnably supported on a lever arm about a lever point. The second lever arm which is located opposite the lever arm with the transporting roller is arranged under a spring force, so that the rollers of the transporting roller pair are pressed against one another. When an X-ray sheet film is drawn from this transporting roller pair, the transporting roller supported on the lever is turned depending on the number of the drawn film sheets. The second lever arm is also turned in correspondence with the lever condition and actuates a microswitch when more than one X-ray sheet film is drawn by the transporting roller pair. This means that it can be no difference whether one or no X-ray sheet film is drawn by the transporting rollers. The arrangement for measuring the X-ray sheet film thickness disclosed in this document also has a further disadvantage in that it is mechanically very expensive, since a transporting roller must be supported turnably and it is very tolerance sensitive, with respect to the roller diameter, roller elasticity, lever size, position of the opening for the lever and roller support, etc. In addition, there is a danger that the once adjusted arrangement can lose the adjustment due to the transporting movement and the vibrations during certain times. Thereby, no reliable detection of the multiple sheets or films can be guaranteed over a long time.

Device for measuring thickness of sheet article with magnet and probe carriers provided with rollers