The present invention relates to an antibody or antibody fragment that binds to 1,4,7,10-tetrazacyclododecane-N,N′,N″,N′″-tetraacetic acid (DOTA),which is bound to an alkyl-amino group through one of its pendant carb.oxyl groups.

1. Field of the Invention
The present invention relates to an antibody or antibody fragment that binds to 1,4,7,10-tetrazacyclododecane-N,N′,N″,N′″-tetraacetic acid (DOTA),which is bound to an alkyl-amino group through one of its pendant carboxyl groups.
2. Related Art
Multi-specific antibodies (msAbs) offer the possibility of improved efficacy in the delivery of radionuclides using antibody targeting. Radionuclide therapy can be more efficacious when the radionuclide is attached to a moiety that is bivalent toward the pretargeted msAb. For example, cross-linking of pretargeted msAb localized at the disease target was effected by a bivalent hapten moiety that carried the radiolabel (Barbet, U.S. Pat. No. 5,256,395). This approach was used for radioimmunotherapy (RAIT) using the radionuclide iodine-131, which had been attached to a suitable bivalent hapten. The recognition system of the second arm of the msAb used in these studies was based on an indium complex of the chelate diethylenetriaminepentaacetic acid (DTPA), which had been doubly attached to a peptide [tyrosyl-lysine], which could be radioiodinated at its tyrosine residue. Ironically, the DTPA-Tyr.Lys(DTPA).OH, although based on and containing chelating agents, was not useful for any radiometals other than indium, since the action of metal binding by metals other than indium effectively destroyed the affinity of the di-DTPA peptide for the recognizing arm of the msAb. To overcome this deficiency, other series of antibodies were raised that did not depend on recognition of a metal complex (Barbet, U.S. Pat. No. 5,274,076). While the reagents made were designed to be hydrophilic in nature, it was mandatory that a chelating agent would also need to be appended to the recognition unit, via a backbone structure of some kind, and this certainly further complicated preparative procedures. In addition, each increase in size of the bivalent hapten could result in a poorer, incomplete clearance pattern in vivo, destroying one of the major advantages of the system based on the DTPA-Tyr.Lys(DTPA).OH recognition peptide.
Known antibodies directed towards other chelating agents are not versatile in recognizing different metal-chelator complexes, nor do they possess high binding affinities to any metal-chelator complex. Antibodies to yttrium-DOTA have been previously prepared using a 2-benzyl-DOTA (a ring-carbon derivatized chelating agent) derivative linked to keyhole limpet hemocyanin (KLH) as immunogen. Several mAbs were described, all of which were IgG1 heavy chain and kappa light chain, with the exception of one that was IgG3 heavy chain and lambda light chain. These anti-DOTA antibodies all had a relatively low affinity (≅2×10−8M), which may not be optimal for use in a pretargeting approach. The mAb selected as best for further study (IgG1 and kappa) was found to bind equally well to both Gd-DOTA and to Y-DOTA, but much less well to other metal complexes such as In-DOTA, Cu-DOTA and Fe-DOTA. The authors ascribed this to the fact that the Y- and Gd-complexes were 9-coordinate [including one water molecule] whereas complexes with In-, Fe- and Cu- were 8-7- and 6-coordinate, respectively. The best binding metals were thought to be best due to the fact that the DOTA ring immunogen has all four amino and all four carboxyl groups available for metal binding, resulting in a higher denticity complex. Metals forming complexes with DOTA of lower denticity did not bind as well to the anti-DOTA-yttrium mAb.
Tissue specificity can be provided by monoclonal antibodies and peptides that target disease-associated antigens and receptors, respectively. However, direct binding of nuclides to these targeting agents often results in agents that have poor biodistribution characteristics, and therefore poor imaging and therapy qualities.
Thus a continuing need exists for a universal antibody directed towards a variety of chelator-metal complexes. The universal antibody will allow the skilled artisan the flexibility of using a single antibody for recognizing and maximizing uptakes of diagnostic and therapeutic nuclides and radionuclides, specifically in high amounts at diseased tissue, compared to surrounding normal tissues. Maximization of radioactivity in this manner can be expected to drastically improve imaging quality during diagnostic techniques and therapeutic ratios during therapy procedures.


The present application discloses a battery equalization system, a vehicle, a battery equalization method, and a storage medium. The battery equalization system includes: a collection circuit; an equalization circuit; a controller; a charging branch circuit, connected to a charging device and a battery pack; and a first power supply branch circuit, connected to the charging device and the battery equalization system, and configured to supply power to the battery equalization system. When a state-of-charge of the battery pack is full and a cell in the battery pack needs enabling of equalization, the controller controls the charging branch circuit to disconnect, and controls the first power supply branch circuit to keep connected, so that an equalization module performs equalization processing on the cell that needs enabling of equalization.

A battery pack is an important part of an electric vehicle. A battery pack is multiple cells connected in series. While a battery is in use, the difference between the cells in the battery pack gradually increases, resulting in poor consistency between the battery cells. Due to the short stave effect of the battery, the capacity of a battery pack cannot be brought into full play, thereby decreasing the overall capacity of the battery pack. Therefore, managing equalization of the battery pack of an electric vehicle effectively is helpful to improve the consistency between the cells in the battery pack, reduce the capacity loss of the battery, and extend the battery life and the mileage of the electric vehicle, and is of great significance.
In the practical application of related equalization technologies, main operations in a battery charging and discharging process are to collect battery information, determine whether equalization needs to be enabled for the battery and whether equalization processing needs to be performed for the battery, in which equalization efficiency is low and equalization time is long.

Battery equalization system, vehicle, battery equalization method and storage medium


A method for terminating defrosting of an evaporator (104) is disclosed. The evaporator (104) is part of a vapour compression system (100). The vapour compression system (100) further comprises a compressor unit (101), a heat rejecting heat exchanger (102), and an expansion device (103). The compressor unit (101), the heat rejecting heat exchanger (102), the expansion device (103) and the evaporator (104) are arranged in a refrigerant path, and an air flow is flowing across the evaporator (104). When ice is accumulated on the evaporator (104), the vapour compression system (100) operates in a defrosting mode. At least one temperature sensor (305) monitors a temperature Tair, of air leaving the evaporator (104). A rate of change of Tair is monitored and defrosting is terminated when the rate of change of the temperature, Tair, approaches zero.

Vapour compression systems, such as refrigeration systems, heat pumps or air condition systems, are normally controlled in order to provide a required cooling or heating capacity in an as energy efficient manner as possible. In some scenarios, the operation of the vapour compression system may become energy inefficient, and the system may even become unstable or the system may become unable to provide the required cooling or heating capacity. In particular, during operation of a vapour compression system, such as a refrigeration system with a cooled chamber, ice or frost will deposit on the heat transfer surfaces of an evaporator. Namely, condensation of moisture in the cooled chamber leads to ice accumulation over time on the evaporator in the refrigeration system. Ice buildups disturb air circulation inside the system. This leads to a decrease in cooling efficiency and hence negatively impacts the heat transfer performance. Frost and ice buildups must be recognized before the cooling efficiency of the system has been significantly reduced. Once frost and ice has been identified, defrosting will be initiated and ice will start melting. During defrosting, the evaporator is heated in order to melt ice buildups. It is desired that this defrosting mode lasts as short as possible for a number of reasons. One of the reasons is again energy efficiency and energy consumption. Additionally, it is desired that items comprised in the cooled chamber are cooled almost all times. Therefore, in the most optimal case, defrosting should be terminated as soon as all the ice and frost has been melted.
In commercial refrigeration systems, termination of defrosting is typically performed after a predetermined period of time upon defrosting initiation. In one example, this predetermined period of time may not be sufficient for complete defrosting to happen and the system may have remaining ice on the evaporator. In another example, the predetermined period of time may be longer than what is needed for complete defrosting to happen and in such a case, the system is not under optimal conditions for a too long period of time as defrosting consumes excessive energy. In yet another example, the system may be programmed to terminate defrosting when a certain temperature inside the evaporator is achieved. This approach may as well not be the most optimal in terms of complete defrosting of the evaporator as some parts of it may still have remaining ice. Remaining ice influences operation of the system and degrades performances which should be at a high level right upon defrosting. Furthermore, the remaining ice may speed up accumulation of new ice layers.
US 2012/0042667 discloses an apparatus and method for terminating a refrigeration unit's defrost function. The refrigeration unit comprises an evaporator, a temperature sensor to measure the temperature of the evaporator during a defrost function, and a controller configured to calculate the rate of temperature change and terminate the defrost function when the rate meets a specified criteria, such as a predetermined rate or a sharp increase in the rate after the evaporator temperature has increased above the freezing point of water.

Method for terminating defrosting of an evaporator by use of air temperature measurements


A connector structure, having a short-circuiting member, includes a housing, terminal receiving chambers formed in the housing, a short-circuiting member receiving chamber communicating with the terminal receiving chambers, the short-circuiting member having resilient contact plate portions formed thereon, the short-circuiting member being received in the short-circuiting member receiving chamber, so that the contact plate portions project respectively into the terminal receiving chambers to be press-contacted respectively with terminals mounted respectively in the terminal receiving chambers, and a contact plate portion urging unit urging the contact plate portions against a resilient force thereof to thereby limit an amount of projection of the contact plate portions into the terminal receiving chambers to a predetermined value.

This invention relates to a connector structure having a short-circuiting member for removing a potential difference between terminals.
In a circuit in which a load and a power source are connected together by a connector, an electric current may be induced in a load-side circuit by electromagnetic waves and static electricity when the connector is not in a connected condition. In this case, due to the difference in current intensity between signal lines, there is a possibility that a voltage develops between the signal lines, so that an equipment (load) is subjected to a malfunction. For example, in an air bag circuit in which an ignition signal is fed to an ignition device so as to inflate an air bag, such a situation should be avoided by all means so as to secure safety during the travel.
A connector structure, having a short-circuiting member for removing a potential difference between terminals, will be described with reference to FIGS. 8 to 10 (the connector structure shown in FIGS. 8-12 are not prior art for the present application). FIG. 8 is a cross-sectional view of the connector structure having the short-circuiting member, FIG. 9 is an exploded, perspective view of an important portion of the connector structure, and FIG. 10 is a cross-sectional view showing a condition in which terminals and an insulating plate of a mating connector are inserted into the connector of FIG. 8.
Terminal receiving chambers 3 are formed in a housing 1, and are open at one end thereof to a front surface of the housing 1 to form connection ports 5 for receiving the mating terminals, and are also open at the other end thereof to a rear surface of the housing 1 to form mounting ports 9 for receiving terminals 7. An elastic retaining piece portion 11 is provided in the terminal receiving chamber 3, and is retainingly engaged in an engagement hole 13, formed in the terminal 7, to retain the terminal against withdrawal. The terminals 7 are connected, for example, to an air bag ignition device (load).
A short-circuiting member 15, made of an electrically-conductive metal sheet, is mounted below the terminal receiving chambers 3 (that is, at a lower portion in FIG. 8). As shown in FIG. 9, the short-circuiting member 15 has a pair of contact plate portions 17 and 17. The contact plate portions 17 and 17 project respectively into the juxtaposed terminal receiving chambers 3 provided in the housing 1. Each of the contact plate portions 17 and 17 has a mountain-like shape having a peak at its central portion, and has front and rear slanting surfaces 19a and 19b.
The short-circuiting member 15 is attached to the housing 1 before mounting the terminals 7. When each terminal 7 is inserted into the associated terminal receiving chamber 3, the terminal 7 first abuts at its distal end against the slanting surface 19b, and forces the contact plate portion 17 out of the terminal receiving chamber 3, so that the contact plate portion 17 is held in press-contact with the terminal 7, as shown in FIG. 8.
Therefore, the pair of terminals 7 and 7, received respectively in the pair of terminal receiving chambers 3, are electrically connected together by the short-circuiting member 15, thereby removing a potential difference between the terminals in a non-connected condition of the connector. As shown in FIG. 10, the mating connector, connected to a power source, includes projecting terminals 21 and an insulating plate 23, and when the two connectors are connected together, the insulating plate 23 is inserted between the pair of terminals 7 and 7 and the pair of contact plate portions 17 and 17.
In the above connector structure related to the present invention, the terminals 7 and 7 are connected to a power source-side circuit when the two connectors are connected together, and when the two connectors are not connected together, the terminals 7 and 7 are short-circuited together, thereby removing a potential difference therebetween, thus positively preventing a malfunction of the electronic circuit.
In the above related connector structure, however, the contact plate portions 17 of the short-circuiting member 15 project far into the respective terminal receiving chambers 3 as shown in FIGS. 11 and 12 so that they can contact the respective terminals 7 with a sufficient contact pressure, and therefore when the terminal 7 is inserted, the distal end of the terminal 7 sometimes fails to properly abut against the slanting surface 19b of the contact plate portion 17 as shown in FIG. 11, and forces the contact plate portion 17 upward, which leads to a possibility that the terminal 7 or the contact plate portion 17 is damaged. To avoid this, if the amount of projection of the contact plate portion 17 into the terminal receiving chamber 3 is reduced, the load (or pressure) of contact of the contact plate portion 17 with the terminal 7 is reduced, which causes the increase of a resistance or the incomplete contact.


Various embodiments of a modular signage system having a modular post that enables placement and display of a plurality of signs. The modular post includes a tab chamber that engages one or more signs and is configured to engage a stake for embedding within a ground surface.

The purpose of real-estate and event markers is to present information to a potential attendee or customer in a manner that is striking without being distracting and with clear visuals displaying pertinent information. However, typical real-estate and event markers come in fixed or limited configurations and can also be cumbersome to transport, assemble, and install. In addition, organizations such as schools or event venues that wish to promote products or provide directions or general information in a modular and easy-to-read format often have to create their own content or purchase new signs for specific applications.
It is with these observations in mind, among others, that various aspects of the present disclosure were conceived and developed.
Corresponding reference characters indicate corresponding elements among the view of the drawings. The headings used in the figures do not limit the scope of the claims.

Systems and methods for a modular signage system


The present invention relates to a cellulose acylate film having a high modulus of elasticity and a high surface hardness. The cellulose acylate film of the present invention is characterized by containing 1 vol % to 99 vol % of a metal oxide having an average particle size of 1 nm to 400 nm. The metal oxide used here is preferably a metal oxide having a Mohs hardness of at least 7, and specific examples thereof include aluminum oxide and silicon dioxide. This metal oxide may be subjected to a surface treatment. Furthermore, a functional thin film such as a hardcoat layer may be formed on the cellulose acylate film containing the metal oxide.

Cellulose acylate films are widely used in optical applications such as protection films for polarizing plates since they can be easily produced in the form of films that have excellent transparency and low refractive index an isotropy.
Accompanying increases in the range of applications of liquid crystal display devices and the places they are used, there is an increasing demand for the protection film surface to have high mechanical strength in order to prevent damage to the display screen.
However, cellulose acylate films have the drawbacks of a small modulus of elasticity and a low surface hardness in comparison with polyester films, which are often used as protection films, etc.

Cellulose acylate film, cellulose acylate film with functional thin film, and method for preparation thereof


Techniques for duplicate code section detection for source code are described herein. An aspect includes receiving a plurality of input files corresponding to a software project comprising source code written in a computer programming language. Another aspect includes segmenting each of the plurality of input files into a plurality of statements based on instruction boundaries corresponding to the computer programming language, wherein a respective statement start index is determined for each of the plurality of statements. Another aspect includes populating an enhanced generalized suffix array (eGSA) based on the determined statement start indices, wherein each statement start index corresponds to a respective suffix in a row in the eGSA, and wherein each row comprises a longest common prefix (LCP) field and a preceding statement value corresponding to the row's respective suffix. Another aspect includes identifying duplicate code sections in the plurality of input files based on the eGSA.

The present invention generally relates to computer systems, and more specifically, to duplicate code section detection for source code in a computer system.
A software project may include a large number of files, each containing many lines of source code. When programming for a large software project, programmers may reuse, or duplicate, the same or similar logic at multiple locations or contexts within the software project. Duplicate code sections may create potential maintenance issues in the software project and may also create liability issues due to copyright ownership of the original code.

Duplicate code section detection for source code

INTERNATIONAL BUSINESS MACHINES CORPORATION


A display drive device comprises a display element being colored by injecting an electric charge into an electrolyte via an display electrode due to an oxidation-deoxidization reaction and being decolored by injecting an electric charge having an inverse polarity of the electric charge into the electrolyte, at least one constant current supply circuit which supplies a constant current as a decoloration current pulse having a predetermined pulse width to the display electrode upon the decoloration, a voltage detection circuit which detects a voltage value generated in the display electrode, and a control circuit which controls an operation of the constant current supply circuit intermittently and repeatedly supplying the decoloration current pulse from the constant current supply circuit to the display electrode upon the decoloration, and ending the decoloration on the basis of a voltage value to be detected by the voltage detection circuit.

1. Field of the Invention
The present invention relates to a display drive device for driving a display unit having an electrochromic element and a display device provided with the same.
2. Description of the Related Art
There have been proposed various display devices having a display unit provided with a display element (namely, an electrochromic element) using a phenomenon such that a solute in an electrolyte separates out or dissolve due to an oxidation-deoxidization reaction by injecting an electric charge in the electrolyte. For example, in the case of the display device using bismuth (Bi) as a main material, when a negative electric charge is injected from a transparent electrode such as an indium tin oxide (ITO), a Bi ion in the electrolyte is deoxidized to separate out on the transparent electrode and this part is colored black. On the contrary, when a positive charge is injected from the transparent electrode into the electrolyte, Bi which has separated out on the transparent electrode is oxidized to solve into the electrolyte and this part is decolored.
In this type of display device, the amount of the solute to separate out is determined depending on the amount of the electric charge injected into the electrolyte, so that the larger the area of the display unit is, the more the amount of the solute should be increased by injecting more electric charges into the electrolyte.
In order to inject the electric charge according to the area of the display unit in this way, conventionally, the electric charge is injected by supplying a constant voltage for a predetermined time. In the case of driving the display unit by supplying the constant voltage from the display drive device for driving the display unit to the display unit, it has been known that a resistance value of the display unit at the time of coloration is in inverse proportion to the display area if a wiring resistance up to the display unit can be ignored. In addition, it has been known that the resistance value is in inverse proportion to the display area also at the time of decoloration until the decoloration is completed, as well as at the time of coloration. As a result, when the constant voltage is supplied from the display drive device for a predetermined time, it is possible to inject the electric charge of the amount which is approximately in proportion to the display area.
However, a method for simply supplying a predetermined amount of voltage waveform involves a problem that it is difficult to keep a balance between the amount of the solute to separate out and the amount of the solute to be dissolved, and an operating life is short. In other words, if coloration and decoloration are repeated many times, the balance between the amount of the solute to separate out and the amount of the solute to be dissolved is deteriorated, and this easily causes a defect where a part of the colored portion does not decolor due to excessive deposition and the electrolyte may change colors due to generation of other substance (for example, an iodine) in the electrolyte because dissolution of the solute has been progressed too much. Particularly, if time from a coloration step to a decoloration step is made longer, the decoloration may naturally occur and this easily generates excessive decoloration.
In the case of decoloration, differently from coloration, when the decoloration has progressed to some degrees, it has been known that the resistance value is changed and a current is decreased. In order to compensate decrease of the amount of the electric charge due to decrease of the current, the voltage in the case of the decoloration should be higher than that in the case of coloration or the voltage supplying time should be longer, because the amount of the electric charge necessary for decoloration is equivalent to that necessary for coloration. In this case, a voltage drop is generated due to a wiring resistance between the display unit and the display drive device and a contact resistance between the circuits or the like and the flowing current is largely changed, so that it is necessary to control the supplied voltage and the supplying time in consideration of these effects. However, the value of the wire resistance and the value of the contact resistance between the circuits generally vary widely and it is not easy to make these values constant.


An ocean thermal energy conversion assembly includes a ship having support tubes connected between a lower part and a top deck of the ship so as to define an open space. A passage is defined through the lower part and an annular connector is connected to a lower end of the passage. A plurality of rods extend from a top of the annular connector and are pivotably connected to the annular connection portion. A transmission pipe is connected to an underside of the annular connector. A hollow damper is connected to an outer periphery of the annular connector and an outer periphery of the hollow damper is engaged with an inner periphery of a bottom opening in a lower end of the passage. A top cover seals a top opening of the passage and has a wave-elimination way which communicates with holes in the top cover.

An ocean thermal energy conversion system employs the difference of temperature of sea water to generate electric power. Generally speaking, the temperature of the sea water at the deeper is lower than that close to the surface and the difference can be 20° C. It requires a significant amount of sea water to generate business scale of electric power, a huge pipe and ship are basic for establishing an ocean thermal energy conversion assembly. However, the connection between the ship and the pipes have to be secure enough to bear the force applied thereto from the waves. Generally, the pipes are fixed to the ship by a hard way which means there is limited flexibility of the connection so that when the waves hit the ship and the pipes, or the sea streams apply a force to the connection, the pipes are easily damaged and the connection can be easily broken. Once there is a leakage at the connection, the pipes are dragged and separated from the ship.
The present invention intends to provide a wave elimination system for reducing impact to the connection between pipes and ocean thermal energy conversion assembly, the ship used in the system includes an open space defined between the deck and the lower part of the ship, the sea level is on the half height of the open space so that the waves cannot apply too much force to the ship such that the impact from the waves is reduced.

Wave elimination system for ocean thermal energy conversion assembly


Methods, systems and apparatus, including computer program products, for anti-aliased rendering. A plurality of objects is received. Each object in the plurality of objects is depth-ordered. Each object is rendered from back to front into a plurality of pixels. Each pixel in the plurality of pixels has a respective color value. The rendering includes selecting an object from the plurality of objects. Respective alpha values are determined for first pixels in the plurality of pixels based on coverage of the first pixels by the selected object. The respective color value of each of the first pixels is attenuated based on the respective alpha values. The respective color value of each of the first pixels is added to based on the respective alpha values and one or more color properties associated with the selected object.

The present disclosure relates to anti-aliased rendering of objects.
Modern graphics processing engines that are used to render a set of primitives typically have a mode in which anti-aliasing is performed during rendering of the primitives.
Anti-aliasing, sometimes called anti-aliased rendering, is achieved by allocating N color buffers and rendering each primitive N times to the buffers. For any particular pixel, the N color values of the pixel specified in the N buffers represent N samples derived by rendering the set of primitives. To produce the anti-aliased image, where each pixel has a single color value, the N buffers are averaged together. This technique works well but requires a lot of memory, particularly when the desired number of samples is large. Since each buffer is completely rendered, the technique also demands significant memory bandwidth.
Alternatively, a buffer of size S×N may be used, where S is the size of the desired image. Using this buffer, N neighboring pixels (organized in a square pattern and therefore applicable when N is a power of two) correspond to a single pixel in the desired image. The scene is rendered once into this large buffer, where each object in the scene covers N times as many pixels as it would in the desired image. Every N pixels of the large buffer are averaged to obtain one anti-aliased pixel in the desired image. Using this technique, the required memory is also (N+1)×S, the buffer itself, plus another buffer for the desired image.


A localizing apparatus includes a frame, a linear reference marker, and a target marker. The frame includes a first portion fixable to a first anatomical reference point. The linear reference marker is rotatable about the first anatomical reference point to align a second anatomical reference point with the first anatomical reference point. The target marker is rotatable about the first anatomical reference point to establish an angle from the linear reference marker such that the target marker is located in a desired plane.

Most surgical neurological procedures require accurate placement of medical instruments within the patient's brain. A common neurological surgical procedure is a ventriculostomy in which a cerebral ventricle drain, shunt or catheter is implanted. The purpose of the drain or shunt (with or without a transducer or fiberoptic device) is to relieve high pressure cerebrospinal fluid (CSF) in a patient's cerebral ventricles resulting from congenital brain malformations, acute or chronic infections, tumors, intraventricular hemorrhage, normal pressure hydrocephalus or other intracranial space-occupying lesions, as well as to provide a reliable means to measure intracranial pressure or to deliver medication into the cerebrospinal fluid space.
Procedures for the placement of ventricular drains, shunts and catheters rely on the skill of the neurosurgeon. These procedures are often expensive and time consuming. After imaging the brain, the neurosurgeon forms a burr hole in the skull and guides a catheter through the burr hole toward landmarks on the ipsilateral or contralateral of the patient's head. The neurosurgeon must accurately conceptualize the internal topography of the brain during the procedure, and rely on this conceptualization to effectively place the catheter within the cerebral ventricle. In some procedures, the neurosurgeon checks the location of the catheter by imaging another CT scan of the brain following the operation. By verifying the position of the catheter within the brain, the neurosurgeon can effect longer shunt patency and decrease morbidity rates due to shunt malpositioning, as well as assure the accurate delivery of medication within the ventricle and the accurate measurement of intracranial pressure.


A device for securing a support element to an actuating lever of a valvetrain of an internal combustion. The actuating lever having a socket dome to accept a socket end of the support element and a roller pocket, with the securing device seated on the socket dome, extending through the roller pocket and splitting into two arms that extend on opposite ends of a circumferential groove below the socket end of the support element.

Securing devices for actuating levers in valve control mechanisms for internal combustion engines are known in the art. For instance, U.S. Pat. No. 5,775,280 discloses a generally U-shaped retention clip that can be used for securing an actuating lever to a support member.
Securing devices of this type are utilized, mainly, to provide a unitary subassembly of the actuating lever and support member, for assembly into a valvetrain. By providing such a subassembly, extra components and orientation errors between the components may be avoided in a vehicle assembly environment. In addition, securing the actuating lever and support member together with a securing device aids in ease of shipping.
Features are sometimes added to actuating levers to prevent dislocation of pivot elements from actuating levers, often called anti-pop-off features. Also, additional features can be incorporated into actuating levers, or support members to improve performance. Securing devices must, therefore, accommodate for these additional devices. Particularly where the actuating lever has additional features, such as anti-pop-off features, alternative clip configurations are needed.


A multiprocessor computer system implements fault resilient booting by using appliance server management. While previous systems have utilized fault resilient booting, it has required the use of a baseboard management controller chip. The present invention avoids the need for this chip by utilizing the appliance server management architecture. The testing of the processors and the determination of the bootstrap processor is controlled by the system I/O device utilizing a timer and a latch.

The use of fault resilient booting is known in the art and for example is described in U.S. Pat. No. 5,790,850. As described therein and as shown in FIG. 1, a multiprocessor system includes a number of processors 10-13 each of which include a local advance programmable interrupt controller (APIC) 14-17. The local APIC units are connected through an APIC 19 bus. An input/output APIC unit 28 is also connected to this bus. A processor bus 20 connects the processors and the memory.
In this system, when power is initially applied to the processors one of the processors is designated the bootstrap processor. One of the processors can be designated in the hardware for this function. The other processors are classified as application processors. Each of the processors undergoes a built in self test when power is initially applied. If the processor is faulty for any reason, it stores a status flag to indicate this. If the bootstrap processor is faulty, it is necessary to designate one of the application processors to handle the bootstrap function instead. U.S. Pat. No. 5,790,850 shows one method for doing this where application processors that have been tested to be good are successively examined. If all tests are passed, that application processor is designated as the bootstrap processor and that function is removed from the original bootstrap processor.
In systems of this type, the fault resilient booting is implemented in servers using the basic input output system (BIOS), the baseboard management controller (BMC) and other hardware to follow this procedure when the bootstrap processor fails. Most of this function is implemented in the baseboard management controller chip. However, the inclusion of this chip adds to the cost of the system. While this is not a problem for more expensive systems, in low cost servers, it is desirable to reduce the cost of the system.

Fault resilient booting for multiprocessor system using appliance server management


A traveling transmission apparatus for a work vehicle is disclosed. The apparatus includes a stepless change-speed unit receiving power from an engine, a gear transmission mechanism receiving power from the stepless change-speed unit and disposed rearwardly of the engine, a rear-wheel differential mechanism receiving power from the gear transmission mechanism and disposed rearwardly of the engine, and a transmission case accommodating the gear transmission mechanism and the rear-wheel differential mechanism and coupled to the rear of the engine. The stepless change-speed unit is disposed rearwardly of the gear transmission mechanism and rearwardly also of an output shaft of the rear-wheel differential mechanism.

1. Field of the Invention
The present invention relates to a traveling transmission apparatus for a work vehicle, including a stepless change-speed unit receiving power from an engine, a gear transmission mechanism receiving power from the stepless change-speed unit, and a rear-wheel differential mechanism for transmitting power from the gear transmission mechanism to rear wheels, the change-speed unit, the gear transmission mechanism and the differential mechanism all being disposed rearwardly of the engine.
2. Description of the Related Art
The traveling transmission apparatus of the above-noted type is known form e.g. the Japanese Patent Application "Kokai", No.: Hei. 11-91379 (see paragraphs [0054]-[0056] and FIGS. 1–3). In this traveling transmission apparatus, a change-speed case of the stepless change-speed unit is coupled via a main clutch housing to a flywheel housing portion disposed rearwardly of the engine and to the rear of this change-speed case, there is connected a traveling transmission case housing therein the gear transmission mechanism and the rear-wheel differential mechanism.
When the above-described conventional traveling transmission apparatus is mounted on a work vehicle, for effecting e.g. a maintenance operation of a hydraulic circuit of the stepless change-speed unit, this operation was difficult because of the poor accessibility to the stepless change-speed unit from the outside of the vehicle body. Further, regarding a desire to dispose the engine and the traveling transmission unit in a compact manner in the vicinity of the rear axle, the above construction cannot fully meet the desire because of a significant distance separating between the engine and the rear-wheel differential mechanism.

Traveling transmission apparatus for work vehicle


A computer-based placement and routing (P&R) tool stores a set of circuit patterns, each describing a separate device group by referencing each device of the device group and by indicating which device elements forming the referenced devices are interconnected by nets, a set of placement patterns, each providing a guide for placing IC device elements forming a device group described by a corresponding one of the circuit patterns and a set of routing styles to act as guides for routing nets between device elements placed in particular patterns. To produce a layout for an analog IC described by a netlist, the P&R tool identifies each set of devices in the IC forming a device group described by any of the circuit patterns. The P&R tool then generates a separate device group layout for each identified device group using the placement patterns as guides for placing device elements within the device group layout and using the routing styles as guides for routing nets interconnecting device elements within the device group layout. The P&R tool also generates a layout for each device not included in any identified device group. The tool then generates a layout for the IC incorporating each generated device and device group layout.

1. Field of the Invention
The invention relates in general to systems for generating layouts for integrated circuits (ICs) and in particular to an automated layout system for analog ICs.
2. Description of Related Art
A circuit designer typically creates an IC design in the form of a netlist referencing circuit devices to be included in the IC and indicating which conductive net is to be connected to each device terminal. A digital IC designer usually processes a netlist description of an IC using a placement and routing (P&R) tool that automatically generates an IC layout indicating the position and orientation of each device within the IC and indicating how conductors forming nets interconnecting device terminals are to be routed within the IC. When generating a layout for a digital IC, the P&R tool treats each device as a separate cell having a predetermined internal layout. The tool iteratively repositions cells and reroutes nets until it arrives at a layout solution satisfying constraints on the size and aspect ratio of the available layout area, on signal path delays, on net widths and spacing, and on power density and other constraints.
Although automated placement and routing tools are widely used for generating digital IC layouts, they are not often used to generate analog IC layouts. A typical analog IC includes circuits formed by transistors and passive devices that must be laid out in particular patterns in order for the circuits to behave properly. For example a pair of transistors forming a differential pair circuit must be closely matched and the differential pair circuit they form must have a symmetric layout in order to properly balance the differential currents they convey. To create a layout for a differential pair circuit, it is not sufficient to merely select a separate layout for each transistor, place each transistor near one another and then route nets interconnecting them. It is necessary to generate a detailed layout for the differential pair circuit as a whole, wherein the gate, drain and source components of the two transistors are appropriately matched and symmetrically distributed and interconnected. Since placement and routing algorithms developed for digital circuits are not adapted for satisfying matching and symmetry constraints and other constraints on analog circuit layouts, designers often resort to manually producing layouts for analog ICs, or for the analog portions of mixed-signal ICs, even though handcrafted layouts can be time-consuming and error-prone.
In the past decade, academia and industry have proposed both "template-driven" and "constraint driven" automated placement and routing tools for analog circuits, but the drawbacks to these systems have prevented them from being widely used. A template-driven automated layout system generates an IC layout by processing a netlist to determine whether any portion of an analog circuit it describes can fit into any one of a set of pre-designed handcrafted layout templates. Each template specifies a complete layout for a separate analog circuit such as for example a current mirror or a differential pair. Although this approach is usually fast and easy and can produce a compact layout when suitable templates are available, it lacks flexibility because it does not allow a layout designer to easily vary the layout from design-to-design when differences in layout constraints require small variations in circuit layout. For example although two current mirror circuits may be schematically similar, they cannot be laid out according to the same layout template if the current mirror circuits require transistors of differing in-factor (i.e. having differing numbers of gate fingers). Even though a designer may have previously generated a template for a current mirror using in-factor 1 transistors, the designer must manually generate another template for a schematically similar current mirror using in-factor 2 transistors. Also though two circuits are schematically similar and are formed of transistors having the same in-factor, they cannot use the same layout pattern if they are subject to differing technology constraints. Differences in technology constraints can also influence device group a layout pattern. The nets that interconnect elements of the various devices of a circuit are subject to width and spacing constraints that can vary from one IC to another depending on the fabrication technology used to make the IC. Thus the number of templates needed to enable a template-based P&R tool to layout an analog ICs having a wide variety of circuits and subject to a wide variety of constraint without much human intervention would be prohibitively large.
A constraint-driven automated layout tool generates an IC layout satisfying various constraints on the layout, including device matching and symmetry constraints, without using predetermined layout templates. FIG. 1 shows the general flow of a typical prior art constraint-driven layout tool. The tool initially analyzes input data 10 including a netlist, a circuit performance specification and technology file to identify groups of devices that are subject to device and net matching and symmetry constraints (step 12). The tool creates a database 14 indicating the constraints on each device or device group and then generates a layout for each device or device group that satisfies all device matching and symmetry constraints (step 16) in database 14. The tool then places the device and device group layouts generated at step 16 in the IC layout and routes the nets interconnecting the device terminals (step 18) to produce a final layout 20. Although the constraint-driven approach is more flexible than the template-driven layout approach, the resulting layout 20 is often not as good in many respects as handcrafted and template-driven layouts.
What is needed is a flexible automated placement and routing system for an analog or mixed signal circuit that can generate high-quality layouts.

Analog and mixed signal IC layout system


Disclosed herein are heaters for dispensing volatile air treatment chemicals. Semi-circular electrical contacts are provided in a ring-type heater, and alignment and anchoring features are provided to facilitate use of a spring to accommodate thermal expansion.

The present invention relates to heaters used to dispense air treatment chemicals, such as insect control agents, fragrances and deodorizers. More particularly, it relates to contact assemblies for carrying electricity to a heating element used therewith, and for then spreading the heat generated by the heating element around a dispensing wick.
A known type of air treatment chemical dispenser is that disclosed in U.S. Pat. No. 6,968,124, the disclosure of which is incorporated by reference. In this type of dispenser a liquid air treatment chemical is stored in a bottle. A wick dips into the liquid, and then extends upward out of the bottle. An upward end of the wick is surrounded by a ring-type electrical heater. Heating of the upward end of the wick causes air treatment chemical to be volatized from the wick, and thus the bottle, to the surrounding area.
One particularly desirable form of ring-type heater is one with a positive temperature coefficient "PTC" heating element. A PTC heating element is typically in the form of a pill-shaped tablet formed from pressed conductive granular material. Its resistivity to electrical charge generates heat, but that resistivity increases with an increase in temperature, thereby providing an inherent desirable control function against overheating.
A particularly desirable form of heater that uses a PTC heating element is the "All-Out" heater sold in India by Karamchand Appliances Pvt. Ltd. This product has a housing that is generally doughnut shaped, but hollow. A first ring-shaped electrical contact is positioned in the housing to extend around a central axial through bore, the bore being sized to receive the wick. One end of the contact connects to a prong of an external plug. At the other end there is a portion designed to abut a PTC type pill heating element.
On the other side of the PTC pill of the All-Out heater is placed a second ring-shaped electrical contact that also extends around the through bore. It has a connection to another external plug at one end. At the other end of the ring there is a portion designed to rest against an opposed side of the PTC pill. A top housing part is riveted to the lower housing part.
Electrical charge passes through the contacts of the All-Out heater to the pill, causing the pill to generate heat. The generated heat is then carried back along the contact to spread the heat around the through bore, and then to the wick. Heating of the wick facilitates volatilization of air treatment chemicals drawn up by the wick.
While this type of heater has many advantages, there are still a number of features in need of improvement. For example, because the two ring contacts are over each other in close proximity all the way around the ring, there is a theoretical potential for charge to be directed inefficiently if the parts are not precisely assembled. Further, the way some of the parts are installed inside the housing in the All-Out design is awkward, particularly with respect to insuring that small parts are properly aligned for optimal function. Also, the need to rivet the housing together adds cost and complexity.
Hence, a need exists for an improved heater for use with such volatile dispensers.

Heater contact assembly for volatile liquid dispenser


According to the present invention, there is provided a fuel tank comprising a separator wall which separates an interior of the fuel tank into an air chamber and a fuel chamber. The separator wall is deformed according to an amount of fuel in the fuel chamber while the separator wall is in contact with a surface of the fuel in the fuel chamber. Further, the tank comprises fuel flow restricting elements extending within the fuel chamber to suppress movement of the fuel in fuel tank.

1. Field of the Invention
The invention relates to a fuel tank comprising a separator film.
2. Description of the Related Art
In order to prevent fuel vapor produced in a fuel tank from being discharged to the atmosphere, a charcoal canister containing activated carbon is connected to an engine. The vapor in a space above the surface of the fuel stored in the tank is introduced into the canister and is adsorbed on the activated carbon thereof. A large amount of the vapor, introduced into the canister, needs a large canister. Therefore, it is preferable to minimize the amount of the vapor produced in the tank in order to reduce the size of the canister.
In order to minimize the amount of vapor produced in the tank, a fuel tank which comprises a fuel-impermeable separator film in an interior of the tank, as disclosed in Japanese Unexamined Utility Model Publication No. 60-158923, has been developed. The film is in contact with the surface of the fuel in the tank to reduce the space above the fuel surface and moves up and down with the movement of the fuel surface. The small space above the fuel surface leads to a small amount of vapor being produced in the tank.
In the tank described above, if the fuel moves or oscillates in the fuel chamber, the separator film moves. As a result, the separator film may be broken.
Therefore, the object of the invention is to provide a tank, comprising a separator film, which is designed to prevent the separator film from being broken.


The present invention relates to novel amidino compounds of formula (I),

The present invention relates to novel amidino compounds, to a process for their manufacture, to pharmaceutical compositions containing them, and to their use in therapy, in particular their use as selective inhibitors of inducible nitric oxide synthase.
Nitric oxide is the endogenous stimulator of the soluble guanylate cyclase enzyme and is involved in a number of biological actions. Excess nitric oxide production is also thought to be involved in a number of conditions, including septic shock and many inflammatory diseases. The biochemical synthesis of nitric oxide from L-arginine is catalysed by the enzyme NO synthase. Many inhibitors of NO synthase have been described and proposed for therapeutic use.
More recently, it has been an object in this field to provide NO synthase inhibitors displaying selectivity for inducible NO synthase (iNOS) over endothelial NO synthase (eNOS) and/or neuronal NO synthase (nNOS).
Thus WO93/13055 describes selective NO synthase inhibitors of formula
and salts, and pharmaceutically acceptable esters and amides thereof, in which:
R1 is a C1-6 straight or branched chain alkyl group, a C2-6alkenyl group, a C2-6alkynyl group, a C3-6cycloalkyl group or a C3-6cycloalkylC1-6alkyl group;
Q is an alkylene, alkenylene or alkynylene group having 3 to 6 carbon atoms and which may optionally be substituted by one or more C1-3alkyl groups;
a group of formula xe2x80x94(CH2)pX(CH2)qxe2x80x94 where p is 2 or 3, q is 1 or 2 and X is S(O)x where x is 0, 1 or 2, O or NR2 where R2 is H or C1-6alkyl; or
a group of formula xe2x80x94(CH2)rA(CH2)sxe2x80x94 where r is 0, 1 or 2, s is 0, 1 or 2 and A is a 3 to 6 membered carbocylic or heterocyclic ring which may optionally be substituted by one or more suitable substituents such as C1-6alkyl, C1-6alkoxy, hydroxy, halo, nitro, cyano, trifluoroC1-6alkyl, amino C1-6alkylamino or diC1-6alkylamino.
The co-pending International application WO 98/30537 also describes certain amidino compounds which are selective inhibitors of inducible nitric oxide synthase.
We have now found a novel class of compounds which as well as being selective iNOS inhibitors, display advantages including that they have a relatively long half-life, are orally bioavailable when administered in vivo, and may be prepared from relatively cheap starting materials.
Therefore, according to the present invention there is provided a compound of formula (I)
or a salt, solvate, or physiologically functional derivative thereof;
wherein R1 is selected from C1-4 alkyl, C3-4 cycloalkyl, C1-4 hydroxyalkyl, and C1-4 haloalkyl.
In formula (I), R1 is preferably C1-4 alkyl, most preferably, methyl.
The compounds of formula (I) include two chiral centres i.e. the carbon which bears the R1 substituent and the asymmetric centre in the amino acid group. It is intended that formula (I) includes all optical isomers either in substantially pure form or admixed in any proportions. In a preferred aspect, the amino acid group is in the natural L configuration. In a further preferred aspect the carbon bearing the group R1 is in the R configuration. In the most preferred aspect, the amino acid is in the natural L configuration and the carbon bearing the group R1 is in the R configuration. Throughout this specification, where the stereochemistry of two chiral centres within a molecule are given, the first configuration refers to the amino acid xcex1 carbon and the second refers to the carbon bearing the R1 substituent, for example, stereochemistry designated (R,S) means (R)-stereochemistry at the amino acid a carbon, and (S)-stereochemistry at the carbon bearing the R1 substituent.
Thus, in a further aspect, the present invention provides a compound selected from:
S-[(R)-2-(1-iminoethylamino)propyl]-L-cysteine;
S-[(S)-2-(1-iminoethylamino)propyl]-L-cysteine;
S-[(R/S)-2-(1-iminoethylamino)propyl]-L-cysteine;
S-[(R)-2-(1-iminoethylamino)propyl]D-cysteine;
S-[(S)-2-(1-iminoethylamino)propyl]-D-cysteine;
S-[(R/S)-2-(1-iminoethylamino)propyl]-D-cysteine;
S-[(R/S)-2-(1-iminoethylamino)butyl]-L-cysteine;
S-[(R/S)-2-(1-iminoethylamino,2-cyclopropyl)ethyl]-L-cysteine; and
S-[(R/S)-2-(1-iminoethylamino,3-hydroxy)propyl]-L-cysteine.
and salts, solvates, and physiologically functional derivatives thereof.
In a preferred aspect, the present invention provides S-[(R)-2-(1-iminoethylamino)propyl]-L-cysteine or a salt, solvate, or physiologically functional derivative thereof. In a particularly preferred aspect, the present invention provides S-[(R)-2-(1-iminoethylamino)propyl]-L-cysteine or a salt thereof.
It is to be understood that the present invention covers all combinations of particular and preferred groups described herein.
Salts and solvates of compounds of formula (I) which are suitable for use in medicine are those wherein the counterion or associated solvent is pharmaceutically acceptable. However, salts and solvates having non-pharmaceutically acceptable counterions or associated solvents are within the scope of the present invention, for example, for use as intermediates in the preparation of other compounds of formula (I) and their pharmaceutically acceptable salts, solvates, and physiologically functional derivatives.
By the term xe2x80x9cphysiologically functional derivativexe2x80x9d is meant a chemical derivative of a compound of formula (I) having the same physiological function as the free compound of formula (I), for example, by being convertible in the body thereto. According to the present invention, examples of physiologically functional derivatives include esters, amides, and carbamates; preferably esters and amides.
Suitable salts according to the invention include those formed with both organic and inorganic acids or bases. Pharmaceutically acceptable acid addition salts include those formed from hydrochloric, hydrobromic, sulphuric, citric, tartaric, phosphoric, lactic, pyruvic, acetic, trifluoroacetic, succinic, oxalic, fumaric, maleic, oxaloacetic, methanesulphonic, ethanesulphorlic, p-toluenesulphonic, benzenesulphonic, and isethionic acids. Pharmaceutically acceptable base salts include ammonium salts, alkali metal salts such as those of sodium and potassium, alkaline earth metal salts such as those of calcium and magnesium and salts with organic bases such as dicyclohexyl amine and N-methyl-D-glucamine.
Pharmaceutically acceptable esters and amides of the compounds of formula (I) may have the acid group converted to a C1-6alkyl, aryl, aryl C1-6 alkyl, or amino acid ester or amide. Pharmaceutically acceptable amides and carbamates of the compounds of formula (I) may have an amino group converted to a C1-6alkyl, aryl, aryl C1-6 alkyl, or amino acid amide or carbamate.
As mentioned above, the compounds of formula (I) are inhibitors of NO synthase as demonstrated in the NOS inhibition assays below.
Therefore, compounds of formula (I) and their pharmaceutically acceptable salts, solvates, and physiologically functional derivatives have use in the prophylaxis and treatment of clinical conditions for which an inhibitor of NO synthase is indicated, in particular, an inhibitor of iNOS. Such conditions include inflammatory conditions, shock states, immune disorders, and disorders of gastrointestinal motility. The compounds of formula (I) and pharmaceutically acceptable salts,solvates, and physiologically functional derivatives thereof may also be of use in the prophylaxis and treatment of diseases of the central nervous system including migraine.
By shock states is meant those resulting from overproduction of NO, such as septic shock, haemorrhagic shock, traumatic shock, or shock caused by fulminant hepatic failure or by therapy with cytokines such as TNF, IL-1 and IL-2 or therapy with cytokine-inducing agents, for example 5,6-dimethylxanthenone acetic acid.
Examples of inflammatory conditions and immune disorders include those of the joint, particularly arthritis (e.g. rheumatoid arthritis, osteoarthritis, prosthetic joint failure), or the gastrointestinal tract (e.g. ulcerative colitis, Crohn""s disease, and other inflammatory bowel diseases, gastritis and mucosal inflammation resulting from infection, the enteropathy provoked by non-steroidal antiinflammatory drugs), of the lung (e.g. adult respiratory distress syndrome, asthma, cystic fibrosis, or chronic obstructive pulmonary disease), of the heart (e.g. myocarditis), of nervous tissue (e.g. multiple sclerosis), of the pancreas (e.g. diabetes melitus and complications thereof), of the kidney (e.g. glomerulonephritis), of the skin (e.g. dermatitis, psoriasis, eczema, urticaria), of the eye (e.g. glaucoma) as well as of transplanted organs (e.g. rejection) and multi-organ diseases (e.g. systemic lupus erythematosis) and inflammatory sequelae of viral or bacterial infections. There is also evidence that iNOS inhibitors may be useful in the prophylaxis or treatment of bacterial infections (e.g. pneumonia), in particular, by reducing bacterial load in an infected mammal.
Furthermore, there is evidence for overproduction of NO by iNOS in atherosclerosis and following hypoxic or ischaemic insults (with or without reperfusion), for example in the brain or in ischaemic heart disease.
Disorders of gastrointestinal motility include ileus, for example post-operative ileus and ileus during sepsis.
By diseases of the central nervous system is meant those for which overproduction of NO is implicated, for example migraine, psychosis, anxiety, schizophrenia, sleep disorders, cerebral ischaemia, CNS trauma, epilepsy, multiple sclerosis, AIDS dementia, chronic neurodegenerative disease (e.g. Lewy Body Dementia, Huntington""s disease, Parkinson""s disease, or Alzheimer""s disease) and acute and chronic pain, and conditions in which non-adrenergic non-cholinergic nerve may be implicated such as priapism, obesity and hyperphagia.
Examples of acute pain include musculoskeletal pain, post operative pain and surgical pain. Examples of chronic pain include chronic inflammatory pain (e.g. rheumatoid arthritis and osteoarthritis), neuropathic pain (e.g. post herpetic neuralgia, diabetic neuropathies associated with diabeties, trigeminal neuralgia, pain associated with functional bowel disorders, e.g. irritable bowel syndrome, non cardiac chest pain and sympathetically maintained pain) and pain associated with cancer and fibromyalgia.
Furthermore, inhibition of NO synthase may be of advantage in preventing the lymphocyte loss associated with HIV infection, in increasing the radiosensitivity of tumours during radiotherapy and in reducing tumour growth, tumour progression, angiogenesis, and metastasis.
Accordingly, the present invention provides a method for the prophylaxis or treatment of a clinical condition in a mammal, such as a human, for which an inhibitor of nitric oxide synthase, for example, an iNOS inhibitor is indicated, which comprises administration of a therapeutically effective amount of a compound of formula (I), or a pharmaceutically acceptable salt, solvate, or physiologically functional derivative thereof. In particular, the present invention provides a method for the prophylaxis or treatment of an inflammatory and/or immune disorder, such as arthritis or asthma. In a preferred aspect the present invention provides a method for the prophylaxis or treatment of a clinical condition selected from arthritis, asthma, ileus, and migraine. In a further aspect, the present invention provides a method for the prophylaxis or treatment of a bacterial infection.
In the alternative, there is also provided a compound of formula (I) or a pharmaceutically acceptable salt, solvate, or physiologically functional derivative thereof for use in medical therapy, particularly, for use in the prophylaxis or treatment of a clinical condition in a mammal, such as a human, for which an inhibitor of nitric oxide synthase, for example an iNOS inhibitor, is indicated. In particular, there is provided a compound of formula (I) or a pharmaceutically acceptable salt, solvate, or physiologically functional derivative thereof for the prophylaxis or treatment of an inflammatory and/or immune disorder, such as arthritis or asthma. In a preferred aspect, there is provided a compound of formula (I) or a pharmaceutically acceptable salt, solvate, or physiologically functional derivative thereof for the prophylaxis or treatment of arthritis, asthma, ileus, and migraine. In a further aspect, there is provided a compound of formula (I) or a pharmaceutically acceptable salt, solvate, or physiologically functional derivative thereof for the prophylaxis or treatment of a bacterial infection.
The amount of a compound of formula (I), or a pharmaceutically acceptable salt, solvate, or physiologically functional derivative thereof which is required to achieve a therapeutic effect will, of course, vary with the particular compound, the route of administration, the subject under treatment, and the particular disorder or disease being treated. The compounds of the invention may be administered orally or via injection at a dose of from 0.1 to 1500 mg/kg per day, preferably 0.1 to 500 mg/kg per day. The dose range for adult humans is generally from 5 mg to 35 g/day and preferably 5 mg to 2 g/day. Tablets or other forms of presentation provided in discrete units may conveniently contain an amount of compound of the invention which is effective at such dosage or as a multiple of the same, for instance, units containing 5 mg to 500 mg, usually around 10 mg to 200 mg.
While it is possible for the compound of formula (I), or a pharmaceutically acceptable salt, solvate, or physiologically functional derivative thereof to be administered alone, it is preferable to present it as a pharmaceutical formulation.
Accordingly, the present invention further provides a pharmaceutical formulation comprising a compound of formula (I) or a pharmaceutically acceptable salt, solvate, or physiologically functional derivative thereof, and a pharmaceutically acceptable carrier or excipient, and optionally one or more other therapeutic ingredients.
The present invention also provides the use of a compound of formula (I), or a pharmaceutically acceptable salt, solvate, or physiologically functional derivative thereof in the manufacture of a medicament for the prophylaxis or treatment of a clinical condition for which an inhibitor of nitric oxide synthase, for example an iNOS inhibitor, is indicated, for example an inflammatory and/or immune disorder, such as arthritis or asthma. In a preferred aspect, there is provided a compound of formula (I), or a pharmaceutically acceptable salt, solvate, or physiologically functional derivative thereof in the manufacture of a medicament for the prophylaxis or treatment of a clinical condition selected from arthritis, asthma, ileus, and migraine. In a further aspect, there is provided a compound of formula (I), or a pharmaceutically acceptable salt, solvate, or physiologically functional derivative thereof in the manufacture of a medicament for the prophylaxis or treatment of a bacterial infection.
Hereinafter, the term xe2x80x9cactive ingredientxe2x80x9d means a compound of formula (I), or a pharmaceutically acceptable salt, solvate, or physiologically functional derivative thereof.
The formulations include those suitable for oral, parenteral (including subcutaneous, intradermal, intramuscular, intravenous and intraarticular), inhalation (including fine particle dusts or mists which may be generated by means of various types of metered dose pressurised aerosols, nebulisers or insufflators), rectal and topical (including dermal, buccal, sublingual and intraocular) administration although the most suitable route may depend upon for example the condition and disorder of the recipient. The formulations may conveniently be presented in unit dosage form and may be prepared by any of the methods well known in the art of pharmacy. All methods include the step of bringing the active ingredient into association with the carrier which constitutes one or more accessory ingredients. In general the formulations are prepared by uniformly and intimately bringing into association the active ingredient with liquid carriers or finely divided solid carriers or both and then, if necessary, shaping the product into the desired formulation.
Formulations of the present invention suitable for oral administration may be presented as discrete units such as capsules, cachets or tablets each containing a predetermined amount of the active ingredient; as a powder or granules; as a solution or a suspension in an aqueous liquid or a non-aqueous liquid; or as an oil-in-water liquid emulsion or a water-in-oil liquid emulsion. The active ingredient may also be presented as a bolus, electuary or paste.
A tablet may be made by compression or moulding, optionally with one or more accessory ingredients. Compressed tablets may be prepared by compressing in a suitable machine the active ingredient in a free-flowing form such as a powder or granules, optionally mixed with a binder, lubricant, inert diluent, lubricating, surface active or dispersing agent. Moulded tablets may be made by moulding in a suitable machine a mixture of the powdered compound moistened with an inert liquid diluent. The tablets may optionally be coated or scored and may be formulated so as to provide slow or controlled release of the active ingredient therein.
Formulations for parenteral administration include aqueous and non-aqueous sterile injection solutions which may contain anti-oxidants, buffers, bacteriostats and solutes which render the formulation isotonic with the blood of the intended recipient; and aqueous and non-aqueous sterile suspensions which may include suspending agents and thickening agents. The formulations may be presented in unit-dose or multi-dose containers, for example sealed ampoules and vials. and may be stored in a freeze-dried (lyophilised) condition requiring only the addition of the sterile liquid carrier, for example saline or water-for-injection, immediately prior to use. Extemporaneous injection solutions and suspensions may be prepared from sterile powders, granules and tablets of the kind previously described.
Formulations for rectal administration may be presented as a suppository with the usual carriers such as cocoa butter or polyethylene glycol.
Formulations for topical administration in the mouth, for example buccally or sublingually, include lozenges comprising the active ingredient in a flavoured basis such as sucrose and acacia or tragacanth, and pastilles comprising the active ingredient in a basis such as gelatin and glycerin or sucrose and acacia.
Preferred unit dosage formulations are those containing an effective dose, as hereinbefore recited, or an appropriate fraction thereof, of the active ingredient.
It should be understood that in addition to the ingredients particularly mentioned above, the formulations of this invention may include other agents conventional in the art having regard to the type of formulation in question, for example those suitable for oral administration may include flavouring agents.
According to a further aspect of the invention, there is provided a process for preparing a compound of formula (I) or a salt, solvate, or physiologically functional derivative thereof which comprises:
(i) reaction of the compound of formula (II)
or an optical isomer, a salt, or a protected derivative thereof, wherein R1 is as defined above, with a compound of formula (III)
or a salt thereof, wherein L is a leaving group, most suitably a C1-6 alkoxy group, for example ethoxy, or an alkylthio, aralkylthio or arylthio group e.g. a benzylthio, or 1- or 2-naphthylmethylthio group; followed by the following steps in any order:
(ii) optional removal of any protecting groups;
(iii) optional separation of an optical isomer from a mixture of optical isomers;
(iv) optional conversion of the product to a corresponding salt, solvate, or physiologically functional derivative thereof.
When L is C1-6 alkoxy, the reaction in step (i) above may be effected in solution at alkaline pH, for example pH 8 to 11, suitably at pH 10.5, and at a low temperature, for example xe2x88x925xc2x0 C. to 20xc2x0 C., suitably 0 to 5xc2x0 C. When L is an alkylthio, aralkylthio, or arylthio group, the reaction may be effected in an organic solvent e.g. tetrahydrofuran or a C1-4alcohol such as ethanol, at a moderate temperature e.g. 10 to 40xc2x0 C., suitably at ambient temperature.
Compounds of formula (III) and salts thereof are available commercially or may be prepared by methods of organic chemistry well known to the person skilled in the art, for example, as described by Shearer et al in Tetrahedron Letters, 1997, 38, 179-182.
Compounds of formula (II) and salts and protected derivatives thereof may be prepared from a compound of formula (IV):
or a protected derivative thereof, by coupling with a compound of formula (V)
or a protected derivative thereof, wherein R1 is as defined above and L1 is a leaving group, for example halo, such as bromo, or an alkyl, aryl or aralkyl sulphonate ester, such as toluenesulphonyl.
Protected derivatives of a compound of formula (IV) e.g. N-t-butoxycarbonyl cysteine t-butyl ester may react with compounds of formula (V) under conditions in an appropriate organic solvent (e.g. toluene) in a reaction mediated by a base such as 1,8-diazabicyclo[5.4.0]undec-7-ene or a similar agent which would be recognised by one skilled in the art.
Alternatively, compounds of formula (II) and salts and protected derivatives thereof may be prepared by reduction (for example, using a metal hydride complex) of a compound of formula (VI)
or a protected derivative thereof, wherein R1 is as defined above.
Compounds of formula (VI) may be prepared by methods analogous to those described by Yanagisawa et al in J. Med. Chem 30 (11), 1984-91, (1987) and Hassner and Dehaen in J. Org. Chem., 55, 5505-5510, (1990). Thus, reaction of the compound of the formula (IV) or a protected derivative thereof (for example, where the amino group is protected with an acyl group such as t-butoxycarbonyl and the carboxylic acid group is protected as an ester, such as a tert-butyl ester) with nitromethane and the appropriate aldehyde R1CHO, wherein R1 is as defined above, in the presence of piperidine yields a nitro compound of formula (VI) or a protected derivative thereof.
Compounds of formula (II) or a protected derivative thereof may also be prepared by reaction of a compound of formula (VII)
or a protected derivative thereof wherein R1 is as defined above, with an aziridine of formula (VIII).
or a protected derivative thereof, for example, wherein the amine is protected with an acyl group such as t-butoxycarbonyl and the acid is protected as an ester such as C1-4alkyl ester. The reaction of the compounds of formulae (VII) and (VIII) may be effected in an inert solvent, such as chloroform in the presence of a Lewis acid, such as BF3(OEt)2.
The compounds of formulae (IV), (V), (VII), and (VIII) and protected derivatives thereof are commercially available or may be prepared by methods of organic chemistry well known to the person skilled in the art.
The protecting groups used in the preparation of compounds of formula (I) may be used in a conventional manner, for example, using methods described in xe2x80x9cProtective Groups in Organic Synthesisxe2x80x9d by Theodora W Green, 2nd edition (John Wiley and Sons, 1991) which also describes methods for the removal of such groups.
In the above reactions, primary amines are suitably protected using acyl groups, such as t-butoxycarbonyl or benzyloxycarbonyl groups which may be removed under acidic conditions, for example, by treatment with hydrochloric acid or hydrobromic acid, or by hydrogenolysis.
As will be appreciated by the person skilled in the art use of such protecting groups may include orthogonal protection of amino groups in the compounds of formula (II) to facilitate the selective removal of one group in the presence of another, thus enabling selective functionalisation of a single amino function. For example, a benzyloxycarbonyl group may be selectively removed by hydrogenolysis. A person skilled in the art will also appreciate other orthogonal protection strategies, available by conventional means as described in Theodora W Green (vide supra).
The enantiomeric compounds of the invention may be obtained (a) by separation of the components of the corresponding racemic mixture, for example, by means of a chiral chromatography column, enzymatic resolution methods or preparing and separating suitable diastereoisomers, or (b) by direct synthesis from the appropriate chiral intermediates by the methods described above.
Optional conversion of a compound of formula (I) to a corresponding salt may conveniently be effected by reaction with the appropriate acid or base. Optional conversion of a compound of formula (I) to a corresponding solvate or physiologically functional derivative may be effected by methods known to those skilled in the art.
According to a further aspect, the present invention provides novel intermediates for the preparation of compounds of formula (I), for example: compounds of formula (II) as defined above, or an optical isomer, a salt, or a protected derivative thereof; particularly, a compound selected from:
(R,R)-t-butyl-2N-t-butoxycarbonyl-2,6-diamino-5-methyl-4-thiohexanoate;
(R,S)-t-butyl-2N-t-butoxycarbonyl-2,6-diamino-5-methyl-4-thiohexanoate;
(S,S)-t-butyl-2N-t-butoxycarbonyl-2,6-diamino-5-methyl-4-thiohexanoate;
(S,R)-t-butyl-2N-t-butoxycarbonyl-2,6-diamino-5-methyl-4-thiohexanoate;
(R,R/S)-t-butyl-2N-t-butoxycarbonl-2,6-diamino-5-ethyl-4-thiohexanoate;
(R,R/S)-t-butyl-2N-t-butoxycarbonyl-2,6-diamino-5-butoxymethyl-4-thiohexanoate;
(R,R/S)-t-butyl-2N-t-butoxycarbonyl-2,6-diamino-5-cyclopropyl-4-thiohexanoate;
(R,R)-t-butyl-2N-t-butoxycarbonyl-6N-benzyloxycarbonyl-2,6-diamino-5-methyl-4-thiohexanoate;
(R,S)-t-butyl-2N-t-butoxycarbonyl-6N-benzyloxycarbonyl-2,6-diamino-5-methyl-4-thiohexanoate;
(S,S)-t-butyl-2N-t-butoxycarbonyl-6N-benzyioxycarbonyl-2,6-diamino-5-methyl-4-thiohexanoate;
(S,R)-t-butyl-2N-t-butoxycarbonyl-6N-benzyloxycarbonyl-2,6-diamino-5-methyl-4-thiohexanoate;
(R,R/S)-t-butyl-2N-t-butoxycarbony-6N-benzyloxycarbonyl-2,6-diamino-5-ethyl-4-thiohexanoate; and
(R,R/S)-t-butyl-2N-t-butoxycarbony-6N-benzytoxycarbonyl-2,6-diamino-5-butoxymethyl-4-thiohexanoate.
In a particular aspect of the invention, the compound of formula (II) is selected from (R,R)-t-butyl-2N-t-butoxycarbonyl-2,6-diamino-5-methyl-4-thiohexanoate and (R,R)-t-butyl-2N-t-butoxycarbonyl-6N-benzyloxycarbonyl-2,6-diamino-5-methyl-4-thiohexanoate.
Certain protected derivatives of the compounds of formula (VI) are also useful as intermediates for the preparation of compounds of formula (II); particularly (R,R/S)-t-butyl-2N-t-butoxycarbonyl-2-amino-5-cyclopropyl-6-nitro-4-thiohexanoate.
Certain protected derivatives of the compounds of formula (I) are also useful as intermediates for the preparation of compounds of formula (I); particularly a compound selected from:
(R,R)-t-butyl-2N-t-butoxycarbonyl-6N-(1-iminoethyl)-2,6-diamino-5-methyl-4-thiohexanoate;
(R,S)-t-butyl-2N-t-butoxycarbonyl-6N-(1-iminoethyl)-2,6-diamino-5-methyl-4-thiohexanoate;
(S,S)-t-butyl-2N-t-butoxycarbonyl-6N-(1-iminoethyl)-2,6-diamino-5-methyl-4-thiohexanoate;
(S,R)-t-butyl-2N-t-butoxycarbonyl-6N-(1-iminoethyl)-2,6-diamino-5-methyl-4-thiohexanoate;
(R,R/S)-t-butyl-2N-t-butoxycarbonyl-6N-(1-iminoethyl)-2,6-diamino-5-ethyl-4-thiohexanoate;
(R,R/S)-t-butyl-2N-t-butoxycarbonyl-6N-(1-iminoethyl)-2,6-diamino-5-butoxymethyl-4-thiohexanoate; and
(R,R/S)-t-butyl-2N-t-butoxycarbonyl-6N-(1-iminoethyl)-2,6-diamino-5-cyclopropyl-4-thiohexanoate;
and salts and solvates thereof.
In a particular aspect of the invention, the protected derivative of formula (I) is (R,R)-t-butyl-2N-t-butoxycarbonyl-6N-(1-iminoethyl)-2,6-diamino-5-methyl-4-thiohexanoate or a salt or solvate thereof.

Abstract: wherein R1 is selected from C1-4 alkyl, C3-4 cycloalkyl, C1-4 hydroxyalkyl, and C1-4 haloalkyl; to a process for their manufacture, to pharmaceutical compositions containing them, and to their use in therapy, in particular their use as selective inhibitors of inducible nitric oxide synthase.


The invention is a renewable adsorbent material, amine-functionalized chitin (AFC) that can remove the following munitions compounds from solution while providing a concentration-dependent color change: NTO, DNAN, and TNT. Adsorption of the munitions constituents can be adjusted by pH; neutral pH provides maximum adsorption. NTO can desorb from the AFC at pH levels of 2 and 12; DNAN and TNT remain attached to AFC once adsorbed.

The contamination of soil water from testing and disposal of munitions is a global concern. Common munitions (explosive) compounds such as Nitrotriazolone (NTO), 2,4-dinitroanisole (DNAN), and trinitrotoluene (TNT) can contaminate soil and groundwater are toxic, both acute and chronically. Munitions compounds are resistant to natural microbiological degradation. Even low levels can cause severe effects to an eco-system.
The Department of Defense (DoD) has estimated that, in the U.S. alone, munitions contaminated 15 million acres of land with clean-up costs ranging from $3-$35 billion.
Naturally occurring chitins have been successfully used to remove metal contaminants from water. However, the primary ingredient in common munitions compounds is nitrogen rather than metal. There are no naturally occurring chitins which bind to nitrogen and extract munitions contaminants at a high enough rate for effective remediation.
There is an unmet need for substances which can be produced in abundant supply to remove munitions compounds from underground water supplies, lakes, rivers and tributaries and oceans on global scale.

In situ testing apparatus for detecting and removing munitions compounds from water

UNITED STATES OF AMERICA AS REPRESENTED BY THE SECRETARY OF THE ARMY


The oscillator includes: a first oscillator circuit in which first and second transistors cross-connected to each other are connected to a resonant circuit; and a second oscillator circuit in which third and fourth transistors cross-connected to each other are connected to a resonant circuit, wherein a coupling capacitor and coupling resistor are serially provided between a collector terminal of the first transistor and a base terminal of the fourth transistor, and a coupling capacitor and coupling resistor are serially provided between a collector terminal of the second transistor and a base terminal of the third transistor, and a coupling capacitor and coupling resistor are serially provided between a collector terminal of the third transistor and a base terminal of the first transistor, and a coupling capacitor and coupling resistor are serially provided between a collector terminal of the fourth transistor and a base terminal of the second transistor. On this account, it is possible to suppress noises and reduce power consumption.

A communication device, such as a mobile phone, includes a voltage controlled oscillator as a local oscillator. The voltage controlled oscillator is required to have the accuracy of signal Generation (for example, quadrature signals which are 90° out of phase with each other), and in addition to this, a simpler circuit and lower power consumption for realizing a mobile system.
FIGS. 9 to 15 show conventional structures of an oscillator for generating a quadrature signal.
An oscillator (hereinafter referred to as a first conventional technique) shown in FIGS. 9(a) and 9(b) uses a voltage controlled oscillator (VCO), running at twice the frequency of the desired quadrature signals, and a divide-by-two circuit shown in FIG. 9(a). The divide-by-two circuit is usually a digital master-slave flip flop circuit. In the digital master-slave flip flop circuit, outputs Q and QB of a mater flip flop are connected with inputs D and DB of a slave flip flop, respectively, and outputs Q and QB of the slave flip flop are fed back to inputs DB and B of the master flip flop, respectively. Note that an oscillating signal (a signal having twice the frequency of the desired signal, see FIG. 9(b)) from the VCO is used as a CLK signal. Therefore, the outputs (Q and QB) of each flip flop are 180° out of phase, and the output Q (QB) of the master flip flop and the output Q (QB) of the slave flip flop are 90° out of phase (see FIG. 9(b)). That is, the output Q (QB) of the master flip flop can be used for an f signal, and the output Q (QB) of the slave flip flop can be used for a Q signal.
Moreover, oscillators (hereinafter referred to as a second conventional technique) disclosed in Patent Document 1 (U.S. Pat. No. 6,404,293 B1) and Non-Patent Document 1 (A. Rofougaran et al., "A 900 MHz CMOS LC oscillator with quadrature outputs," Int. Solid-State Circuits Conference, San Francisco, Calif, 1996, pp. 316–317.) are arranged as follows.
As shown in FIG. 10, each of paired oscillator circuits A and B includes two coils, two capacitors, two N-channel MOS transistors cross-connected with each other, and a constant current source.
For example, in the oscillator circuit A, a coil 826 and a capacitor 827 are connected in parallel with each other between a high potential end power source and a drain terminal of an N-channel MOS transistor 818. Moreover, a coil 828 and a capacitor 829 are connected in parallel with each other between the high potential end power source and a drain terminal of an N-channel MOS transistor 820. Further, a gate terminal of the MOS transistor 818 is connected with the drain terminal of the MOS transistor 820, and a gate terminal of the MOS transistor 820 is connected with the drain terminal of the MOS transistor 818. Further, a source terminal of the MOS transistor 818 and a source terminal of the MOS transistor 820 are connected with a constant current source 810.
The oscillator circuits A and B are connected with each other via four MOS transistors (834, 836, 838 and 840). For example, a drain terminal of the N-channel MOS transistor 834 is connected with the drain terminal of the MOS transistor 818 of the oscillator circuit A, a gate terminal of the N-channel MOS transistor 834 is connected with a drain terminal of a MOS transistor 824 of the oscillator circuit B, and a source terminal of the N-channel MOS transistor 834 is connected with the constant current source. Moreover, a drain terminal of the N-channel MOS transistor 838 is connected with a drain terminal of a MOS transistor 822 of the oscillator circuit B, a gate terminal of the N-channel MOS transistor 838 is connected with the drain terminal of the MOS transistor 818 of the oscillator circuit A, and a source terminal of the N-channel MOS transistor 838 is connected with the constant current source.
Moreover, an oscillator (hereinafter referred to as a third conventional technique) disclosed in Patent Document 2 (U.S. Pat. No. 5,912,596) is arranged as follows.
As shown in FIG. 11, each of paired oscillator circuits A and B includes one P-channel MOS transistor, two coils, one variable capacitor, four N-channel MOS transistors and a constant current source.
For example, in the oscillator circuit A, a coil 52 is connected between a drain terminal of a P-channel MOS transistor 82 and an N-channel MOS transistor 76, and a coil 50 is connected between the drain terminal of the MOS transistor 82 and an N-channel MOS transistor 74. A source terminal of the MOS transistor 82 is connected with a Vdd, and a gate terminal of the MOS transistor 82 is connected with a bias. Moreover, a variable capacitor 56 is provided between a drain terminal of the MOS transistor 74 and a drain terminal of the MOS transistor 76. Further, a source terminal of the MOS transistor 74, a source terminal of the MOS transistor 76, a source terminal of a MOS transistor 72 and a source terminal of a MOS transistor 78 are connected with each other, and those are connected with the current source. Further, a drain terminal of the MOS transistor 72 is connected with a gate terminal of the MOS transistor 76, and a drain terminal of the MOS transistor 78 is connected with a gate terminal of the MOS transistor 74.
The oscillator circuits A and B are connected with each other via electrodes of eight MOS transistors (60, 62, 64, 66, 72, 74, 76 and 78) and two variable capacitors 46 and 48. For example, a gate terminal of the MOS transistor 78 of the oscillator circuit A is connected with a drain terminal of the MOS transistor 62 of the oscillator circuit B. A gate terminal of the MOS transistor 72 of the oscillator circuit A is connected with a drain terminal of the MOS transistor 64 of the oscillator circuit B. Moreover, two variable capacitors 46 and 48 are connected in parallel with each other between the drain terminal of the MOS transistor 74 and the drain terminal of the MOS transistor 64.
Moreover, an oscillator (hereinafter referred to as a fourth conventional technique) disclosed in Patent Document 3 (U.S. Pat. No. 6,639,481 B1) is arranged as follows.
As shown in FIG. 12, each of paired oscillator circuits A and B includes two P-channel MOS transistors cross-connected with each other, six variable capacitors, two N-channel MOS transistors cross-connected with each other, and a variable constant current source.
For example, in the oscillator circuit A, a source terminal of a P-channel MOS transistor 54 is connected with a source terminal of a P-channel MOS transistor 56, a gate terminal of the MOS transistor 54 is connected with a drain terminal of the MOS transistor 56, and a gate terminal of the MOS transistor 56 is connected with a drain terminal of the MOS transistor 54. Moreover, a source terminal of an N-channel MOS transistor 58 is connected with a source terminal of the N-channel MOS transistor 60, and those are connected with a constant current source 62. Further, a gate terminal of the MOS transistor 58 is connected with a drain terminal of the MOS transistor 60, and a gate terminal of the MOS transistor 60 is connected with a drain terminal of the MOS transistor 58. Moreover, the drain terminal of the MOS transistor 56 is connected with the drain terminal of the MOS transistor 60, and the drain terminal-of the MOS transistor 54 is connected with the drain terminal of the MOS transistor 58. Moreover, two variable capacitors 64 and 66 are serially connected with each other between the drain terminal of the MOS transistor 54 and the drain terminal of the MOS transistor 56. Moreover, four variable capacitors 68, 70, 72 and 74 are serially connected with each other between the drain terminal of the MOS transistor 54 and the drain terminal of the MOS transistor 56.
Two oscillator circuits A and B are connected with each other via two transformers 25 and 27. For example, the transformer 25 includes two windings, and one end of one winding is connected between the variable capacitors 68 and 70 in the oscillator circuit A, and another end of the winding is connected between the variable capacitors 72 and 74 in the oscillator circuit A. Moreover, one end of another winding is connected with a drain terminal of an N-channel MOS transistor 18 in the oscillator circuit B, and another end of the winding is connected with a drain terminal of an N-channel MOS transistor 20.
As shown in FIGS. 13, 14(a) to 14(d) and 15, Patent Document 4 (U.S. Pat. No. 6,456,167 B1) and Non-Patent Documents 2 (J. van der Tang, et al., "Analysis and design of an optimally coupled 5-GHz quadrature LC oscillator," IEEE Journal of Solid-State Circuits, vol. 37, No. 5, May 2002, pp. 657–661.) and 3 (P. Andreani et al., "Analysis and design of a 1.8-GHz CMOS LC quadrature VCO," IEEE Journal of Solid-State Circuits, vol. 37, No. 12, December 2002, pp. 1737–1747.) disclose an arrangement in which paired oscillators are connected with each other via MOS transistors.
However, the first conventional technique requires a VCO which runs at twice the desired frequency. On this account, the power consumption of the oscillator increases, and the circuit (flip flop circuit) design becomes complex.
Moreover, in the second and third conventional techniques and conventional techniques disclosed in Patent Documents 5 to 7, a large number of MOS transistors that are active elements are used for connecting two oscillator circuits with each other. On this account, noise (phase noise, etc.) is easily generated, and the power consumption increases. In addition, a circuit area increases.
Moreover, in the fourth conventional technique, the variable capacitors (varactors) and the transformers are used for connecting two oscillator circuits with each other. On this account, a circuit area increases, and the power consumption also increases.

Serially RC coupled quadrature oscillator


There is provided a light receiver including a photodiode converting an optical signal into an electrical signal, and a plurality of amplifiers respectively having different gains, each input end of the plurality of amplifiers being connected to one end of the photodiode, and one of the plurality of amplifiers being in operating state for outputting an output signal. At least one of the plurality of amplifiers and the photodiode are connected through a diode.

1. Field of the Invention
The present invention relates to a light receiver which is used for an optical pickup and has a photodiode as an input source and, particularly, to a light receiver with gain switching function.
2. Description of Related Art
An optical pickup is a device for reading and writing data on optical disks such as CD and DVD. The optical pickup typically includes a light receiver which receives reflected light from an optical disk as an optical signal by a photodiode, amplifies an electrical signal generated based on the optical signal and outputs the electrical signal.
Recently, highly functional light receivers are required so as to ensure application to optical pickups with multi-compatibility feature (e.g. CD-ROM, DVD-ROM, DVD-R, DVD-RAM, BD(Blu-ray disk)-ROM). In an optical pickup with multi-compatibility, a light receiver receives optical signals of different intensity levels, such as optical signals for writing/reading, optical signals with different wavelengths, and so on. Still, the light receiver needs to provide an output signal of a constant intensity level.
An optical pickup with multi-compatibility to receive optical signals with different wavelengths and different intensity levels can include a plurality of light receivers with different gains. However, this requires an optical system for inputting an optical signal to each light receiver and thus complicates the optical system of the optical pickup. Further, this hinders the miniaturization of the optical pickup. In addition, preparing a plurality of light receivers results in an increase in the number of components, which increases manufacturing costs.
To address the above drawback, an optical pickup can include a single photodiode and a plurality of amplifiers which have different gains as usage and are connected to the photodiode, so that one amplifier can be selected and activated according to need.
FIG. 3 is a circuit diagram of a light receiver 31 with multi-compatibility according to a related art. A cathode of a photodiode 1 which serves as an input signal source is connected to an input end of a first amplifier 4 and an input end of a second amplifier 3. The first amplifier 4 and the second amplifier 3 are negative-feedback amplifiers which have resistors R1 and R2, respectively, between the input and output. Outputs of the first amplifier 4 and the second amplifier 3 are input to an output circuit 7 through buffers 5 and 6, respectively. The light receiver 31 also includes a switching circuit 8 which switches to cause one of the first amplifier 4 and the second amplifier 3 to enter operating state and the other to enter non-operating state, alternately. The first amplifier 4 is used for processing DVD-R, and the second amplifier 4 is used for processing DVD-RAM, for example. When processing DVD-RAM, an optical signal reading speed is higher, and optical signal intensity is smaller because reflected light from the optical disk is lower than when processing DVD-R. Accordingly, parameters of circuit elements are set so that the second amplifier 3 has a higher gain and a wider bandwidth than the first amplifier 4.
In the light receiver 31 of FIG. 3, the first amplifier 4 and the second amplifier 3 are connected to the photodiode 1. The amplifier in the non-operating state affects the amplifier in the operating state as a load of resistance and capacitance, which leads to an increase in noise to cause an optical signal reading error. Particularly, the second amplifier 3 has a high gain and is largely affected by the first amplifier 4 as a load, and an optical signal reading error is likely to occur during operation of the second amplifier 3. Related arts are described in Japanese Unexamined Patent Application Publication Nos. 2003-22537 and 2005-32282.