Disclosed is an E-beam lithography system for synchronously irradiating surfaces of a plurality of substrates. The E-beam lithography system may include a loading unit loading and unloading substrates, an alignment chamber aligning the substrates, a transfer chamber transferring the substrates from the loading unit or chambers, a lithography chamber radiating one or more electron beams onto the substrates, and a vacuum chamber creating a vacuum in the chambers. A stage may be installed in the lithography chamber such that the substrates may be mounted on the stage and radiated with one or more electron beams.

1. Field of the Invention
Example embodiments relate to an E-beam lithography system and, more particularly, to an E-beam lithography system that may synchronously irradiate surfaces of a plurality of photomasks.
2. Description of the Related Art
As semiconductor technology continues to develop, advancements in semiconductor devices, especially memory devices, are improving. That is, high speed, low power consumption, high capacity, miniaturized memory devices are being developed. As semiconductor memory devices are improved, technologies for improving integration are becoming even more important.
Improving the integration of semiconductor devices is being achieved through the development of new and/or improved circuit design techniques, materials, and various process techniques. Patterning techniques are important in improving the integration of semiconductor devices. Through the patterning technique, the pattern of unit devices, such as transistors, for example, may be finely formed on a wafer.
Patterning techniques generally include a photolithography technique and an etching technique. The photolithography technique may include fabricating a photomask and transferring a pattern to a wafer using the photomask. A photomask fabricating technique refers to a technique for forming a pattern to be transferred to a wafer on a photomask. If a pattern is formed on the photomask, the pattern should be formed to have the correct shape and a uniform size. Further, the substrate and the pattern should not have defects. The substrate may be a glass substrate, for example. Another important consideration is that an ideal layer-to-layer overlay alignment tolerance of the photomasks should be zero.
If a semiconductor chip is produced on a wafer, various patterns and unit devices may be formed using several photomasks. As a result, a finished semiconductor chip may operate correctly only if the patterns formed on the wafer using the several photomasks are precisely aligned. If even one layer is placed incorrectly and/or is misaligned, a finished unit device may not function properly, which may cause the finished semiconductor including the unit device to be inoperable and/or malfunction. Therefore, it is important for photomasks used in fabricating a semiconductor chip to have precise layer-to-layer overlay alignment.
Further, in the case of a fine pattern, duplicate exposure may be performed on a wafer using a plurality of photomasks to form one layer of a pattern, thereby further increasing the importance of layer-to-layer overlay alignment of photomasks.
In order to align the patterns formed on the photomasks, factors including registration and orthogonality may be used.
Registration refers to an alignment factor indicating how precisely the pitch, size, and interval of the patterns in the X and/or Y direction match ideal and/or computer data.
Orthogonality refers to the angles of the X and/or Y directions of the patterns. Various patterns may have several shapes created by combining lines in the X-direction and lines in the Y-direction and/or patterns in the X-direction and patterns in the Y-direction. As such, orthogonality refers to a measure representing whether the lines in the X-direction are precisely perpendicular to the lines in the Y-direction and/or whether the patterns in the X-direction are precisely perpendicular to the patterns in the Y-direction.
Herein, registration and orthogonality are referred to generically as pattern alignment. If the photomasks are overlaid, the factor representing whether the pattern alignments match each other is referred to as layer-to-layer overlay alignment and is abbreviated herein as overlay alignment.
FIGS. 1A to 1D are views schematically illustrating pattern alignment and/or computer data of two photomasks, which may be fabricated using an E-beam lithography system. FIGS. 1A to 1D are used to further describe and illustrate examples of what is referred to herein as "pattern alignment" and a "difference in pattern alignment". The drawings are somewhat exaggerated for ease of explanation. A photomask (a) and a photomask (b) may be photomasks that are separately fabricated and have the same pattern. Alternatively, the photomasks may be photomasks which are fabricated to be overlaid. Each of the photomasks may be individually fabricated.
FIG. 1A is an example view showing ideal pattern alignment, which may be computer data about patterns to be formed on photomasks.
The pattern of the photomask (a) and the pattern of the photomask (b) have an ideal pattern alignment in the X and Y directions meaning there is no error. Hence, if the two patterns shown in FIG. 1A are overlaid, the patterns of the photomask (a) and the pattern of the photomask (b) correspond. However, because the photomasks shown in FIG. 1A represent ideal pattern alignment, photomasks having the pattern alignment shown in FIG. 1A are seldom realizable.
FIG. 1B is a view comparing an example photomask (a) having ideal pattern alignment with an example photomask (b) having a difference in pattern alignment.
In FIG. 1B, the photomask (a) has ideal pattern alignment corresponding to computer data, and the photomask (b) has pattern alignment in which the registration and orthogonality are slightly different from the computer data Thus, the photomasks shown in FIG. 1B may not precisely overlay each other.
If a pattern is formed using the photomasks shown in FIG. 1B, the pattern formed by the photomask (a) would not be precisely overlaid on the pattern formed by the photomask (b) and thus, a unit device would likely not be correctly produced. Thus, a finished semiconductor device including the unit device may be inoperable. Even if the finished semiconductor device including the unit device operates, the finished semiconductor device would likely have low reliability and/or durability.
FIG. 1C is a view comparing pattern alignment of example photomasks having the same degree of difference.
In FIG. 1C, both the photomask (a) and the photomask (b) have the same pattern alignment. If the photomasks are overlaid, the patterns formed from the photomasks may precisely correspond to each other. Thus, a semiconductor device fabricated using the photomasks of FIG. 1C may operate correctly. However, it is nearly impossible to fabricate the photomasks such that the photomasks have the same degree of difference using conventional techniques.
FIG. 1D is a view illustrating two example photomasks having different degrees of difference in pattern alignment. FIG. 1D illustrates a typical example of two photomasks formed using conventional techniques.
The photomask (a) and the photomask (b) illustrated in FIG. 1D have different pattern alignment. If a semiconductor device is fabricated using the photomasks, the pattern of an upper layer is not precisely overlaid on the pattern of a lower layer. As a result finished unit devices formed using the photomask (a) and the photomask (b) shown in FIG. 1D and a semiconductor device including the unit devices may malfunction and/or be inoperable.
For example, assuming that the photomask (a) is a line pattern and the photomask (b) is a via hole pattern, lines and via holes would likely not overlay each other if the example photomasks illustrated in FIGS. 1B and 1D were used and thus, an electric connection would likely not be created. Thus, the formed unit devices may be inoperable. If an electric connection is somewhat achieved using the example photomasks illustrated in FIGS. 1B and 1D, the lines and the via holes are likely only partially overlaid and thus, an electric resistance of the unit devices formed using the example photomasks illustrated in FIGS. 1B and 1D would likely be undesirably large. In this case, the unit devices may not operate smoothly. Accordingly, the reliability and the durability of a finished semiconductor device including these unit devices would decrease.
Further, if the example photomasks illustrated in FIG. 1D are overlaid on the example photomasks having ideal pattern alignment illustrated in FIG. 1A, a normal device may be formed. However, in this case, if the example photomasks have different pattern alignment, overlay alignment tolerance may increase. For example, the overlay alignment tolerance may be twice as much as that of the pattern alignment.
Thus, reducing and/or minimizing the overlay alignment tolerance of photomasks is generally more important than reducing and/or minimizing the pattern alignment tolerance photomasks.
Pattern alignment tolerance and overlay alignment tolerance may result from the motion error of a stage of conventional photomask fabricating equipment, which may move photomasks forwards, backwards, left, and right.
A conventional E-beam lithography system for fabricating photomasks may be operated such that an irradiating system radiating an electron beam irradiates a desired and/or predetermined position; and a stage on which photomasks is mounted moves forwards, backwards, left, and right, thus radiating the electron beam on the surfaces of the photomasks to form patterns. Conventionally, the precision of the mechanical movement of the stage determines the pattern alignment and the overlay alignment.
Using conventional devices and/or techniques, it is difficult to reduce and/or solve pattern misalignment issues, which refer to the overlay alignment tolerance of photomasks or overlaid photomasks.
The pattern alignment tolerance and the overlay alignment tolerance generally do not depend on the size of a pattern to be formed, but instead have a predetermined mechanical limit. Therefore, assuming that the pattern alignment tolerance for the design rule of a pattern is the tolerance rate of the photomask, the smaller the pattern to be formed, the larger the relative tolerance of the pattern alignment and/or the overlay alignment.
As described above, the relative tolerance of the pattern alignment and/or the overlay alignment affects the manufacturing process and circuit design, so that a circuit must be designed in consideration of the pattern alignment tolerance and/or the overlay alignment tolerance. When considering the pattern alignment tolerance and/or the overlay alignment tolerance, the size of each pattern is set to be larger than an ideal size, so that the margin for the process is relatively large. This is a major factor impeding the tendency toward the miniaturization of semiconductor devices.

E-beam lithography system for synchronously irradiating a plurality of photomasks and method of fabricating photomasks using the same


A 5.times. laser beam expander lens that is well-corrected for chromatic aberration can be used without refocussing over a wavelength range from 0.365 micron to 1.3 micron.

For laser beam expanders of the prior art, a different lens was generally required for each wavelength. A need has been recognized for a single beam-expander lens that can be used over a wide wavelength band from 0.365 micron to 1.3 micron, whereby the expense and inconvenience of using different lenses for different wavelengths can be avoided.


A low-cost integrated circuit is used as a secondary side constant voltage and constant current controller. The integrated circuit has four terminals and two amplifier circuits. A first amplifier circuit is used to sense a voltage on a FB terminal and in response to cause a first current to flow through an OPTO terminal. A second amplifier circuit is used to sense a voltage between a SENSE terminal and a SOURCE terminal and in response to cause a second current to flow through the same OPTO terminal. The FB terminal is used for output voltage feedback and is also used to supply power onto the integrated circuit. The SOURCE terminal is used for output current feedback and is also used as power supply return for the integrated circuit. The cost of the integrated circuit is reduced by having only four terminals.

A circuit known as a flyback converter is a switch mode power supply circuit commonly used in applications such as AC-to-DC wall adapter power supplies and battery chargers. FIG. 1 (Prior Art) is a block diagram of a simple flyback converter 1. Flyback converter 1 operates by repeatedly closing and opening a switch 2. Closing switch 2 causes a current 3 to flow from a first input node 4, through a primary 5 of a transformer 6, through the switch 2, and to a second input node 7. In one example, a rough DC voltage is present between the first and second input nodes 4 and 7. An alternating current (AC) line voltage may, for example, be rectified by a full wave bridge rectifier (not shown) and an associated smoothing capacitor (not shown) so that the rectified and smoothed rough DC voltage is present between the first and second input nodes 4 and 7.
When switch 2 is closed, the current 3 that flows through primary 5 causes energy to be stored in transformer 6. Switch 2 is then opened. When switch 2 is opened, energy stored in transformer 6 is transferred to the output of converter 1 in the form of a pulse of current 8 that flows through a secondary 9 of transformer 6 and through a diode 10. In FIG. 1, an output capacitor 11 is connected across output terminals 12 and 13 of the converter. The pulse of current 8 charges capacitor 11. In steady state operation in a constant voltage mode, switch 2 is switched to open and close rapidly and in such a manner that the output voltage VOUT on output capacitor 11 remains substantially constant.
Flyback converter 1 of FIG. 1 is considered in further detail. Flyback converter 1 includes a primary side 14 and a secondary side 15. Primary side 14 includes a primary side controller integrated circuit 16, the switch 2, and the primary 5 of transformer 6. Secondary side 15 includes the secondary 9 of transformer 6, an optocoupler 17, a secondary side constant voltage (CV) and constant current (CC) controller integrated circuit 18, the rectifying diode 10, the output capacitor 11, and a few other discrete components. Secondary side controller 18 is an integrated circuit packaged in an IC package with eight terminals.
In the constant-voltage (CV) operational mode, the output voltage VOUT across output terminals 12 and 13 is sensed by a resistor divider. The resistor divider includes resistor 19 and 20. The center tap 21 of the resistor divider is coupled to terminal CV− of integrated circuit 18 and within integrated circuit 18 to a non-inverting input lead of a voltage control amplifier 22. The voltage control amplifier 22 compares the voltage on the center tap of the divider input to a reference voltage VREF and outputs the result of the comparison onto terminal OUT1 of integrated circuit 18. If the result of the comparison causes the voltage on terminal OUT1 to be low, then a current 23 is pulled through the optocoupler 17. The current 23 flows through current limiting resistor 24, through optocoupler 17, through a blocking diode 25, and into terminal OUT1. When current 23 flows through optocoupler 17, the optocoupler 17 causes a corresponding current 26 to flow to the primary side controller 16. This current 26 is an error current that is indicative of the voltage level on output terminals 12 and 13. Primary side controller 16 receives the error current 26 and, based on the error current, controls the on/off duty cycle of switch 2 to regulate output voltage VOUT.
In the constant-current (CC) operational mode, the current being supplied by the power supply is sensed when it returns to secondary 9. The current, referred to as IOUT, is made to flow through a sense resistor 27. The voltage drop across sense resistor 27 is therefore indicative of the magnitude of the current IOUT. The voltage drop across sense resistor 27 is sensed by a constant current amplifier 28 within integrated circuit 18. If the voltage drop is greater than a predetermined value, then constant current amplifier 28 causes the voltage on terminal OUT2 to be low. If the voltage on terminal OUT2 is low, then a current 29 is pulled through current limiting resistor 24, optocoupler 17, and blocking diode 30. The current flow 29 through optocoupler 17 causes error current 26 to flow into primary side controller 16. Error current 26 is therefore indicative of the magnitude of the current IOUT. Based on error current 26, primary side controller 16 controls the on/off duty cycle of switch 2 to regulate output current IOUT. Flyback converter 1 either operates in the constant voltage mode or in the constant current mode, depending on the loading condition. In one example, if the IOUT output current through output terminals 12 and 13 would exceed a specified current, then converter 1 operates in the constant current mode, otherwise converter 1 operates in the constant voltage mode.
Secondary side controller integrated circuit 18 has eight terminals. There are two terminals CV− and CV+ for inputs to the constant voltage amplifier 22, and one terminal OUT1 for the output of the constant voltage amplifier 22. There are two terminals CC− and CC+ for inputs to the constant current amplifier 28, and one terminal OUT2 for the output of the constant current amplifier 28. The integrated circuit is powered via a power terminal VCC and is grounded via a ground terminal GND. Integrated circuit 18 has eight terminals.
There are numerous secondary side CV-CC controller integrated circuits on the market. FIG. 2 (Prior Art) is a block diagram of a flyback converter 51 that employs one such conventional secondary side CV-CC controller integrated circuit 52, the TSM1011 manufactured by STMicroelectronics. The illustration of the circuitry within integrated circuit 52 is based on assumptions, and is a simplification. For accurate detailed information, contact STMicroelectronics.
The circuit of FIG. 2 has a similar topology to the circuit of FIG. 1, except that the current sinking outputs of the two amplifiers 53 and 54 are both coupled to the same output terminal OPTO 55. This makes an ORing function which ensures that whenever the current or the voltage exceeds their respective CC and CV regulation values, IREG and VREG, the optocoupler 56 will be activated. Accordingly, if amplifier 53 senses an overvoltage condition, i.e., VOUT>VREG, then amplifier 53 sinks current into terminal 55, thereby pulling an error current through optocoupler 56 and generating an associated error current 57 back to the primary side controller 58. If amplifier 54 senses an overcurrent condition, i.e., IOUT>IREG, then amplifier 54 sinks an error current into terminal 55, thereby pulling an error current through optocoupler 56 and generating an associated error current 57 back to the primary side controller 58. Integrated circuit 52 is powered via VCC terminal 59 and has six terminals: VCC, GND, VCTL, ICTL, and OPTO. Although the circuit of FIG. 2 works well, further improvements and cost reductions are desired.

Secondary side constant voltage and constant current controller


A liquid applicator with reservoir within a housing with a slot through which the material, or in this embodiment, the envelope flap, is drawn to activate the previously applied adhesive thereon.

1. Field of Invention
The present Invention relates to moistening and sealing envelopes. More specifically, the present invention relates to a liquid applicator for activating the adhesive on envelope flaps.
2. Prior Art
Millions of envelopes in a variety of sizes and shapes are moistened and sealed on a weekly basis in the payment of and mailing of bills, sending of notices and greetings, and the mailing of letters by homes, offices and institutions. Such moistening ranges from the use of the tongue to highly sophisticated computer controlled spray methods used for the high speed machines. The very uncertain taste of the envelope flap adhesive and the very real possibility of getting a painful cut on the tongue lead to considering a simple and convenient alternate.
U.S. Design Pat. #247,231 is an approach that provides a moistening surface but one that is subject to rapid evaporation.
U.S. Design Pat. #4,428,794 provides for a moistening method as an integral part of a sealing machine with a multiplicity of parts including moving parts.
U.S. Pat. No. #5,007,371 provides for electronic controls of a spray moistening system within a highly automated piece of machinery.
No device is known that combines the features of a manually fed moistening surface with an attractive enclosure which minimizes evaporation from the moistening surface, provides positive contact between the adhesive and moistening surfaces and minimizes any spillage from the liquid reservoir.


A first target value is set as an initial value of split point pressure, a master cylinder pressure is set as a second target value of split point pressure in a memory when ABS valves (17, 20, and 23) are operated, thereafter when a sign of locking of the rear wheels is detected, the target value is reduced even further and set in the memory, the target value is maintained for a predetermined time by timer control at every setting of a new target value, and when a braking deceleration generated while the target value is maintained in the memory, a controller (37) controls so that the target value is increased after the completion of braking. When the master cylinder pressure is higher than the target value stored in the memory, proportioning valves (26 and 27) are closed to decrease a ratio of the rear wheel braking force to the front wheel braking force, thereby always achieving appropriate control over the rear wheel braking force allocation.

This invention relates to an apparatus for controlling rear wheel braking force of a vehicle to control allocation of front wheel braking force and rear wheel braking force.
When a brake pedal is pressed down, a braking hydraulic pressure (hereinafter called a "master cylinder pressure") generated in a master cylinder is transmitted to wheel cylinders of four wheel to generate braking forces on the individual wheels.
Since, when the amount of pressing down the brake pedal is increased, the braking forces generated on the individual wheels are increased, deceleration of the vehicle increases. When the deceleration of the vehicle increases, a rear wheel load decreased, resulting in a decrease in surface gripping of rear wheels. In such a braking condition that braking (high-G braking) is generated to increase the deceleration of the vehicle, there is a problem in that, when the master cylinder pressure is distributed and transmitted almost equally to the front and wheel cylinders, the rear wheels tend to lock earlier resulting in deteriorated braking stability of the vehicle.
Therefore, a proportioning valve (PCV) has been incorporated in a brake system, which functions to transmit the master cylinder pressure, as is, to the wheel cylinder of the rear wheels when the braking force is small, and reduce increasing rate of hydraulic pressure transmitted to the wheel cylinder of the rear wheels when the master cylinder pressure exceeds a preset value, thereby preventing early locking of the rear wheels.
Furthermore, there is proposed a rear wheel braking force control apparatus in which a bypass valve for bypassing the proportioning valve, the bypass valve is opened until the above preset pressure is reached, when the preset pressure is exceeded, the bypass valve is closed to function the proportioning valve, and a split point pressure is variably set to adequately control braking force allocation to the rear wheels (Japanese Patent Application 3-315660/1991).
As a prior art example which discloses a concept similar to the above point of view, in an apparatus which is disclosed in Japanese Patent Laid-open Publication 60-47750 (DE 3329706, FR 3329706), the action of the proportioning valve is normally made effective but, when an antiskid brake system (ABS) operates, the action of the proportioning valve is invalidated by an electromagnetic valve to use the rear wheel braking force up to a locking limit.
Furthermore, Japanese Patent Laid-open Publication 1-257652 (DE 3742173, FR 2624462, GB 2213543), Japanese Patent Laid-open Publication 3-208760 (DE 4029332, GB 2238092, FR 2654401) describe an apparatus in which the action of the proportioning valve is normally invalidated by an electromagnetic valve to increase braking force allocation to the rear wheels for reducing burden to a front wheel braking apparatus, but only when the ABS system malfunctions, the electromagnetic valve is operated to effect the action of the proportioning valve, thereby ensuring safety.
However, in the former prior art example, since the braking force allocation to the rear wheels is controlled by the proportioning valve before the ABS system operates, the braking force allocation tends to be excessively lowered on a road surface with a high rear wheel locking limit, resulting in an increase in burden to the front wheel brakes. When the ABS system operates, since braking force allocation to the rear wheels is increased, a rapid locking behavior of the rear wheels occurs, and hydraulic pressure control of the ABS system tends to become unstable, leading to a deterioration of control accuracy.
In the latter prior art example, despite the braking force allocation to the rear wheels is enhanced to reduce burden to the front wheel brakes, the braking force allocation to the rear wheels is maintained at a high level also when the ABS system operates, and the control accuracy of the ABS system tends to be deteriorated as in the former prior art example. Moreover, the proportioning valve can function merely when the ABS system malfunctions, and the action of the proportioning valve cannot be effectively utilized.
Therefore, it is a primary object of the present invention to appropriately control the braking force allocation to the rear wheels in cooperation with the ABS system.

Rear wheel braking force control apparatus and control method therefor

Mitsubishi Jidosha Kogyo Kabushiki Kaisha


A lock-up clutch slip control system for controlling a lock-up clutch, which is arranged in parallel with a hydraulic power transmission for connecting a prime mover and a speed change unit, selectively into a slip state. It is decided whether or not a slip control of changing the lock-up clutch from a complete apply state to a slip state is to be executed according to the operation of lowering the output of the prime mover. The output of said prime mover is changed to suppress the output fluctuation of the prime mover when it is decided that the slip control of the lock-up clutch is to be executed.

1. Field of the Invention
The present invention relates to a system for controlling a lock-up clutch, which is arranged in parallel with a hydraulic power transmission such as a torque converter, and, more particularly, to a control system for executing a slip control to keep the lock-up clutch in a slip state.
2. Related Art
As well known in the art, the hydraulic power transmission such as the torque converter is inevitably influenced by a relative rotation between its input element and output element so that it causes deterioration in the fuel economy of the vehicle. In recent years, therefore, a lock-up clutch is arranged in parallel with the hydraulic power transmission to connect the input element and the output element directly so that the fuel economy may be improved by applying the lock-up clutch selectively to transmit the torque through the lock-up clutch in place of the hydraulic power transmission.
In short, the lock-up clutch effects a mechanically direct connection between a prime mover such as an engine and a speed change unit. Thus, the lock-up clutch transmits the fluctuation in the output torque of the prime mover as it is to the speed change unit, and may deteriorate the shocks and the booming noises. Considering the driving comfort of the vehicle, therefore, the region where the lock-up clutch can be applied is restricted. If the control is made to apply or release the lock-up clutch completely, on the other hand, the so-called "slip" in the hydraulic power transmission disappears or appears to change the output shaft torque of the vehicle. This torque change is physically felt, if extreme, as the apply shocks to degrade the driving comfort of the vehicle.
In the prior art, therefore, there has been developed a technique, in which the lock-up clutch is not only controlled to apply and release states but also set to have a slightly smaller transmission torque capacity than the input torque so that it may be brought into a slip state (i.e., a partially applied state), as disclosed in Japanese Patent Laid-Open No. 142970/1990 (i.e., JPA2-142970). The invention, as disclosed in this publication, is constructed, as will be specifically described in the following. When the lock-up clutch is to be changed from the release state to the apply state, it is controlled at first into the slip state to reduce the difference between the RPM at the input side and the RPM at the output side gradually, and the lock-up clutch is then controlled into the complete apply state.
In the system of the prior art, as described above, the running state of the vehicle comes into the lock-up region as the vehicle speed rises thereby to control the application of the lock-up clutch. This control is intended to prevent an abrupt change in the rotation, which might otherwise be caused by applying the lock-up clutch, and the shocks which might accompany the abrupt rotational change. When the lock-up clutch is set in the slip state, however, the abrupt torque fluctuation and the vibrations can be cut while the torque being transmitted at a level. Therefore, the slip control can be effectively executed not only as a transient control for applying the lock-up clutch but also in other situations. In these situations, the slip control may desirably be made together with the control of the state such as the input torque of the prime mover. In the prior art, the slip control is made exclusively on the basis of the difference between the input/output RPMs, i.e., the slip percentage so that it is not always proper. This may deteriorate the shocks or the vibrations.


Chemokine receptor antagonists, in particular, 3,7-diazabicyclo[3.3.0]octane compounds according to formula (I) are antagonists of chemokine CCR5 receptors which are useful for treating or preventing an human immunodeficiency virus (HIV) infection, or treating AIDS or ARC. The invention further provides methods for treating diseases that are alleviated with CCR5 antagonists. The invention includes pharmaceutical compositions and methods of using the compounds for the treatment of these diseases. The invention further includes processes for the preparation of compounds according to formula I.

A-M. Vandamme et al. (Antiviral Chemistry & Chemotherapy, 1998 9:187-203) disclose current HAART clinical treatments of HIV-1 infections in man including at least triple drug combinations. Highly active anti-retroviral therapy (HAART) has traditionally consisted of combination therapy with nucleoside reverse transcriptase inhibitors (NRTI), non-nucleoside reverse transcriptase inhibitors (NNRTI) and protease inhibitors (PI). These compounds inhibit biochemical processes required for viral replication. In compliant drug-naive patients, HAART is effective in reducing mortality and progression of HIV-1 to AIDS. While HAART has dramatically altered the prognosis for HIV infected persons, there remain many drawbacks to the current therapy including highly complex dosing regimes and side effects which can be very severe (A. Carr and D. A. Cooper, Lancet 2000 356(9239):1423-1430). Moreover, these multidrug therapies do not eliminate HIV-1 and long-term treatment usually results in multidrug resistance, thus limiting their utility in long term therapy. Development of new drug therapies to provide better HIV-1 treatment remains a priority.
Compounds of the present invention modulate the activity of the chemokine CCR5 receptors. The chemokines are a large family of pro-inflammatory peptides that exert their pharmacological effect through G-protein-coupled receptors. The name "chemokine", is a contraction of "chemotactic cytokines". The chemokines are a family of leukocyte chemotactic proteins capable of attracting leukocytes to various tissues, which is an essential response to inflammation and infection. Human chemokines include approximately 50 small proteins of 50-120 amino acids that are structurally homologous. (M. Baggiolini et al., Annu. Rev. Immunol. 1997 15:675-705)
Modulators of the CCR5 receptor may be useful in the treatment of various inflammatory diseases and conditions, and in the treatment of infection by HIV-1 and genetically related retroviruses. As leukocyte chemotactic factors, chemokines play an indispensable role in the attraction of leukocytes to various tissues of the body, a process which is essential for both inflammation and the body's response to infection. Because chemokines and their receptors are central to the pathophysiology of inflammatory and infectious diseases, agents which are active in modulating, preferably antagonizing, the activity of chemokines and their receptors, are useful in the therapeutic treatment of such inflammatory and infectious diseases. The chemokine receptor CCR5 is of particular importance in the context of treating inflammatory and infectious diseases. CCR5 is a receptor for chemokines, especially for the macrophage inflammatory proteins (MWP) designated MIP-1a and MIP-1b, and for a protein which is regulated upon activation and is normal T-cell expressed and secreted (RANTES).
HIV-1 infects cells of the monocyte-macrophage lineage and helper T-cell lymphocytes by exploiting a high affinity interaction of the viral enveloped glycoprotein (Env) with the CD-4 antigen. The CD-4 antigen, however appeared to be a necessary, but not sufficient requirement for cell entry and at least one other surface protein was required to infect the cells (E. A. Berger et al., Ann. Rev. Immunol. 1999 17:657-700). Two chemokine receptors, either the CCR5 or the CXCR4 receptor were subsequently found to be co-receptors along with CD4 which are required for infection of cells by the human immunodeficiency virus (HIV). The central role of CCR5 in the pathogenesis of HIV was inferred by epidemiological identification of powerful disease modifying effects of the naturally occurring null allele CCR5 Δ32. The Δ32 mutation has a 32-basepair deletion in the CCR5 gene resulting in a truncated protein designated Δ32. Relative to the general population, Δ32/Δ32 homozygotes are significantly common in exposed/uninfected individuals suggesting the role of CCR5 in HIV cell entry (R. Liu et al., Cell 1996 86(3):367-377; M. Samson et al., Nature 1996 382(6593):722-725).
The HIV-1 envelope protein is comprised of two subunits: gp120, the surface subunit and gp41, the transmembrane subunit. The two subunits are non-covalently associated and form homotrimers which compose the HIV envelope. Each gp41 subunit contains two helical heptad repeat regions, HR1 and HR2 and a hydrophobic fusion region on the C-terminus.
The CD-4 binding site on the gp120 of HIV appears to interact with the CD4 molecule on the cell surface that induces a conformation change in gp120 which creates or exposes a cryptic CCR5 (or CXCR-4) binding site, and undergoes conformational changes which permits binding of gp120 to the CCR5 and/or CXCR-4 cell-surface receptor. The bivalent interaction brings the virus membrane into close proximity with the target cell membrane and the hydrophobic fusion region can insert into the target cell membrane. A conformation change in gp41 allows the contact between the outer leaflet of the target cell membrane and the viral membrane which produces a fusion pore whereby the virus RNA is injected into the cytoplasm. Accordingly, an agent which could inhibit binding between gp120 and chemokine receptors should prevent or moderate infection in healthy individuals and slow or halt viral progression in infected patients. (B. Tomkowicz and R. G. Collman, Expert Opin. Ther. Targets 2004 8(2):65-78; J. P. Moore and R. W. Doms, Proc. Nat. Acad. Sci. USA, 2003 100(19):10598-10602)
Viral fusion and cell entry is a complex multi-step process and each step affords the potential for therapeutic intervention. These steps include (i) CD-40-gp120 interactions, (ii) CCR5 and/or CXCR-4 interactions and (iii) gp41 mediated membrane fusion. Each of these steps affords an opportunity for therapeutic intervention in preventing or slowing HIV infection
RANTES, a natural ligand for the CCR5 receptor, and an analog chemically modified on the N-terminus, aminooxypentane RANTES, were found to block HIV entry into the cells. (G. Simmons et al., Science 1997 276:276-279). Other compounds have been demonstrated to inhibit the replication of HIV, including soluble CD4 protein and synthetic derivatives (Smith, et al., Science 1987 238:1704-1707), dextran sulfate, the dyes Direct Yellow 50, Evans Blue, and certain azo dyes (U.S. Pat. No. 5,468,469). Some of these antiviral agents have been shown to act by blocking the binding of gp120, the coat protein of HIV, to its target, the CD4 glycoprotein of the cell.
T20 (Entuvirtide) is a 36 amino acid peptide corresponding to residues 643-678 in the HR2 domain of gp41. T-20 binds a transient intermediate formed interaction after interaction of gp120 and the target cell which inhibits viral fusion thereby suppressing viral replication. (J. M. Kilby et al., New Eng. J. med. 1998 4(11):1302-1307). T-20 has been approved for clinical use.
In addition to the potential for CCR5 modulators in the management of HIV infections, the CCR5 receptor is an important regulator of immune function and compounds of the present invention may prove valuable in the treatment of disorders of the immune system. Treatment of solid organ transplant rejection, graft v. host disease, arthritis, rheumatoid arthritis, inflammatory bowel disease, atopic dermatitis, psoriasis, asthma, allergies or multiple sclerosis by administering to a human in need of such treatment an effective amount of a CCR5 antagonist compound of the present invention is also possible.
The pharmacokinetic challenges associated with large molecules, proteins and peptides resulted in the establishment of programs to identify low molecular weight antagonists of CCR5. The efforts to identify chemokine modulators have been reviewed (W. Kazmierski et al. Biorg Med. Chem. 2003 11:2663-76; L. Agrawal and G. Alkhatib, Expert Opin. Ther. Targets 2001 5(3):303-326; Chemokine CCR5 antagonists incorporating 4-aminopiperidine scaffold, Expert Opin. Ther. Patents 2003 13(9):1469-1473; M. A. Cascieri and M. S. Springer, Curr. Opin. Chem. Biol. 2000 4:420-426, and references cited therein)
Takeda's program was the first to lead to fruition with the identification of TAK-779 (M. Shiraishi et al., J. Med. Chem. 2000 43(10):2049-2063). Schering has advanced Sch-351125 into Phase I/II clinical studies and reported the advance of a more potent follow-up compound, Sch-417690 into Phase I studies. (S. W. McCrombie et al., WO00066559; B. M. Baroudy et al. WO00066558; A. Palani et al., J. Med Chem. 2001 44(21):3339-3342; J. R. Tagat et al., J. Med Chem. 2001 44(21):3343-3346; J. A. Esté, Cur. Opin. Invest. Drugs 2002 3(3):379-383).

Merck has disclosed the preparation of (2S)-2-(3-chlorophenyl)-1-N-(methyl)-N-(phenylsulfonyl)amino]-4-[spiro(2,3-dihydrobenzothiophene-3,4′-piperidin-1′-yl)butane S-oxide (1) and related derivatives, trisubstituted pyrrolidines 2 and substituted piperidines 3 with good affinity for the CCR5 receptor and potent-HIV activity. (P. E. Finke et al., Bioorg. Med. Chem. Lett., 2001 11:265-270; P. E. Finke et al., Bioorg Med. Chem. Lett., 2001 11:2469-2475; P. E. Finke et al., Bioorg. Med. Chem. Lett., 2001 11:2475-2479; J. J. Hale et al., Bioorg. Med. Chem. Lett., 2001 11:2741-22745; D. Kim et al., Bioorg. Med. Chem. Lett., 2001 11:3099-3102)

WO0039125 (D. R. Armour et al.) and WO0190106 (M. Perros et al.) disclose heterocyclic compounds that are potent and selective CCR5 antagonists. UK-427857 has advanced to clinical trials and show activity against HIV-1 isolates and laboratory strains (M. J. Macartney et al., 43rd Intersci. Conf. Antimicrob. Agents Chemother. (Sep. 14-17, 2003, Abstract H-875).

Due to their rigidity and the ease of functionalization, bicyclic and tricyclic amines have proven to be useful scaffolds in drug design. Compounds based upon the 3,7-diazabicyclo[3.3.0]octane (4: R′═R″═H) are known for use in a variety of medical applications, including inter alia as migraine (as described in WO 98/06725 and WO97/11945); antibiotics (as described in WO 97/10223 and WO 96/25691, neuroleptics (as described in WO 95/15327 and WO95/13279); serotonin reuptake inhibitors (as described in WO 96/07656); thrombin inhibitors (as described in Helv. Chim. Acta 2000 83:855, Chem. & Biol. 1997 4:287 and Angew. Chem. Int. Ed. Eng 1995 34:1739); and, anxiolytic agents (J. Med. Chem. 1989 32:1024). In addition, compounds based upon 3,7-diazabicyclo[3.3.0]octane have been used in the treatment of gastrointestinal disorders (DE 39 30 266 A1) disorders of the glutaminergic system. WO 00/55143 discloses diamine compounds, including 3,7-diazabicyclo[3.3.0]octane compounds linked to an oxazolone which compounds are α-1 adrenoreceptor modulators. EP 1 122 257 (F. Ito et al.) disclose benzimidazole compounds linked to a variety bicyclic diamine compounds including diazabicyclooctanes which compounds are ORL-1 receptor agonists. The ORL-1 receptor is an opioid receptor subtype.
WO 96/07656 (J. M. Schaus and R. D. Titus) disclosed aralkyl substituted 3,7-diazabicyclo[3.3.0]octane compounds with selective reuptake inhibitory activity. WO 97/11945 (A. Madin) disclose 3-substituted 3,7-diazabicyclo[3.3.0]octane compounds, which may be further substituted at the 7-position, with selective 5-HTIDα activity. WO 01/44243 (D. Peters et al.) disclose novel heteroaryl 3-substituted-diazabicycloalkane compounds, which may be optionally substituted at the 7-position, which are muscarinic and nicotinic receptor modulators which are useful in the treating diseases associated with degeneration of the cholinergic system. The preferred embodiments include 3,7-diazabicyclo[3.3.0]octane compounds 4 wherein R′ is a heteroaryl group and R″ is hydrogen, alkyl, aryl, aralkyl or a fluorescent group.
WO 02/07523 A1 (R. Colon-Cruz et al.) discloses 3,7-diazabicyclo[3.3.0]octane compounds which are antagonists of the chemokine CCR2 and CCR3 receptors. MCP-1 is believed the natural ligand for the CCR2 receptor and interaction of the ligand with the receptor increases histamine release, calcium influx, cAMP activation, increases integrin expression and acts as a chemotactic factor for monocytes and macrophages. Compounds disclosed in the invention were claimed useful for the treatment of diseases of monocyte, lymphocyte and leukocyte accumulation and more specifically atherosclerosis, restenosis, gingivitis, psoriasis, rheumatoid arthritis, glomerulonephritis, Crohn's disease, encephalomyelitis and transplant rejection. The preferred embodiments include compounds with the generic formula 5.

WO 02/060902 A1 (M. Björsne et al.) disclose 3,7-diazabicyclo[3.3.0]octane compounds useful in the treatment of cardiac arrhythmias. The preferred embodiments include compounds with the generic formula 6.


The invention provides a highly efficient, rapid, and cost effective method of linking nucleic acid components in a predetermined order to produce a nucleic acid multicomponent construct. The invention further provides nucleic acid components, each nucleic acid component comprising a double stranded nucleic acid molecule having at least one single stranded 5xe2x80x2 or 3xe2x80x2 terminal sequence, the terminal sequence having sufficient complementarity to either a terminal sequence in a separate nucleic acid component or to a sequence in a linking nucleic acid molecule so as to allow for specific annealing of complementary sequences and linkage of the components in a predetermined order. Kits containing reagents required to practice the method of the invention are also provided.

The essence of recombinant DNA technology is the joining of two or more separate segments of DNA to generate a single DNA molecule that is capable of autonomous replication in a given host. The simplest constructions of hybrid DNA molecules involve the cloning of a DNA sequence of interest (such as DNA insert containing a natural or synthetic gene or gene fragment) into a pre-assembled cloning vector. The cloning vector includes all of the necessary components for replication of the DNA insert in a compatible host cell, e.g., promoter sequence, origin of replication sequence, termination sequence, and a selectable marker sequence. The DNA insert sequences can be derived from essentially any organism, and they may be isolated directly from the genome, from mRNA, or from previously cloned DNA sequences. Alternatively, the DNA insert sequences can be created synthetically.
Insertion of the DNA sequence of interest can be accomplished by a number of techniques. The most common technique involves restriction enzymes. A restriction enzyme recognition site that is present in both the DNA insert and the vector of interest is cleaved with a restriction enzyme to provide for appropriate termini, the termini of either the DNA insert or the vector are treated with alkaline phosphatase to remove terminal phosphates and avoid undesirable joining, and the DNA sequence of interest is inserted into the vector at the compatible sites during a ligation reaction. A restriction enzyme site present in a pre-assembled vector must be compatible with a restriction enzyme site in the DNA sequence of interest.
Alternatively, the DNA of interest can be modified to obtain compatible restriction sites by filling in of cohesive ends as appropriate, or by the ligation of an appropriate oligonucleotide linker, which can be subsequently cleaved by the restriction enzyme of interest.
Conventional cloning methods can be time consuming and often involve multiple sub cloning steps. Therefore, a need exists for developing a simple and rapid method for synthesizing and identifying an optimal construct for use in a particular application.
This invention pertains to methods for preparing multicomponent nucleic acid constructs. The method of the invention has a wide variety of applications for the expression of synthetic and naturally occurring genes or gene fragments. The invention provides integral vector elements which may be specifically selected or which may varied so as to create a collection of vectors from which optimal configurations can be selected or screened for. These integral vector elements include both vector backbone elements, which do not directly affect the expression or form of the insert gene or gene fragment, and insert modifying vector elements which alter the expression and/or form of the insert-encoded gene product. This system for the rapid and flexible assembly of specific multicomponent nucleic acid constructs is referred to as GEOS (for Genetic Engineering Operating System). GEOS methodology has numerous applications ranging from the assembly of simple circular expression vectors to the production of complex linar assemblies which function as small chromosomes. Various applications of GEOS methodology are discussed in detail below and still others will be apparent to the skilled artisan.
The invention further provides a method of linking the vector element nucleic acid components in a predetermined order so as to produce a nucleic acid multicomponent construct.
In certain preferred embodiments, the GEOS method comprises:
(a) providing the nucleic acid components to be assembled into the construct, each nucleic acid component comprising a double stranded nucleic acid molecule having at least one single stranded 5xe2x80x2 or 3xe2x80x2 terminal sequence, the terminal sequence having sufficient complementarity to a terminal sequence in a separate nucleic acid component so as to allow for specific annealing of complementary sequences and linkage of the components in a predetermined order;
(b) incubating the nucleic acid components under conditions which allow for the specific annealing and linkage of the nucleic acid components to thereby produce the nucleic acid multicomponent construct.
In another preferred embodiments, the GEOS method comprises:
(a) providing the nucleic acid components and one or more linking nucleic acid molecules to be assembled into the construct, each nucleic acid component comprising a double stranded nucleic acid molecule having at least one single stranded 5xe2x80x2 or 3xe2x80x2 terminal sequence, the terminal sequence having sufficient complementarity to a sequence in a linking nucleic acid molecule so as to allow for specific annealing of complementary sequences and linkage of the components in a predetermined order;
(b) incubating the nucleic acid components under conditions which allow for the specific annealing and linkage of the nucleic acid components to thereby produce the nucleic acid multicomponent construct.
The genetic element portion(s) of the nucleic acid components can be double- or single-stranded, though are preferably double-stranded.
In a preferred embodiment of the method, the nucleic acid components are flanked by single stranded terminal sequences and these terminal sequences are preferably non-palindromic. The nucleic acid components can be linked either directly via annealing of 5xe2x80x2 or 3xe2x80x2 complementary terminal sequences or indirectly via a linking nucleic acid molecule (e.g. an oligonucleotide or an adaptor molecule).
The nucleic acid components can be linked either simultaneously or sequentially to form the nucleic acid construct. Sequential assembly is suitable for automation. The method can be used to produce nucleic acid constructs which are functional as assembled or constructs which are used as subcomponents for the assembly of functional constructs.
The method of the invention can be used to synthesize a group of nucleic acid constructs in which one or more of the components can be substituted, in each of the constructs, with a different nucleic acid component, having the same functionality or characteristic utility. This allows for comparison of the different components and production of an optimal construct for a particular application. Toward this end, the nucleic acid components are designed and synthesized in such a way that a group of nucleic acid components belonging in the same category (i.e., having the same functionality or characteristic utility, e.g. a set of nucleic acid components encoding different promoters) possess the same terminal sequences, such that the same category nucleic acid components can be used interchangeably to assemble a nucleic acid multicomponent construct.
The nucleic acid components may also be covalently or non-covalently modified prior to or following assembly of the nucleic acid multicomponent construct. This allows for the synthesis of constructs having biological properties which cannot be obtained easily using current recombinant methods. For instance, the modification utilizes an arylboronic acid reagent, such as phenyldiboronic acid.
The method of this invention is particularly suitable for the construction of nucleic acid vectors. These include plasmid, viral, or phage vectors, or yeast artificial chromosomes. The vector can be a cloning or expression vector and can be used for the expression of cDNA or genomic libraries, genes or gene fragments, mutagenized genes, recombined fusion genes, and artificial genes. The constructs can be employed in prokaryotic, eukaryotic (mammalian or non-mammalian) expression, construction of unique cDNA libraries, protein, antibody and peptide phage display libraries. The constructs can further be employed in gene transfer, gene therapy, and the creation of transgenic organisms.
According to the method, the vector is assembled from nucleic acid components encoding a single functionality or multiple functionalities. In some applications of the invention, more than one biological function may be bundled into a single nucleic acid component. This may be desirable when, for example, one seeks to limit the overall number of components to be assembled into the GEOS construct. In one embodiment of the invention, nucleic acid components encoding an origin of replication, a selectable marker and an insert of interest are used. Depending on the type of vector desired, nucleic acid components encoding other vector functions may also be incorporated (e.g. a promoter, a transcription or translation regulatory element, etc.). An expression vector can be produced using a nucleic acid component encoding a structural gene or gene fragment of interest and additional nucleic acid components encoding regulatory elements required for expression of the gene. For example, a cDNA library expression vector is produced using nucleic acid components encoding a collection of cDNA molecules derived from poly(A)+ mRNA. Importantly, the optimization procedure of interchanging nucleic acid components described above can be used to create an optimal vector for a particular application.
The invention further provides a kit for the production of vectors. In one embodiments, the kit for the production of vectors would minimally comprise nucleic acid components encoding origins of replication and selectable markers and optionally, transcriptional regulatory sequence(s). The kit could also include nucleic acid components encoding other vector functions (e.g. a promoter, a transcription or translation regulatory element, etc.).
The invention further provides a kit for the production of vectors. The kit for the production of vectors would minimally comprise nucleic acid components encoding origins of replication, selectable markers and inserts of interest. The kit could also include nucleic acid components encoding other vector functions (e.g. a promoter, a transcription or translation regulatory element, etc.).
The method of the invention is a highly efficient, rapid, cost effective alternative to current recombinant cloning methods in that it enables users to choose from a broad array of different nucleic acid components or modified nucleic acid components when assembling any construct. The method of the invention allows the rapid construction of customized constructs without the need to use restriction enzymes.
Other features and advantages of the invention will be apparent from the following detailed description, and from the claims.

Method and kits for preparing multicomponent nucleic acid constructs


To provide an inhibitor of melanin decomposition, which inhibits decomposition of melanin in keratinocytes to accelerate accumulation of melanin in skin and hair.

It has been reported that various factors are involved in determining color of the skin or hair. Of the various factors, the amount and quality of melanin present in the epidermis are considered to greatly contribute to determining color of the skin or hair. More specifically, generation of color of the skin or hair is significantly influenced by spreading of melanin, which is produced in small organelles called melanosomes in melanin-producing cells (melanocytes), transferred to keratinocytes of the epidermis and hair follicles and distributed over the whole epidermis and hair.
Accordingly, if the amount of melanin is increased in keratinocytes by, e.g., acceleration of melanin production and inhibition of melanin decomposition, the skin turns brown and the hair turns black.
Recently, the applicant found that autophagy is involved in melanin dynamic in keratinocytes and the amount of melanin in keratinocytes is correlated with autophagy activity (Patent Literature 1). According to the finding, if the autophagy activity is inhibited, decomposition of melanin in keratinocytes is inhibited, with the result that the color of the skin or hair can be conceivably darkened.
For the skin, as one of the causes of pigment spots and freckles, acceleration of the activity of melanocytes present in the skin by, e.g., stimulation due to UV-exposure of the skin, abnormality in hormone or genetic factors, to increase melanin production is known. Because of this, whitening agents have been developed for inhibiting melanin production or degrading melanin once produced. However, the number of persons who wish to have brown skin is not small in the United States and European countries. Also, in our country, sunbathing and indoor UV irradiation have been recently in fashion mainly among the youth. In the United States and European countries, artificial tanning on a tanning bed is still popular. In contrast, harmful effects of UV have been acknowledged through enlightenment activities. Owing to this, self-tanning agents containing dihydroxyacetone as a main component are presently available on the market.
Excessive UV irradiation as mentioned above causes significant damage to the skin and may lead to the onset of skin cancer. As to a self-tanning agent, problems in effect have been pointed out. Since a self-tanning agent darkens the skin based on the Maillard reaction of the horny layer, color shade, stability of color shade and UV protection ability are not expected to be improved.
In contrast, getting gray hair is a physiological phenomenon, i.e., aging in which melanin is decreased by a change of hair-matrix melanin-producing cells; however, the mechanism of how to get gray hair has not yet been elucidated. As means for changing gray hair to black hair, a number of components preventing or improving gray hair have been reported; however, sufficient components in view of effectiveness and safety have not yet been obtained. Coloring hair with a hair dye is mainly used at present.
In the circumstances, if a component which directly acts on keratinocytes and increases the amount of melanin or accumulates melanin is found, the component can accelerate a biophylactic ability that melanin inherently has to prevent skin damage as well as darken the skin and prevent or improve gray hair.
Phenformin belongs to the biguanide drug developed as an oral antidiabetic drug. It is reported that phenformin activates autophagy through activation of AMPK (AMP-activated protein kinase) in human embryonic liver cells (HEK 293 T cells) (Non-Patent Literature 1).
Berberine is a benzylisoquinoline alkaloid contained in plants such as KIHADA and OUREN. Since berberine has, e.g., a bactericidal action against harmful enterobacteria and choleretic effect, it is used for treating, e.g., diarrhea. It was reported that berberine has an AMPK activation action (Non-Patent Literature 2); that berberine has an antioxidation and anti-inflammatory effect; and that Barberry root rich in berberine is used as a herb mixture for treating white spot (Non-Patent Literature 3).
Proguanil is an antimalarial agent for use in treating and preventing malaria and a highly safe drug used for a long time over the world.
However, it is totally unknown that phenformin, berberine and proguanil have an inhibitory action on melanin decomposition in keratinocytes.
[Patent Literature 1] International publication 2013/162012
[Non Patent Literature 1] Egan D F, et al., (2011) Science, 331: 456-461
[Non Patent Literature 2] Jeong H W, et al., (2009) Am J Physiol Endocrinol Metab, 296: E955-964
[Non Patent Literature 3] Jimi Yoon, Young-Woo Sun and Tae-Heung Kim (2011). Complementary and Alternative medicine for Vitiligo, Vitiligo-Management and Therapy, Dr. Kelly KyungHwa Park (Ed.), ISBN: 978-953-307-731-4, InTech, Available from: http://www.intechopen.com/books/vitiligo-management-and-therapy/complementary-andalternative-medicine-for-vitiligo

Abstract: An inhibitor of melanin decomposition in keratinocytes, comprising at least one selected from the group consisting of a plant extract containing berberine or a salt thereof, berberine or a salt thereof, proguanil or a salt thereof and phenformin or a salt thereof, as an active ingredient.


An acoustic communication device includes a computer device having an acoustic transmitter and/or an acoustic receiver. A signal processing module processes sound signals such that the transmitter and/or receiver are employed to permit acoustic communication between computer devices using sound signals.

1. Field of the Present Disclosure
The present disclosure relates computer communication, and more particularly to short range and peer-to-peer communication with computers using acoustic signals.
2. Description of the Related Art
Computer communication is obtained by converting digital data to a physical signal, and transmitting the signal over a channel, for example, infrared over air, radio frequency over air, light signal over fiber, electrical voltage over copper wire, etc. Depending on the properties of the signal and the channel, different properties and restrictions apply. For example, infrared and light signals are uni-directional and thus require a Line Of Sight (LOS) between the transmitter and the receiver.
Wireless radio communication does not typically require a line of sight between transmitter and receiver. However, wireless computer communication requires wireless transmitters and receivers along with associated antennae and other hardware in order to establish and maintain communication therebetween. Wireless communication further relies on radio frequency modulation and may be overkill for short-range communications.

Method and apparatus for computer communication using audio signals

International Business Machines Corporation


Compounds and methods for stimulating and enhancing immune responses and for evaluating patient immune responses are disclosed. Disclosed compounds include polypeptides that contain at least a biologically active portion of a Leishmania braziliensis homolog of the eukaryotic initiation factor 4A, or a variant thereof. Such compounds are useful for stimulating a Th1 immune response and IL-12 production in patients, as well as in isolated cells and cell cultures. The polypeptides of this invention are further useful for the evaluation and treatment of patients, who may be afflicted with leishmaniasis or other disorders.

Leishmania are obligate intracellular protozoan parasites of macrophages that cause a spectrum of human diseases, including self-healing skin lesions, diffuse cutaneous and mucosal manifestations, and severe visceral disease. The number of cases of leishmaniasis has increased dramatically in the last 20 years, with about 2 million new cases diagnosed each year. Millions of cases of the disease now exist worldwide, primarily in Brazil, China, East Africa, India and areas of the Middle East. The disease is also endemic in the Mediterranean region, including southern France, Italy, Greece, Spain, Portugal and North Africa.
There are 20 species of Leishmania that infect humans. Of these species, Leishmania braziliensis commonly causes localized cutaneous leishmaniasis (CL). Patients with CL have strong delayed-type hypersensitivity (DTH) and in vitro proliferative responses to Leishmania antigens during both active and cured disease. Most patients with CL heal spontaneously. However, in some infected individuals, an active cutaneous disease or mucosal leishmaniasis (ML) arises, which is characterized by severe and progressive destruction of the nasal, oral and/or pharyngeal mucous membranes.
Early diagnosis of leishmaniasis may be critical for successful treatment, but is difficult to achieve since there are no distinctive signs or symptoms of the disease. Parasite detection methods have been used, but such methods are not sensitive or practical. Current serological tests (using, for example, ELISA or immunofluorescence techniques) typically use whole or lysed parasites, and are generally insensitive and prone to cross-reaction with a variety of other diseases. In addition, such methods often fail to detect the potentially fatal disease early enough to allow effective treatment, since they rely on the detection of antibodies that are present during the acute phase of the disease.
In the case of active mucosal disease, the intradermal skin test and lymphocyte proliferative responses to Leishmania antigens are exceptionally strong. In fact, it is possible that tissue destruction associated with mucosal lesions may result in part from a hypersensitivity response to Leishmania antigens. However, the specific antigens involved in the cell-mediated immune response to Leishmania have not been characterized.
Accordingly, there is a need in the art for characterization of Leishmania antigens involved in immune responses, and a determination of their role in disease manifestation. There is also a need to identify improved methods for evaluating patients in the early stages of the disease and for treating leishmaniasis. The present invention fulfills these needs and further provides other related advantages.

Compounds and methods for the stimulation and enhancement of protective immune responses and IL-12 production


A stair making apparatus is disclosed. The stair making apparatus comprising a bench adapted to support a plurality of members and a beam; a stop fixture connected to the bench, the stop fixture having a plurality of stops for individually engaging each of the plurality of members; and one or more fasteners connected with the bench, the one or more fasteners configured to cooperate with the plurality of stops to brace the beam and the plurality of members in a form of a stair stringer.

1. Field of the Invention
The present invention relates generally to work benches. More specifically the present invention relates to a work bench for assembling stair stringers.
2. Discussion of the Related Art
A typical staircase is comprised of an alternating series of treads and risers that form the individual steps of the staircase. The treads, and in most cases the risers, are supported by a pair of stair stringers that form part of the staircase structure. Stair stringers are frequently constructed at a construction worksite where the staircase is to be constructed.
To construct a typical stair stringer, a carpenter will "layout" a stair stringer by marking a single 2×12, 2×14 or other sized piece of lumber with layout lines. The layout lines identify the contour or shape of the stair stringer. The shape of the stair stringer generally comprises an elongated beam with multiple triangular edges that support the individual treads and risers. The carpenter saws along the layout lines that define the triangular edges leaving a stair stringer. The carpenter will then usually dispose of the remaining pieces of lumber as waste.
A matching stair stinger is constructed similarly. The carpenter carefully marks a single piece of lumber with layout lines and saws a complementary stair stringer from the single piece of lumber. The carpenter typically disposes of the remaining lumber as waste. The stair stringer and the matching stair stringer are then installed parallel to each other. Treads and risers are attached to the pair of stair stringer forming a staircase.
It can be appreciated that the carpenter must carefully layout and saw the stair stringer and matching stair stringer to allow accurate placement of the treads and risers. It can also be appreciated that the task of cutting stair stringers from a single piece of lumber is a time consuming task; particularly, since most carpenters at a worksite spend a very small proportion of their time at this task. Moreover, lumber waste is an undesirable residue of this process.
Those skilled in the art will recognize that there is a need for an apparatus that allows a carpenter to: quickly, easily and accurately construct the stair stringers of a staircase with little lumber waste. It can also be appreciated that an apparatus that can be used to make stair stringers at a lumberyard would allow carpenters to specialize in constructing stair stringers, allowing mass production of stair stringers for multiple construction worksites. Applicant's invention addresses these needs as well as other needs.


A method and apparatus for evaluating a conditioned electrochemical mechanical polishing pad are provided. A polishing pad is conditioned using a first set of process conditions. A sheet wafer and a residue wafer are polished on the polishing pad. The removal rates of one or more materials from the sheet wafer and the residue wafer are measured. A normalized removal rate is calculated. The polishing pad is further conditioned if the normalized removal rate is not within a minimum value and a maximum value. In one embodiment, the normalized removal rate comprises a ratio of the removal rate of the residue wafer to the removal rate of the sheet wafer.

1. Field of the Invention
Embodiments of the present invention generally relate to a method and apparatus for conditioning a polishing pad.
2. Description of the Related Art
Electrochemical Mechanical Processing (ECMP) is a technique used to remove conductive materials from a substrate surface by electrochemical dissolution while concurrently polishing the substrate with reduced mechanical abrasion as compared to conventional Chemical Mechanical Polishing (CMP) processes. ECMP systems may generally be adapted for deposition of conductive material on the substrate by reversing the polarity of the bias applied between the substrate and an electrode. Electrochemical dissolution is performed by applying a bias between a cathode and a substrate surface to remove conductive materials from the substrate surface into a surrounding electrolyte. The bias may be applied to the substrate surface by a conductive contact disposed on or through a polishing material upon which the substrate is processed. The polishing material may be, for example, a processing pad disposed on a platen. The processing pad is an important aspect of the ECMP process. The processing pad must have the appropriate mechanical properties for substrate planarization while minimizing the generation of defects in the substrate during polishing. A mechanical component of the polishing process is performed by providing relative motion between the substrate and the polishing material that enhances the removal of the conductive material from the substrate.
ECMP normally comprises removal of bulk conductive material with a high removal rate, removal of a residual conductive material with a moderate removal rate, followed by removal of a barrier layer. Efficient removal of the conductive material depends upon uniform biasing of the conductive material. As a result, uniform local electrical contact between the polishing material and the substrate surface is highly desirable. For this reason, pad conditioning procedures (break-in procedures) and apparatus have been developed to condition pads so they can provide superior local electrical contact.
Therefore, there is a need for a method and apparatus for evaluating the ability of a conditioned polishing material to provide uniform local electrical contact to a substrate surface.

Method and apparatus for evaluating polishing pad conditioning


A new and distinct cultivar of Angelonia plant named ‘Balangdaros’ characterized by its rose-pink colored flowers with darker pink spots, medium-sized flowers, and moderately vigorous, upright growth habit.

The present invention relates to a new and distinct cultivar of Angelonia plant botanically known as Angelonia angustifolia and hereinafter referred to by the cultivar name 'Balangdaros'.
The new cultivar was developed by the inventor in a controlled breeding program during January 2003 at Arroyo Grande, Calif. The objective of the breeding program was the development of Angelonia cultivars with unique flower colors, continuous flowering and moderately vigorous, freely branching and upright, growth habit.
The female (seed) parent of the new cultivar was the proprietary Angelonia angustifolia breeding selection designated BFP-895, not patented, characterized by its large dark purple-colored flowers, dark green-colored foliage, medium vigor, and upright growth habit. The male (pollen) parent of the new cultivar was the proprietary Angelonia angustifolia breeding selection designated BFP-873, not patented, characterized by its dark purple-colored flowers, dark green-colored foliage, medium vigor, and upright growth habit. The new cultivar was discovered and selected by the inventor as a single flowering plant within the progeny of the above stated cross-pollination on September 2003 in a controlled environment at Arroyo Grande, Calif.
Asexual reproduction of the new cultivar by terminal stem cuttings since September 2003 at West Chicago, Ill. has demonstrated that the new cultivar reproduces true to type with all the characteristics, as herein described, firmly fixed and retained through successive generations of such asexual propagation.


A security image and method of forming said image is disclosed wherein a substrate having an image or indicia thereon is coated with a dilute solution of pigment flakes in an ink or paint. The flakes are subsequently aligned in a magnetic field and are fixed after the field is applied. Most or all of the flakes in a region are aligned so as to be partially upstanding wherein their faces are essentially parallel. Coating the image with flakes yields a latent image which can be clearly seen at a small range of predetermined angles.

The coating of a substrate with an ink or paint or other similar medium having alignable particles or flakes therein to form an image exhibiting optically-illusive effects is known. Many surfaces painted or printed with flat platelet-like particles show higher reflectance and brighter colors than surfaces coated with a paint or ink containing conventional pigments. Substrates painted or printed with color-shifting flaked pigments show change of color when viewed at different angles. Flaked pigments may contain a material that is magnetically sensitive, so as to be alignable or orientable in an applied magnetic field. Such particles can be manufactured from a combination of magnetic and non-magnetic materials and mixed with a paint or ink vehicle in the production of magnetic paints or inks. A feature of these products is the ability of the flakes to become oriented along the lines of an applied field inside of the layer of liquid paint or ink while substantially remaining in this position after drying or curing of the paint or ink vehicle. Relative orientation of the flake and its major dimension in respect to the coated surface determines the level of reflectance or its direction and, or may determine the chroma of the paint or ink. Alternatively, dielectric material may be alignable in an electric field.
Alignment of magnetic particles along lines of an applied magnetic field has been known for centuries and is described in basic physics textbooks. Such a description is found in a book by Halliday, Resnick, Walker, entitled, Fundamentals of physics. Sixth Edition, p. 662. It is also known to align dielectric particles in an electric field, and this form alignment is applicable to this invention.
The patents hereafter referred to are incorporated herein by reference for all purposes.
U.S. Pat. No. 3,853,676 in the name of Graves et al. describes painting of a substrate with a film comprising film-forming material and magnetically orientable pigment that is oriented in curved configurations and located in close proximity to the film, and that can be seen by the naked eye to provide awareness to the viewer of the location of the film.
U.S. Pat. No. 5,079,058 by Tomiyama discloses a patterned film forming a laminated sheet comprising a multi-layer construction prepared by successively laminating a release sheet layer, a pressure-sensitive adhesive layer, a base sheet layer, and a patterned film layer, or further laminating a pigmented print layer. The patterned film layer is prepared by a process which comprises coating a fluid coating composition containing a powdery magnetic material on one side of the base sheet layer to form a fluid film, and acting a magnetic force on the powdery magnetic material contained in the fluid film, in a fluid state, to form a pattern.
U.S. Pat. No. 5,364,689 in the name of Kashiwagi discloses a method and an apparatus for producing of a product having a magnetically formed pattern. The magnetically formed pattern becomes visible on the surface of the painted product as the light rays incident on the paint layer are reflected or absorbed differently by magnetic particles arranged in a shape corresponding to desired pattern. More particularly, Kashiwagi describes how various patterns, caused by magnetic alignment of nickel flakes, can be formed on the surface of a wheel cover.
U.S. Pat. No. 6,808,806 by Phillips in the name of Flex Products Inc., discloses methods and devices for producing images on coated articles. The methods generally include applying a layer of magnetizable pigment coating in liquid form on a substrate, with the magnetizable pigment coating containing a plurality of magnetic non-spherical particles or flakes. A magnetic field is subsequently applied to selected regions of the pigment coating while the coating is in liquid form, with the magnetic field altering the orientation of selected magnetic particles or flakes. Finally, the pigment coating is solidified, affixing the reoriented particles or flakes in a non-parallel position to the surface of the pigment coating to produce an image such as a three dimensional-like image on the surface of the coating. The pigment coating can contain various interference or non-interference magnetic particles or flakes, such as magnetic color shifting pigments.
U.S. Pat. No. 6,103,361 reveals patterned substrates useful in producing decorative cookware formed by coating a base with a mixture of fluoropolymer and magnetic flakes that magnetically induce an image in the polymer coating composition.
A common feature of the above-mentioned prior art references is a formation of one or more patterns in a painted or printed layer. Typically such patterns include indicia such as symbols, shapes, signs, or letters; and these patterns replicate the shape of a magnetic field often located beneath the substrate and are formed by shadowing contour lines appearing in the layer of paint or ink resulting in particular alignments of magnetic flakes. The desired pattern becomes visible on the surface of the painted product as the light rays incident on the paint layer are reflected or absorbed differently by the subgroup of magnetic non-spherical particles.
Although these prior art references provide some useful and interesting optical effects, there is a need for patterns which have a greater degree of optical illusivity, and which are more difficult to counterfeit. United States patent application number 20050106367, filed Dec. 22, 2004 in the name of Raksha et al. entitled Method and Apparatus for Orienting Magnetic Flakes describes several interesting embodiments which provide optical illusivity, such as a "flip-flop" which may serve as the basis of particular embodiments of this invention. Notwithstanding, there is need to provide different patterns on a single substrate wherein an image in the form or text or a logo, or identifiable feature is printed upon a substrate and wherein a coating of aligned flakes is disposed thereover rendering the image as a latent image that is highly visible when viewing at a first angle and barely visible or not visible at all when viewing the image from another angle.
In the past, attempts to make a hidden image in a security printing have been disclosed, for example in U.S. Pat. Nos. 3,640,009, 4,310,180, and 4,668,597.
A printed hidden image is described at the web site of Austria Card (a subsidiary of the Austrian Central Bank). Related information can be found at:
http://www.austriacard.at/main/EN/Products/IndustryAndGoverment/SecuritFeatures/index.html. The device described is produced by means of a halftone displacement of the hidden image. The printed hidden image is only visible with a special decoding lens.
Latent Filter Image (LFI®)_is manufactured by TRUB (http://www.trueb.ch/en/products/national/rohkarte.php). The LFI® is like a hidden image which has an integrated decoding filter. Tilting the card displays an inverted image.
Although this printed hidden image is interesting and appears to perform its intended function, it is quite complex and costly to produce and requires registration of a filter with a region supporting the printed hidden image.
It is an object of this invention to form a security device that has a latent image thereon that can be detected or seen at certain viewing angles and which is difficult to see at other angles. Complex instructions are not required to see the latent image. One only has to tilt the image from one direction to another to see the image appear or essentially disappear.

Printed magnetic ink overt security image


According to this invention, there is provided a molding method and apparatus which increase the gas permeation speed in obtaining a foamed resin molded product by letting a gas permeate a molten resin material. To achieve this object, a chip- or pellet-like resin material is evacuated and subjected to dehumidifying/drying processing, and replacement processing in an inert gas in a pre-processing unit, the resin material is then held in an inert gas of a predetermined temperature and pressure in an inert gas permeation unit for a predetermined period of time, the temperature and pressure are decreased, the material is fed to a material hopper whose temperature and pressure are controlled, the material is fed to a plasticizing unit to which a gas of a predetermined temperature and pressure is fed, the resin material is melted in the plasticizing unit, the resin material is injected/charged into a mold which is evacuated in advance to a pressure not more than atmospheric pressure, the pressure is restored to atmospheric pressure after the resin material is cooled for a predetermined period of time, and a foamed product is extracted by opening the mold.

The history concerning foam molding is old; a technique of obtaining a foamed product made of a resin by injection molding is disclosed in, for example, U.S. Pat. No. 3,268,639 and U.S. Pat. No. 3,384,691. Recently, foam molding methods using chemical foaming agents and physical foaming agents can be learnt from textbooks for synthetic resin molding and the like. As is known from styrofoam and the like, conventional foam molding exhibits a very high foaming magnification, and hence has an advantage in terms of weight reduction but suffers low mechanical strength. In addition, many problems are posed in the use of chemical foaming agents in terms of toxicity, mold corrosion, molding environment degradation, difficulty in handling, and the like. In contrast to this, a foam is disclosed in U.S. Pat. No. 3,796,779, which is obtained by directly blowing an inert gas, e.g., carbon dioxide gas, into a molten resin material, letting the gas permeate the resin, and then cooling the resin. The use of an inert gas as a foaming agent solves the problems of toxicity, mold corrosion, molding environment degradation, difficulty in handling, and the like. According to U.S. Pat. No. 3,796,779, however, since the gas is directly blown into the molten resin, the resin and gas are not uniformly mixed to form island structures in various cell shapes. For example, the resultant structure partly decreases in strength. That is, it is very difficult to control a foamed state. To eliminate these drawbacks, a method of molding very small foams called microcells was invented in Massachusetts Institute of Technology in the U.S. early in the 1980s. This method and apparatus are disclosed in U.S. Pat. No. 4,473,665, U.S. Pat. No. 5,158,986, U.S. Pat. No. 5,160,674, U.S. Pat. No. 5,334,356, U.S. Pat. No. 5,571,848, and U.S. Pat. No. 5,866,053. According to the method and apparatus developed Massachusetts Institute of Technology, a supercritical inert gas is blown into a portion of the plasticizing unit of an injection molding machine in which a resin is molten, and the molten resin and gas are sufficiently mixed by a static mixer, while pressure and temperature control is performed. In the resultant foamed product, many small cells with sizes of 25 μm or less are uniformly dispersed. Since the cell diameters are small, a molded product that is almost free from a decrease in strength can be obtained. In addition, the following method is known. When a resin is to be injected into a mold, the mold is filled with a gas and pressurized with atmospheric pressure or more in advance, and the resin is injected. After the resin is completely charged into the mold, the gas pressure is released to cause gas foaming in the resin.
In the conventional method, since a gas is directly blown into a molten resin material, a molten resin portion that comes into contact with the gas is rapidly cooled when the gas is blown. If the gas is continuously blown into the resin, the molten resin is mostly cooled. As a consequence, the viscosity of the resin increases, and it takes much time to restore the resin temperature and viscosity that are suited to molding. In addition, when a gas is to be heated to a temperature near the melting temperature of the resin in advance, the volume of the gas increases with a rise in temperature. If, therefore, the gas is directly blown into the molten resin, since the gas pressure in the resin is low, the foaming magnification after the charge of the resin into the mold is excessively low. A method of compensating for this drawback is available, in which the temperature and pressure of a gas are raised to maintain the gas concentration, and the gas is then blown into a molten resin. In this case, however, the pressure of the gas is very high, and hence flows into a molten resin as soon as it is blown thereinto. This makes it difficult to control the amount of gas blown. In addition, since the gas is quickly blown into the molten resin, the resin into which the gas is blown is formed into a two-isolated-layer structure. To uniformly disperse the gas into the resin, the gas and resin must be repeatedly kneaded mechanically by a static mixer or the like. This complicates the apparatus and prolongs the cycle, resulting in a deterioration in productivity. The plasticizing unit of an injection molding machine or extrusion machine is configured to apply a certain pressure to a molten resin to purge air from a material or a material during metering. If, therefore, a gas is blown into a molten resin and metered as in the prior art, the gas is discharged to the metering portion side of the plasticizing unit before the blown gas completely dissolves in the resin. According to the method of filling a mold with a gas, applying a pressure equal to atmospheric pressure or more in injecting a resin into a mold, and then releasing the gas pressure after the resin is charged, if the filling speed is high, the pressure of the gas charged into the mold cannot be controlled. As a result, the charge gas causes a short shot. If the filling speed of a resin is decreased, the gas charged into the mold can be controlled, and the pressure of the gas during and after the charge of a resin can be controlled. Owing to the low filling speed, however, a large skin layer is formed, which solidifies when it comes into contact with the mold as the mold is cooled. For this reason, in the foaming distribution of the molded product, the foaming differences between the surface and the central portion in the direction of thickness and between a portion near the gate and the finally filled portion become vary large.
A technique associated with an audio equipment structure is disclosed in, for example, Japanese Patent Publication No. 60-47796.
The technique disclosed in this reference is associated with a structural member having a three-layer structure formed by a surface layer and core layer, which is formed by injection molding.
The technique disclosed in this reference is a technique of taking measures against the mechanical and audio vibration sources of audio equipment or vibrations from other sources.
As a technique of preventing resonance, a technique using a sandwich structure is disclosed in Japanese Patent Publication No. 52-28657.
When a resin molded product molded by a resin material is to be used as the above audio equipment or the housing structural member of video equipment, a foam molding technique is available as a technique for a reduction in the weight of the structural member and the problem of sinkmarks formed on in a resin surface which is unique to resin molding. This technique is disclosed in, for example, U.S. Pat. No. 4,473,665, U.S. Pat. No. 4,360,484, and Japanese Patent Laid-Open Nos. 8-300392 and 10-24436.
In image forming apparatuses such as electrophotographic copying machines, laser beam printers, and facsimile apparatuses, other office equipment, industrial equipment, and the like, vibrations from vibration sources such as rotating members like motors and vibration generating members adversely affect the image forming step, and adverse effects on the information transmission step adversely affect image and information output results.
Information equipment such as a computer incorporates a cooling fan motor as a countermeasure against heat dissipation from electric and electronic elements.
In printers, particularly, laser printers which have remarkably become popular in the recent years owing to an increase in image resolution, the vibrations produced by motors for rotating/driving polygon mirrors greatly influence the resolution of images in apparatuses for transferring image information created by laser scanning to image carriers such as paper through information transfer means such as polygon mirrors, optical lenses, and the like.
The above parts and units such as a motor, optical lens, and laser source are held and incorporated on a mount member in an image forming apparatus.
In the prior art, the mount member is a metal member or a molded product made of a resin material. For example, according to the technique disclosed in Japanese Patent Laid-Open No. 7-232358, to position the respective parts to be held on the mount member, projections are formed on the flat surface of the mount member to specify the positions of the parts, and a resin material used for the projections is compressed to guarantee the dimensional precision of the respective projections.
As the above office equipment and information equipment are widely used as terminals in offices and homes, the personal use of equipment have proliferated. As a consequence, demands have arisen for reductions in weight and cost as well as size.
The mount member is preferably a molded product made of a resin material to fix/place the above motor, laser source, polygon mirror, optical lens, and the like at predetermined positions of the respective parts.
If a molded product made of a resin material is to be used as a mount member, consideration should be given to a reduction in weight. As a technique of reducing the weight of a resin molded member, a molding method of foaming a resin material is disclosed in U.S. Pat. 4,360,484, U.S. Pat. No. 4,473,665 and Japanese Patent Laid-Open No. 8-300392.
In addition, techniques associated with a product molded by foaming a resin material are disclosed in Japanese Patent Laid-Open Nos. 10-24436, 09-48039, and 12-25066.


An oxidation catalyst unit for a wet-type electrophotographic image forming apparatus which oxidizes a carrier vapor generated in a fusing unit and method for controlling the same are provided. The wet-type electrophotographic image forming apparatus includes a photoconductive medium, a laser scanning unit scans a laser beam onto the photoconductive medium, a developing unit develops a developer on the photoconductive medium, a transfer unit transfers the developer on the photoconductive medium to a recording medium, a fusing unit fixes the developer on the recording medium, and an oxidation catalyst unit oxidizes and resolves a carrier vapor generated in the fusing unit. The oxidation catalyst unit comprises a duct connected to the fusing unit to guide the carrier vapor generated in the fusing unit into the oxidation catalyst unit, a fan for guiding the carrier vapor into the duct, and a controller for varying a velocity of the fan according to data.

1. Field of the Invention
The present invention generally relates to an oxidation catalyst unit for a wet-type electrophotographic printer. More particularly, the present invention relates to an oxidation catalyst unit for oxidizing and thereby removing a carrier vapor generated in a fusing unit, a method for controlling the oxidation catalyst unit, and a wet-type electrophotographic image forming apparatus having the oxidation catalyst unit.
2. Description of the Related Art
An electrophotographic image forming apparatus scans a laser beam onto a photoconductive medium to form an electrostatic latent image, and transfers a visible image formed by attaching a developer onto the electrostatic latent image, thereby printing out a desired image. A wet-type electrophotographic image forming apparatus uses a liquid developer while a dry-type one uses a powder toner. The wet-type electrophotographic image forming apparatus produces a clearer image and high-quality color images can be obtained.
The developers consist of a toner and a liquid carrier, such as norpar. Norpar is a hydrocarbon-based solvent, which is a mixture of C10H22, C11H24, C12H26, and C13H28.
A paper onto which the developer is transferred passes through a fusing unit during which the toner component in the developer is fixed onto paper. When fused, liquid carrier, such as norpar, in the developer is vaporized by high temperature and discharged outward in the form of a hydrocarbon gas such as CH4.
The hydrocarbon gas is a volatile organic compound (VOC), which emits an offensive odor when discharged. Therefore, various methods for removing hydrocarbon gas have been introduced.
Conventional methods for removing hydrocarbon gases include the filtration, direct combustion, and catalytic oxidation methods. The filtration method physically removes gaseous components using a carbon filter, such as an active carbon filter. The direct combustion method combusts gaseous components at an ignition point of approximately 600° C. to 800° C. The catalytic oxidation method combusts gaseous components at a relatively lower temperature of approximately 150° C. to 400° C. using a catalyst, thereby oxidizing and resolving the components into water and carbon dioxide.
In the filtration method, the carbon filter does not have the capability of resolving the entrained carrier vapors. Therefore, the carbon filter becomes saturated with carrier vapors and needs to be replaced when the carrier vapors are entrained over a predetermined amount in the carbon filter, and such replacement needs to be done frequently. Furthermore, the direct combustion method is not safe due to the high temperature generated. Due to above the problems, the wet-type electrophotographic image forming apparatuses have mainly employed the catalytic oxidation method for removing the carrier vapors.
FIG. 1 is a schematic view of a conventional oxidation catalyst unit. The oxidation catalyst unit 160 comprises a duct 161, a suction fan 162, a heater 163, an oxidation catalyst carrying medium 164, and a controller 165. The controller 165 comprises a driving part 165a for driving the suction fan 162 and a power part 165b for supplying electric power to the driving part 165a.
The duct 161, which is connected to one side of a fusing unit 150, guides the carrier vapor V into the oxidation catalyst unit 160 to remove the carrier vapor V produced in the fusing unit 150. This occurs when paper P moves through the fusing rollers 151 and 152.
The suction fan 162 is mounted in the duct 161 to forcibly send the carrier vapor V toward the oxidation catalyst carrying medium 164.
The heater 163 raises the temperature of the carrier vapor V to an activating temperature, for example, 200° C. The oxidation catalyst carrying medium 164 carries a catalyst such as Pt and Pd, which catalyzes the oxidization reaction. The oxidation catalyst carrying medium 164 is mounted behind the heater 163.
The suction fan 162 of the conventional oxidation catalyst unit 160, which draws in the carrier vapor V, rotates at a uniform velocity. The velocity of the suction fan 162 is determined or set based on the maximum amount of carrier vapor V. The maximum amount of carrier vapor V is mainly caused when printing a whole-color image.
FIG. 2 is a graph illustrating the fan velocity of the oxidation catalyst unit 160 of FIG. 1 according to the amount of image data. Referring to FIG. 2, whether printing a text image, which causes a relatively small amount of the carrier vapor V (FIG. 1), or a whole-color image, which causes a relatively larger amount of the carrier vapor V (FIG. 1), the suction fan 162 (FIG. 1) operates at the maximum velocity N. Therefore, the suction fan 162 (FIG. 1) is constantly applied with a load regardless of the amount of image data, and accordingly, the noise and vibration of the suction fan 162 increases due to the overload. In addition, power is wasted.
The above problems also occur when the temperature of the heater 163 in the oxidation catalyst unit 160 is set corresponding to the maximum amount of the carrier vapor V without regard to the actual amount of the carrier vapor V, or when the velocity of a cooling fan (not shown) of the image forming apparatus is always set corresponding to the maximum amount of the carrier vapor V without regard to the actual amount of the carrier vapor V.
Accordingly, there is a need for an oxidation catalyst unit wherein the heater temperature or the cooling fan velocity is set corresponding to the actual amount of carrier vapor V.

Oxidation catalyst unit, a controlling method thereof, and a wet-type electrophotographic image forming apparatus comprising the oxidation catalyst unit