The present invention is related to methods and apparatus for locating information related to a check drafter. In one embodiment, a communication is received indicating that a first check drafted by a drafter failed to clear. The communication includes an identifier. A first database transaction record is located using the identifier as a search key. The first database transaction record includes transaction information related to the first check, the transaction information including at least a first separate drafter identifier. At least the first separate drafter identifier is read from the first database record, and at least a portion of the first separate drafter identifier is provided to a first recipient.

1. Field of the Invention
The present invention relates to processing magnetic indicia, and in particular, to methods and apparatus for correlating magnetic indicia for or stored on financial instruments with database records.
2. Description of the Related Art
Checks are one of the most common forms of making non-cash payment. However, the processing of physical checks can be manually intensive. It has therefore become common for checks to be electronically processed using electronic check acceptance (ECA) systems. For example, when a customer makes a purchase at a merchant's point of sale terminal, the cashier scans the magnetic ink character recognition (MICR) data, typically in the form of characters or indicia printed at the bottom of a check, using a check reader terminal. The MICR characters typically include the customer's checking account number. In addition, the MICR characters can include the drawee bank's transit or routing number, and the check sequence number.
The cashier manually enters the check amount using the point of sale terminal. The cashier may also capture an image of the check. The checking account number, other MICR data, the check amount, and other transaction related information may be sent to a check processing service. The check processing service then submits the MICR data, including checking account number, check amount and other related information to a check clearinghouse, such as the Automated Clearing House Network (ACH), which provides for the inter-bank clearing of electronic payments for participating depository financial institutions. The customer and/or check processor may first have to give authorization to have the check converted to an electronic check for ACH use. The clearinghouse instructs the issuing bank on which the check is drawn to deposit the necessary funds in the merchant's bank. The customer's account is then debited for the amount of the check by the debited bank and the merchant's account in correspondingly credited by the merchant's bank.
Unfortunately, the customer's account may have insufficient funds to cover the check, the check may have been stopped, or the account may have been closed. In such instances, or for other problems, the check is returned as non-payable by the issuing bank. Using conventional techniques, it is often difficult and/or expensive to locate the customer so as to obtain payment in lieu of or to cover the check. This is particularly true for checks that have been processed using ECA systems as the check processing service often does not have an image of the check with the customer's personal information. The check processing service will merely be informed that the check has not been honored and will be provided with the MICR information of the dishonored check. The check processing service does not know the personal identity of the person who wrote the dishonored check in order to seek payment. Thus, checks often go uncollected, resulting in significant financial loses on the part of merchants or check guarantors.

Apparatus and methods for correlating magnetic indicia data with database records


A music diary processor for generating an electronic music diary. The music diary processor receives a plurality of event identifiers from a user, wherein each event identifier identifies a respective life event associated with the user. The user can also provide a date identifier identifying a date associated with the life event, a song identifier identifying one or more songs identified by the user as being associated with the live event. The event identifiers, song identifiers and the date identifiers are stored in an electronic storage medium wherein each song identifier and date identifier is coupled with at least one respective event identifier, and a plurality of event identifiers are coupled with each other. The music diary processor can serve as a music discovery vehicle, wherein the music diary processor can use data entered by a user to locate songs and other data associated with other music diaries.

People frequently associate, either consciously or subconsciously, music that was played during a past event, such as a high school graduation or a wedding, with one or more particular songs. When an individual hears such a song, even decades later, the individual may immediately recall favorable (or unfavorable) memories about the event. Moreover, as the individual listens to the song, the individual may also begin to remember other songs from the particular era that they enjoyed. People also frequently enjoy sharing aspects of their lives, including the music they listen to, with other individuals. This desire has been realized by a number of popular social networking sites devoted almost entirely to enabling users to share aspects of their lives with friends and other members of the site. As such, there is a need for a mechanism for facilitating music discovery in conjunction with past events and for the mechanism to be implemented in a manner that could be shared with friends, wherein the friends may be exposed to the past events and the music associated therewith.


The object of the present invention is to realize a method and a server which enable insertion of advertisement even in voice communication including multimedia communication. The server is configured as a server for managing PoC communication among multiple terminals, comprising: a right-to-speak management section for managing the right to speak of the multiple terminals; a data distribution section for transmitting and receiving data to and from the multiple terminals; and an advertisement control section for storing advertisement data and transmitting the stored advertisement data to the multiple terminals via the data distribution section.

1. Field of the Invention
The present invention relates to PoC (Push To Talk over Cellular) and extended-PoC communication system, and in particular to a method and a server which enable insertion of advertisements.
2. Description of the Related Art
PoC communication is communication using SIP (RFC 3216), which is an Internet protocol, and it enables communication among groups using a mobile phone network. The PoC communication is disclosed, for example, in Japanese Patent Laid-Open No. 2005-260973.
In a PoC communication system, there are multiple terminals connected to a PoC server to transmit and receive voice via half-duplex communication.
When transmission is performed, the terminal first requests the right to speak from the PoC server. The PoC server determines whether or not to approve the right to speak in a separately determined procedure. If the right to speak is to be approved, then it is issued to the terminal. Upon receiving the right to speak, the terminal transmits voice speech to the PoC server. To such terminals that do not have the right to speak, speech is transmitted from the PoC server. In this way, voice communication among multiple terminals is realized via half-duplex communication.
PoC can realize voice communication among two or more terminals by effectively utilizing a relatively narrow communication band, and it has attracted a lot of attention recently. International standardization of PoC is being promoted, and it is expected that PoC will become wide spread in the future. The result of PoC standardization activities by OMA (Open Mobile Alliance) is provided on the site: http://www.openmobilealliance.org/release_program/poc-v1—0.html.
A lot of services and content are provided free on the Web. For most of them, a business model called an advertisement model is adopted. This is a model for acquiring advertisement revenue by displaying advertisement on a part of the display area of a browser or by inserting advertisement copy in an e-mail, and there are various variations of this model.
However, this kind of advertisement model is hardly used in voice communication including telephone communication. Only a model in which a voice advertisement is inserted before the start of conversation has been implemented.
This is because determination of the position or the timing of inserting advertisement after start of the conversation is very difficult. Insertion after start of conversation may often interfere with the conversation itself, and as a result, the user feels uncomfortable, and the advertisement effect is negated. In the case of a model in which the advertisement is inserted at the beginning of a conversation, a problem occurs in that, when the conversation time becomes long, there will be a large gap between the benefit that the ad will created and the amount of advertisement.
An advertisement model is often effective for promoting of a service. However, in voice communication, there is a problem that the advertisement model has not been effectively utilized.

Method for inserting advertisement into PoC and extended-PoC communication system


Provided are a digitally controlled circulator and a radio frequency identification (RFID) reader having the circulator. A power splitter is composed of lumped elements and the values of the elements are digitally changed using switching means, in which the transmission loss of a signal is controlled according to whether the reader is in a transmission state or a reception state. Therefore, the loss can be minimized, and the circulator can be miniaturized and priced down by an integrated circuit (IC) semiconductor process and mounted in a mobile terminal such as a cellular phone.

1. Field of the Invention
The present invention relates to a circulator that is applied to a radio frequency (RF) transceiver system and a radio frequency identification (RFID) reader having the circulator, and more particularly, to a digitally controlled circulator that can be mounted in a small portable terminal such as a cellular phone and an RFID reader having the circulator.
2. Discussion of Related Art
RFID is a technology that reads information from a tag or writes information to a tag using an RF and is used to identify, trace and manage goods, animals, people and so forth to which a tag is attached. An RFID system based on the RFID technology comprises a tag or a transponder that has unique identification information and is attached to goods, people or so forth; a reader that reads the identification information from the tag or writes information to the tag; an object database; a network; and so forth.
Lately, an ultra high frequency (UHF) band RFID system is used to manage the distribution of goods. In addition, since an electronic product code (EPC) global generation-2 standard (refer to EPC Gen-2 standardization documents) and an international standardization organization (ISO) international standard are established as the standards of an air-interface for RFID, the UHF-band RFID system is expected to be extensively used, the EPC global generation-2 standard and ISO international standard aiming at assigning consistent unique codes to all goods mainly through an Auto-ID center.
FIGS. 1a and 1b are block diagrams illustrating a RFID reader used in conventional RFID system.
Referring to FIG. 1a, a signal carrying tag information is sent from a processor 100, which includes a microprocessor 101 and a memory 102, to a modem 104 through a bus line 103. The RF signal is sent to a transmitter 105 through the modem 104 and sent to a tag through an antenna 110. In addition, tag information that is received through the antenna 110 is sent to a receiver 106, and is sent to the processor 100 through the bus line 103 by the modem 104.
When the RF signal is sent from the transmitter 105 to the tag, a circulator 120 segregates the receiver 106 from the transmitter 105 to protect the receiver 106, the circulator 120 being disposed among the transmitter 105, the receiver 106, and the antenna 110.
Referring to FIG. 1b, the RFID reader has a structure in which an antenna 140 for sending an RF signal is separated from another antenna 141 for receiving an RF signal. A signal carrying tag information is sent from a processor 130 to a modem 134 through a bus line 133, the processor 130 consisting of a microprocessor 131 and a memory 132. The RF signal is sent to a transmitter 135 through the modem 134 and sent to a tag through the antenna 140. In addition, the tag information that is received through the antenna 141 is sent to a receiver 136, and is sent to the processor 130 through the bus line 103 by the modem 134.
The ferrite circulator 120 that operates as described above has excellent electrical performance. However, since the circulator 120 is made up of a great-sized magnetic material which cannot be fabricated by a general integrated circuit (IC) semiconductor process, it is not suitable for small, highly integrated, and inexpensive readers.
In addition, when the structure having the two antennas 140 and 141 as described above is applied to the system using a UHF band, dimensions occupied by the antennas increase, so that it is difficult to apply the structure to small devices such as cellular phones.
Therefore, in order to solve the problems, provided are an active circulator comprising transistors and a passive circulator based on a Wilkinson power splitter.
FIG. 2a shows an example of a conventional active circulator comprising transistors. In the active circulator, an antenna is connected to a first terminal P1 of a power splitter, and a signal that reflects from a tag and is received through the antenna is equally distributed to a second terminal P2 connected with a transmitter and a third terminal P3 connected with a receiver. Here, matching networks 210 and 220 are respectively connected with the second terminal P2 and the third terminal P3, and transistors T1 and T2 are respectively connected between the matching network 210 and the first terminal P1 and between the matching network 220 and the first terminal P1. The drain of the transistor T1 is connected with the first terminal P1 through a microstrip transmission line 201, the source of the transistor T1 is connected with the gate of the transistor T2 through a microstrip transmission line 202, and the gate of the transistor T2 is connected to a ground terminal through a microstrip transmission line 203.
FIG. 2b shows an example of a conventional passive circulator based on a Wilkinson power splitter. The passive circulator is a quasi-circulator including microstrip transmission lines on the basis of the principle of the Wilkinson power splitter.
An antenna is connected to a first terminal P1 of a power splitter, and a signal that reflects from a tag and is received through the antenna is equally distributed to a second terminal P2 connected to a transmitter and a third terminal P3 connected to a receiver and thus is transmitted. Here, a microstrip transmission line 230 is connected between the first terminal P1 and the second terminal P2, and a microstrip transmission line 231 is connected between the first terminal P1 and the third terminal P3.
The circulator that comprises only electronic devices as described above is easily integrated into a monolithic microwave integrated circuit (MMIC) or a radio frequency integrated circuit (RFIC). However, in the circulator comprising the transistors, the sensitivity of the receiver deteriorates due to noise generated at the transistors T1 and T2, and the transmitter barely processes a high output signal of more than 20 dBm without distortion due to a nonlinearity characteristic. Generally, when an active circulator is used, power can be transmitted without loss. However, it is known that the active circulator has worse characteristics than a passive circulator due to a very high noise figure (NF) (See "IEEE Trans. Microwave Theory and Tech.," G. Carchon and B. Nauwelaers, Vol. 48, No. 2, pp. 316-319, 2000).
Meanwhile, in the passive circulator based on the Wilkinson power splitter, electrical characteristics can be fixed by equivalent inductance and capacitance. The equal distribution of the signal received through the antenna to the transmitter and the receiver, however, causes an insertion loss of 3 dB. This insertion loss increases the NF, deteriorating receive sensitivity, and increases a bit error rate (BER). Therefore, the passive circulator based on the Wilkinson power splitter is difficult to apply to an RFID system requiring a very low BER.

Digitally controlled circulator and radio frequency identification reader having the same

Electronics and Telecommunications Research Institute


Disclosed is a sintering furnace comprising a furnace body and a lifting device, wherein the furnace body comprises a furnace chamber (10) and a furnace mouth (20), the furnace chamber (10) is connected with the furnace mouth (20), wherein the sintering furnace further comprises a sealing member (30) provided at the lifting device; when the sintering furnace is in a loading or unloading condition, the sealing member (30) blocks the furnace mouth (20). When the sintering furnace is in an unloading condition, the sealing member (30) can block the furnace mouth (20), the furnace chamber (10) does not contact with the outside directly, thus the temperature in the furnace chamber (10) will not drop sharply, and the service life of the sintering furnace will be increased.

Zirconia ceramic has high strength and a certain light transmittance, and has been widely used in zirconia restorations in prosthodontics. Zirconia restorations need to be sintered during their manufacturing processes.
The existing ceramic sintering device generally includes a furnace body and a lifting device. The furnace body includes a furnace chamber, a heating element and a furnace mouth, wherein the heating element is located in the furnace chamber for heating the furnace chamber and the furnace chamber is connected with the furnace mouth. When loading and unloading, the lifting device is detached from the furnace body to facilitate the loading and removal of sintered samples. When sintering, the lifting device is raised to a sintering position, and a sample to be sintered is fed into the furnace chamber through the furnace mouth for sintering.
In order to speed up the sintering process and reduce sintering time, the lifting device is usually quickly lowered to a loading position after the furnace chamber is pre-heated to a preset temperature; the lifting device is raised to the furnace chamber for sintering after zirconia restorations to be sintered are placed on the lifting device; after the sintering finishes, the lifting device is lowered to an unloading position, and the sintered samples are cooled down.
When the lifting device is lowered to the unloading position, the lifting device is completely detached from the furnace mouth, the furnace chamber is open, and thus the temperature drops sharply, which causes great damage to refractories and heating elements of the furnace chamber and reduces the service life. At the same time, since the temperature of the furnace chamber drops sharply, it takes a long time for the furnace chamber to be heated up again to the required temperature for sintering zirconia restorations. The whole sintering process generally takes 6 to 10 hours, which cannot achieve a rapid sintering process less than 20 minutes.


In some aspects of the invention, a zero current detecting circuit of a switching power supply device detects a gradient of the current flowing in an inductor in the OFF state of the switching element and detects the timing at which the current through the inductor becomes zero corresponding to the detected gradient of the inductor current. Specifically, the zero current detecting circuit receives a signal for controlling ON/OFF driving of the switching element and a voltage signal proportional to the current flowing through the inductor in an OFF state of the switching element. The voltage signal can be compared sequentially with first and second comparison reference voltages to control charging and discharging of a capacitor. Further, the zero current detecting circuit can detect a timing at which the charging and discharging voltage of the capacitor as the timing of zero current flowing through the inductor.

1. Field of the Invention
Embodiments of the invention relate to switching power supply devices that receive a rectified AC voltage and deliver a stable DC voltage.
2. Description of the Related Art
A power factor correction (PFC) converter of a step-up chopper type, a type of switching power supply device, generates a stable DC output voltage while generating an input current proportional to an input voltage utilizing self-excited oscillation of an inductor. The PFC converter has excellent characteristics including small-size, high efficiency, and production at a low cost. FIG. 4 shows a schematic construction of this type of switching power supply device, which is a power factor correction converter, in which the reference symbol BD designates a rectifier circuit that rectifies an AC power given from an AC power supply through an input filter F and delivers the rectified voltage to the switching power supply device.
This switching power supply device is provided with an inductor L connected to the rectifier circuit BD and a switching element Q that forms a current path from the rectifier circuit BD through the inductor L in the ON state of the switching element Q. The switching power supply device is further provided with a diode D that forms a current path between the inductor L and an output capacitor C2 in the OFF state of the switching element Q and a control circuit CONT that ON/OFF drives the switching element Q to control the current flowing through the inductor L. The symbol C1 designates an input capacitor.
The switching element Q provides the inductor L with a current proportional to the input voltage applied to the switching power supply device in the ON state of the switching element Q. The current flowing through the inductor L, inductor current, rises from zero over the ON period of the switching element Q. Upon turning OFF of the switching element Q, the voltage across the inductor L changes its polarity and the inductor current is delivered to the output capacitor C2 in the output side through the diode D. When the inductor current flowing out from the inductor L becomes zero, the switching element Q is turned ON again to transfer to the next operation cycle. This procedure is repeated. Japanese Unexamined Patent Application Publication No. 2010-220330 (also referred to herein as "Patent Document 1") and Japanese Unexamined Patent Application Publication No. 2011-103737 (also referred to herein as "Patent Document 2") disclose this kind of procedure.
The control circuit CONT for conducting the ON/OFF control of the switching element Q is a power supply driving IC to drive directly a MOS-FET used for the switching element Q. The control circuit CONT comprises an error detector 11 for detecting an error Comp (comparison reference voltage) that is a difference between an output voltage Vo detected by division with series-connected resistors R1 and R2, and a preset target output voltage. An ON width generating circuit 12 indicated in FIG. 4 generates a signal 'OFF' that determines an ON width Ton of the switching element Q, which is a MOS-FET, based on the error Comp detected by the error detector 11 and delivers the signal 'OFF' to a flip-flop 13 to reset the flip-flop.
The flip-flop 13 is set to make the output q thereof High and reset to make the output q Low. Receiving the output q from the flip-flop 13, a driving circuit 14 ON/OFF drives the switching element Q. Thus, the ON width generating circuit 12 resets the flip-flop 13 with the output signal 'OFF' to turn OFF the switching element Q.
The control circuit CONT comprises a zero current detecting circuit 15 that detects an inductor current Ir from a negative voltage developing across a resistor R3 inserted in a current path including the inductor L in particular in a power supply line at the negative side. The zero current detecting circuit 15 compares a voltage Vcs developing across the resistor R3 in proportion to the inductor current Ir with a preset reference voltage Vref, and delivers a zero current detecting signal Vzcd when the inductor current Ir reaches the zero level. The reference voltage Vref is set at as nearly to 0 mV as possible, but generally in the range of −10 mV to −5 mV in view of power supply noise and circuit parameter variation.
In order to turn ON the switching element Q at the timing of the lowest voltage, a valley of voltage, undergone by the switching element Q, the zero current detecting signal Vzcd delivered by the zero current detecting circuit 15 is delayed by a certain period of time Td in a delay circuit 16 and then given to the flip-flop 13 to set the flip-flop 13. Thus, the zero current detecting circuit 15 sets the flip-flop 13 with the zero current detecting signal Vzcd and turns ON the switching element Q.
The delay of the zero current detecting signal Vzcd in the delay circuit 16 is briefly described below. In the OFF state of the switching element Q, the switching element Q undergoes a high voltage developed at the inductor L, and the inductor current Ir decreases caused by flowing out of the current from the inductor L. When the inductor current Ir returns to the zero level, a critical point, the zero current detecting circuit 15 detects the zero level and delivers the zero current detecting signal Vzcd. The inductor current, however, swings further down to negative side due to resonant oscillation created by the inductance of the inductor L and a parasitic capacitance component in the circuit of the current path including the inductor L. The resonant oscillation also causes oscillation in the voltage undergone by the switching element Q. The voltage on the switching element Q is the lowest, a valley of voltage oscillation, at the moment when the inductor current Ir changes from a negative value to a positive value.
The delay circuit 16 delays the zero current detecting signal Vzcd after the zero current detection so as to turn ON the switching element Q at the timing of the lowest voltage, at a valley of the voltage resonant oscillation, undergone by the switching element Q. The delay time Td of the delay circuit 16 is fixedly set in general corresponding to the circuit parameters of the switching power supply device 1. Owing to the delay of the zero current detecting signal Vzcd performed in the delay circuit 16, switching loss on turning ON of the switching element Q is limited to the smallest and the surge current on turning ON of the switching element Q is also limited to the smallest.
The inductor current Ir varies with time corresponding to ON/OFF operation of the switching element Q. The rate of the variation, the gradient, depends on the input voltage Vi, the output voltage Vo, and the inductance of the inductor L, and other parameters in the circuit. The variation of the inductor current Ir also changes a rate of variation, a gradient, of the voltage Vcs, which is proportional to the inductor current Ir. As a result, even though the zero current detecting signal Vzcd is generated based on the comparison between the voltage Vcs and the reference voltage Vref, a discrepancy time Tzcd occurs, as shown in FIG. 5, between the timing at critical point arrival at which the inductor current Ir actually returns to zero from a negative value and the timing of the lowest voltage, the valley of voltage oscillation, on the switching element Q.
Because the inductor current Ir varies relating to an instantaneous value of the input voltage Vi varying with the phase as shown in FIG. 6, the discrepancy time Tzcd also varies with the input voltage Vi. At a specific example of phase A with a low input voltage Vi, the gradient of the voltage Vcs is large to make the discrepancy time Tzcd small. In contrast, at the phase D with a high input voltage Vi, the gradient of the voltage Vcs is small making the discrepancy time Tzcd large.
Despite this circumstance, the delay time Td is fixedly set in the delay circuit 16. As a consequence, at a phase of high input voltage Vi, for example, the switching element Q operates in a continuous mode. Further, even if the delay time Td for the zero current detecting signal Vzcd is adjusted so that the switching element Q is turned ON at the timing of the lowest voltage on the switching element Q, the switching element Q is turned ON at a timing earlier or later than the valley of voltage oscillation due to variation of the discrepancy time Tzcd. Therefore, the switching efficiency deteriorates and the power factor decreases. Thus, there exist certain shortcomings in the related art.

Switching power supply device, including a zero current detecting


A storage device such as a disk drive is provided with a lateral storage director. The lateral storage director is capable of self-assessing the status of the storage device. The lateral storage director also enables one storage device to transfer data files to another storage device over a communications link without the supervision of a host computer.

1. Field of the Invention
The present invention relates to a storage device such as a disk drive that has a lateral storage director which allows the storage device to communicate directly with other storage devices via a communications link.
2. Description of the Background Art
Storage devices such as disk drives, optical drives, flash memory, tape drives and the like are used to store most of the digital data in contemporary computer systems. Typically, optical and tape drives have slower access times and are therefore used for storing data which does not need to be accessed very frequently. Disk drives, having faster access times, are customarily used to store the data files which are more frequently required in data processing applications.
In larger computer systems there are typically groups of disk drives and other storage devices to accommodate storage requirements. The groups of disk drives may be organized into RAID groups in order to protect and recover the data if a single disk drive fails. In a small stand-alone computer there may be only one disk drive. However, increasingly, small computer systems have more than one disk drive or other storage device. A second disk drive may be used in a mirroring arrangement; or, a second disk drive may simply be available for use should the first disk drive become unavailable because of full utilization of capacity or a failure.
Disk drives and other storage devices are not commonly provided with significant self initiative. In most computer systems, the status of the disk drive, including remaining capacity and predictive failure functions, is learned by the host or a separate storage system controller after issuing a command to the disk drive. If the status of the disk drive indicates that some corrective action should be taken, then the host or storage system controller must initiate the action by issuing commands to the disk drive. This requires substantial computing resources to be used to manage storage device load balancing and storage device failure indicators.
What is needed is a storage device with the capability of recognizing the need for such tasks as load balancing and responding to predictive failure indicators. Furthermore, what is needed is a storage device which after recognition of the need for a task is capable of self initiating the task. Finally, what is needed is a storage device which can cooperate directly with another storage device over a communications link to transfer data files.

Storage device having a lateral storage director

Hitachi Global Storage Technologies Netherlands BV


The invention describes the use of water-insoluble esters with flash points above 80.degree. C., from monohydric alcohols of natural and/or synthetic origin with at least 4 carbon atoms, preferably at least 6 carbon atoms in the alcohol radicals, as the oil phase, or a constituent of the oil phase of invert drilling fluids which exist as W/O-emulsions, have a dispersed aqueous phase and ideally also have further usual additives in the continuous oil phase, which is fluid and pumpable in the temperature range of 0.degree. to 5.degree. C., and which are suitable for the environment-friendly development of, e.g., petroleum and natural gas deposits. Drilling fluids of the above type are also described which are characterized in that they contain as the continuous oil phase, or dissolved in ecologically-acceptable water-insoluble oils, an additive of at least largely water-insoluble ethers from monohydric alcohols, the oil phase in each case being fluid and pumpable in the temperature range of 0.degree. to 5.degree. C. and having flash points above 80.degree. C.

1. Field of the Invention
The invention discloses new drilling fluids and invert drilling muds based thereon, which are distinguished by high ecological acceptability and at the same time good storage and application properties. An important area of application for the new drilling fluid systems is in off-shore wells for the development of petroleum and/or natural gas deposits, the aim of the invention being particularly to make available industrially usable drilling fluids with high ecological acceptability. The use of the new drilling fluid systems has particular significance in the marine environment, but is not limited thereto. The new mud systems can be put to quite general use even in land-based drilling, for example, in geothermal wells, water bore-holes, in the drilling of geoscientific bores and in drilling for the mining industry. Here too it is essentially true that associated ecotoxic problems are substantially simplified by the ester-based drilling-oil fluids selected according to the invention.
2. Discussion of Related Art
Oil-base drilling fluids are generally used in the form of so-called invert-emulsion muds, which consist of a three-phase system: oil, water and finely particulate solids. These are preparations of the W/O-emulsion type, i.e. the aqueous phase is distributed as a heterogeneous fine dispersion in the continuous oil phase. A number of additives can be used to stabilize the system as a whole and to confer on it the desired application properties, particularly emulsifiers or emulsifier systems, weighting agents, fluid-loss additives, alkali reserves, viscosity regulators and the like. For details, refer, e.g., to the publication by P. A. Boyd et al. "New Base Oil Used in Low-Toxicity Oil Muds" Journal of Petroleum Technology, 1985, 137 to 142, and R. B. Bennett, "New Drilling Fluid Technology--Mineral Oil Mud" Journal of Petroleum Technology, 1984, 975 to 981 and the literature cited therein.
The importance of ester-based oil phases in reducing the problems created by such oil-base muds has been recognized for some time in the relevant field of technology. For example, U.S. Pat. Nos. 4,374,737 and 4,481,121 disclose oil-base drilling fluids in which non-polluting oils are to be used. The following are of equal value as the non-polluting oils--mineral oil fractions which are free from aromatic hydrocarbons, and vegetable oils, such as peanut oil, soybean oil, linseed oil, corn oil, rice oil or even oils of animal origin, such as whale oil. These named ester oils of vegetable and animal origin are all, without exception, triglycerides of natural fatty acids, which are known to be of high environment acceptability, and are clearly superior ecologically to hydrocarbon fractions--even when these do not contain aromatic hydrocarbons.
Interestingly enough, however, not one of the examples in the above U.S. patent specifications describes the use of such natural ester oils in invert-drilling fluids of this type. In every case, mineral oil fractions are used as the continuous oil phase. Oils of vegetable and/or animal origin are not considered for practical reasons. The rheological properties of such oil phases cannot be controlled over the wide temperature range generally required in practice, from 0.degree. to 5.degree. C. on the one hand, up to 250.degree. C. on the other.

Use of selected ethers of monofunctional alcohols in drilling fluids


A heat treatment apparatus for transferring a semiconductor wafer between a cassette and a boat and heat-treating a number of wafers loaded on the boat, comprising wafer holding assembly for supporting the wafer, and a plurality of posts for supporting the wafer holding assembly at predetermined intervals. The wafer holding assembly includes a ring member having an outside diameter larger than the diameter of the wafer and supported at a part of a peripheral portion thereof by the posts, and a plurality of supporting pieces provided onto the ring member, for supporting the wafer directly in contact with the wafer.

1. Field of the Invention
The present invention relates to a heat treatment apparatus having a wafer boat for heat-treating a semiconductor wafer, and more particularly, to an improvement of a boat for heat treatment adapted to be loaded in a vertical furnace.
2. Description of the Related Art
Since a vertical CVD apparatus is designed so that a wafer boat can be taken into or out from a process tube without touching the inner wall of the tube, it advantage, the apparatus of this type is conventionally used for the manufacture of a large scale integration semiconductor device, such as a VLSI.
In order to form a thin film with a uniform thickness on a large number of semiconductor wafers at a time, in a vertical furnace, a uniform flow of process gas must be produced with a minimum disturbance in the process tube.
In the vertical CVD furnace, in contrast with this, batch processing is executed, so that as many wafers as possible are expected to be processed at one time. Therefore, various components (supporting members and reinforcing members) of the wafer boat arrest a uniform gas flow in the process tube. Conventionally, there has been an attempt to improve the uniformity of wafer-surface film thickness during the film forming operation by variously changing the shape of the wafer boat.
Disclosed in Published Unexamined Japanese Patent Applications Nos. 58-108735 and 61-201695 is a wafer boat having a wafer loading disk whose diameter is larger than the wafer diameter. With use of this wafer boat, the deviation of wafer-surface film thickness can be decreased when phosphine (PH.sub.3) is added while a polysilicon film is being formed, and the film is finally doped with phosphorus to form a phosphorus-doped polysilicon film.
In a VLSI having a memory capacity of 1 to 4 megabits, however, the circuit pattern is so fine that it requires a high uniformity of wafer-surface film thickness. The aforesaid wafer boat cannot, however, fulfill this requirement. The larger the wafer diameter, in particular, the less uniform the film thickness at the peripheral edge portion of the wafer is liable to be. Modern wafers tend to switch from 6-inch versions to 8-inch versions, requiring effective measures to ensure the uniformity of wafer-surface film thickness.

Heat treatment apparatus having a wafer boat


This invention provides a method of improving a transplantation of hematopoietic cells from a donor to a recipient to treat a hematopoietic cell tumor in the recipient comprising immunizing the donor's hematopoietic cells with an antigen specific for the recipient's hematopoietic cell tumor, and transplanting the donor's immunized hematopoietic cells to the recipient. Also provided is a composition comprising purified hematopoietic cells primed to produce an immunological response to foreign tumor specific antigen. Also provided is a method of treating a tumor by the transplantation of hematopoietic cells from a donor to a recipient to treat the tumor in the recipient comprising immunizing the donor's hematopoietic cells with an antigen specific for the recipient's tumor, and transplanting the donor's immunized hematopoietic cells to the recipient.

The development of a vaccine against human malignancies has been a long-sought goal which has yet to be achieved. Many of the efforts toward this end have been frustrated by the lack of identification of a tumor-specific antigen which would allow tumor cells to be distinguished from normal cells. Conceptually, such an antigen could be used as a vaccine to induce the host's immune system to reject cells bearing that antigen.
Immunoglobulin (Ig) molecules are composed of heavy and light chains, which possess highly specific variable regions at their amino termini. The variable regions of heavy and light chains combine to form the unique antigen-recognition site of the Ig protein. These variable regions contain determinants (molecule shapes) that can themselves be recognized as antigens, or idiotypes (Id).
B-cell malignancies are composed of clonal proliferations of cells synthesizing a single antibody molecule with unique variable regions in the heavy and light chains. B-cell lymphomas and myelomas are neoplasms of mature lymphocytes which generally express and/or secrete synthesized Ig. The idiotypic determinants of the surface Ig of a B-cell lymphoma or myeloma can thus serve as a tumor-specific marker for the malignant clone.
Studies in experimental animals, as well as in man, have demonstrated the utility of the Ig idiotype as a tumor-specific antigen for the study of the biology of B-cell lymphoma in vitro and as a target for passive immunotherapy in vivo (1-3). Furthermore, active immunization against idiotypic determinants on malignant B-cells has been demonstrated to produce resistance to tumor growth in a number of syngeneic experimental tumor models, as well as specific anti-tumor therapy against established tumors (4-). Furthermore, preclinical studies in subhuman primates demonstrated that optimal immunization with human lymphoma-derived Id required conjugation of the protein to an immunogenic protein carrier (keyhole limpet hemocyanin (KLH)) and emulsification in an adjuvant (15). These results, taken together, provided the rationale for testing autologous tumor-derived idiotypic surface Ig (Id) as a therapeutic "vaccine" against human B-cell malignancies.
The mainstay of therapy for advanced stage myeloma patients with symptoms and signs of progressive disease remains systemic chemotherapy, particularly with alkylating agents and steroids. There is still some controversy regarding the superior efficacy of multiagent intensive chemotherapy regimens, such as the M2 or alternating combination chemotherapy regimens described by the Southwest Oncology Group and Medical Research Council, but most randomized trial results demonstrate only a modest incremental advantage in long-term overall survival compared with standard melphalan and prednisone, with no significant numbers of long-term disease-free survivors (16-23). Thus, although partial remissions of up to 60% are obtained with a variety of regimens, the median survival of about 30 months has remained constant for the last 30 years.
A more aggressive approach with intensive high dose chemoradiotherapy with either autologous or allogeneic bone marrow transplantation (BMT) is currently being explored by several groups of investigators. These protocols have improved initial response rates, although it remains to be seen whether these remissions are maintained with longer follow-up periods (24-28). Regardless of the initial responsiveness rates, the vast majority (>90%) of patients currently treated by these methods experience an eventual relapse of the tumor.
Many groups have described monoclonal B-cell populations in the peripheral blood as well as in the bone marrow of patients with myeloma, and these cells bear the myeloma protein idiotype on their surface as evidence of the clonal identity with the malignant plasma cells (29-37). As the removal of malignant plasma cells by chemotherapy does not appear to deplete the malignant stem cell (38), eradication of these precursor B-cells may ultimately be necessary for successful treatment of this disease.
The goal of the specific strategy described herein was to attempt to transfer tumor antigen-specific immunity induced in a bone marrow donor to a sibling BMT recipient with myeloma, as a means to enhance the therapeutic efficacy of allogeneic BMT. The transfer of induced antigen-specific humoral immunity to viral and other pathogens from immune donors has been explored in BMT patients as a potential therapeutic approach to the problem of increased host susceptibility to infection following the BMT procedure (39-42). A recent report also suggested the possible transfer of Varicella Zoster Virus specific cellular immunity from immune marrow donors to BMT recipients (43). This report, however, was inconclusive as to the origin of the cellular immunity response due to the immunization of both the donor and the recipient. Moreover, the literature reports that transfer of specific cellular immunity cannot be achieved in the context of transplantation (40).
Until this invention only a small percentage (<10%) of investigators had succeeded in eradicating a myeloma through BMT. This percentage is even smaller in the case of patients in the advanced stages of myeloma. The literature does not show that an immune response, and specifically a cellular immune response to a tumor specific antigen, could be transferred exclusively from an immunized donor in a BMT. Thus, donor immunization with myeloma Id represents a very important strategy for enhancing the specific anti-tumor effect of allogeneic marrow grafts.

Method and composition for transfer of active tumor-specific immunization from an immunized allogeneic bone marrow donor

The United States of America as represented by the Deptartment of Health and Human Services


An apparatus for supporting a liquid sample for measuring an intensity of X-ray radiation scattered by the liquid sample is configured such as to allow the X-ray radiation to impinge along a first direction (117, 217, 317, 417, 517, 617) through the first support member onto the liquid sample and to leave the liquid sample through the second member along a second direction (119, 219, 319, 419, 519, 619) different from the first direction to be detected by a detector. Further, a system for measuring an intensity of X-ray radiation scattered by a liquid sample and corresponding methods are provided.

The present invention relates to an apparatus and to a method for supporting a liquid sample for measuring an intensity of X-ray radiation scattered by the liquid sample. Further, the present invention relates to a system for measuring an intensity of X-ray radiation scattered by a liquid sample. In particular, the present invention relates to an apparatus and to a method for supporting a liquid sample for measuring an intensity of X-ray radiation scattered by the liquid sample, wherein the liquid sample is supported between two surfaces facing each other and supporting the liquid sample purely by a surface tension force. In particular, the electromagnetic radiation may be X-ray radiation, wherein, small angle X-ray scattering (SAXS), and/or wide angle X-ray scattering (WAXS) may be employed.
EP 1 477 796 A2 discloses a small angle X-ray scattering system with the X-ray beam oriented vertically for simplified analysis of liquid samples, wherein the sample is placed on a thin sample support, such as a piece of polyester film. Thereupon, the liquid sample is held and spreads naturally under the force of gravity.
The publication "High-Throughput Small Angle X-ray Scattering from Proteins in Solution Using a Microfluidic Front End", Analytical Chemistry, 2008, 80, 3648-3654, by K. N. Toft et al. discloses a microfluidic system with sample and buffer inlets, mixing channel and sample chamber for measuring small angle X-ray scattering from a sample placed in the sample chamber. Thereby, the sample chamber comprises polystyrene (PS) enclosing the sample completely. An advantage of the microfluidic device employed in a scattering experiment may be that the sample conditions may be modified in situ. On the other hand, the surface to volume ratio is big resulting in a strong interference of a signal from the channel walls with a signal from the sample. In particular, the sample may be deposited or may sediment on the walls of the microfluidic device and may change the real concentration of the constituents of the sample (which may partially adhere to the channel walls of the microfluidic device). Moreover, in most cases filling of the channels requires pumping the fluid sample involving applying a shear stress to the sample. This may perturb or even damage especially a biological sample.
Alternatively, a liquid sample may be placed into a standard array of wells or of capillaries with an automatic sample changer for measuring X-ray scattering data. Typically, these automatic sample changers manipulate volumes of sample which are bigger than 1 μl or even bigger than 10 μl. Moreover, using syringes presents the same problems as the pumping of the sample when using microfluidic devices: The sample is subjected to shear stress with the risk of damaging or at least modifying the sample, in particular a sensible biological sample. Further, the true concentration of constituents, such as proteins, in the sample may be changed due to specific adsorption of specific constituents to a well wall or to a wall of a syringe.
There may be a need for an apparatus and for a method for supporting a liquid sample for measuring an intensity of X-ray radiation scattered by the liquid sample which allows very small sample volumes, such as in the microliter or nanoliter range, which reduces a contact area between a support and the sample, which reduces shear forces experienced by the sample, which reduces sample loss, which allows a fast measurement, which allows easy cleaning of the support and/or which allows easy coupling with an automatic sample changer.
Further, there may be a need for a system for measuring an intensity of X-ray radiation scattered by a liquid sample providing at least one of the above-mentioned advantages.

Apparatus and method for supporting a liquid sample for measuring scattering of electromagnetic radiation


Copolymers are disclosed of lower alpha-olefins and HALS-containing monomers, typically 1-(10-undecenyl)-2,2,6,6-tetramethylpiperidine. They may be used for light or heat stabilizing, by themselves or in blends with other polymers.

Prior to the present invention, it has been an important objective in the polyolefin industry to develop polyolefins which are resistant to thermal degradation and the degradation caused by exposure to light and ultraviolet rays. Various kinds of hindered amines--"hindered amine light stabilizers" ("HALS")--have been widely used for these purposes. They have been found to be effective in stabilizing against light when blended into the polyolefin, but migration and leaching out by the relatively mobile hindered amines can result in reduced effects against light. On the other hand, oligomeric hindered amine light stabilizers, such as Chimassorb 944 and the like, generally do not migrate or leach out. But these stabilizers have been found to be less effective in stabilizing against light, compared with relatively mobile hindered amine light stabilizers. Furthermore, since currently commercially available HALS can not adequately protect against heat, thermal stabilizers have to be added. Many commonly used HALS, however, show negative synergy with the most widely used class of thermal stabilizers, phenolic antioxidants. It would be highly desirable to have a light stabilizer which does not show negative synergy with phenolic stabilizers at high temperatures. Thus the art is constantly looking for improved methods of protecting polyolefins and polyolefin products from degradation caused by light and heat.
So far as we are aware, a practical copolymer of propylene or other alpha-olefin has not been made with a comonomer containing an effective hindered amine light stabilizer as a structural unit, hereinafter sometimes called HALS comonomer. Such a copolymer would be highly desirable not only for medical applications as mentioned above, but for other applications of polypropylene which require resistance to degradation from heat and visible light. Some types of medical products would benefit from protection against degradation caused by repeated autoclaving. Such copolymers containing relatively low concentrations of HALS comonomers could be used by themselves and would be expected to withstand the conditions of injection molding; similar copolymers, perhaps containing higher concentrations of HALS comonomers, could be blended with less expensive propylene homopolymers, and would not migrate as the unattached hindered amines have been known to do.
In U.S. Pat. No. 3,975,357, Murayama et. al. describe a large class of N-substituted 2,2,6,6-tetramethylpiperidines which may be used as heat and light stabilizers. The described class includes compounds of the formula ##STR1## where R.sup.1, R.sup.2, R.sup.3 and R.sup.4 can be methyl and R.sup.5 can be an alkenyl group of 3-10 carbon atoms. No attempt was made to copolymerize them, however; they were simply blended with a host polymer to stabilize it, in a manner no different than many other unpolymerizable stabilizer additives.
In U.S. Pat. Nos. 4,857,595 and 4,975,489, Kazmierzak and MacLeay describe "polymer-bound" hindered amine light stabilizers. The polymers are made to contain hindered amines by reacting hydrazido substituted hindered amines with, for example, maleic anhydride modified polypropylene. Similar reactions are described by MacLeay and Myers in U.S. Pat. Nos. 4,683,999 and 4,868,246. One must first make the maleic anhydride-modified resin, however, an expensive separate step which tends itself to degrade polypropylene or other thermoplastics. While the HALS-containing moiety is polymer-bound, it is not incorporated in the polymer backbone by original copolymerization. See also German patent 4,436,355 to Bartus et al (Chemie Linz) and U.S. Pat. No. 4,473,657 to Rekers et al (Deering Milliken) which use HALS maleimides to combine in a reactor/extruder with preformed polymers, making grafted polymer-bound hindered amine light stabilizers. These materials also do not employ the HALS component as an original comonomer with the propylene or other original .alpha.-olefin monomer.
Other types of grafting attempts are described in Japanese JP Kokai 25330/94. Grafting onto functional groups such as aldehyde groups has definite disadvantages, such as low yields associated with undesirable unreacted monomer, and degradation of the physical properties of the base polymer.
Sevini and Noristi, in U.S. Pat. No. 4,960,593, propose the intimate incorporation of free hindered amines in polypropylene by including them in the polymerization reaction mixture at the time of initiation of the reaction, or sometime during the course of the reaction, or afterwards but before the catalyst is quenched. As stated at the end of their Example 10, the timing of the addition is not critical; the inventors perceive no difference so long as the HALS compound is introduced before the catalyst is quenched. Thus, in spite of the fact that their vastly comprehensive general formulas include compounds employed in the present invention, it is clear that the patentees do not intend to copolymerize them; in fact, all but a few of their HALS compounds could not possibly copolymerize, being without polymerizable functional groups. The HALS compounds are simply incorporated into the mixture in perhaps a more intimate manner than has been the case for more conventional polyolefins in which the HALS compound is blended after the catalyst is quenched. Neither this patent nor any other of which we are aware discloses a copolymer of propylene with a copolymerizable hindered tertiary amine compound of the formula (I) below.
We are aware of the work of Wilen, Markku, Auer and Nasman, J. Polymer Sci., Part A-Polymer Chemistry, v 30, 1163-1170 (1992), who copolymerized certain hindered secondary amines with propylene. The polymerizable group was attached to the 4-position of the piperidine group, such as in 4-(hex-5-enyl)-2,2,6,6-tetramethylpiperidine. Because this reactant is a secondary amine, i.e. the 1-position is >NH, polymerization catalytic activity is drastically reduced and can only be restored by using excessively large amounts of triethyl aluminum (TEA); multiple reactions are needed to obtain significant yields. We use hindered amines, by contrast, in which the polymerizable group is at the 1-position of the piperidine group, making the amine a tertiary amine.
Langer and Haynes, in U.S. Pat. No. 3,755,279, use as comonomers 1-alkenylpiperidines which are hindered only enough to avoid destruction of the polymerization catalyst, yet the amine sites can be used for dyeing. The 2- and 6-positions of the piperidine are occupied by only one alkyl group each. These compounds are not highly hindered around the nitrogen atom and their efficacy as a light stabilizers is expected to be much less than our comonomers. The present application is concerned particularly with 1-alkenyl piperidines wherein the 2- and 6- positions are fully substituted to develop the light and heat stabilization.

Copolymers of propylene with polymerizable hindered amine light stabilizers


A rotation stopped detection sensor detects a rotation stopped condition of a rotatable body using a plurality of optical sensors. The detection sensor also includes a rotation disk having optical guide portions for guiding light beams from light emitting devices to respective light receiving devices, and light shut off portions for shutting off the light beams to the respective light receiving devices. The optical guide portions and the light shut off portions are disposed alternately on an outer peripheral portion of the rotation disk. The plurality of optical sensors are disposed such that when the disk is stopped, one of the optical sensors is always at a position corresponding to an optical guide portion. As a result, when the disk is stopped, there is always one output from the optical sensors which is at a high level. Hence the stopping of the disk can be advised using a direct output from the optical sensor.

A conventional rotation detection sensor for detecting a rotation stopped condition of a rotatable body using a light beam comprises a single optical sensor and a rotatable disk (referred to hereunder simply as a disk) with an outer peripheral portion thereof having approximately equal width transparent portions which pass a light beam and opaque portions which do not pass a light beam. The optical sensor has a light source which generates an AC light beam by means of an AC signal from a signal generator, and a light receiving element for receiving the light beam from the light source, positioned facing each other on opposite sides of the outer peripheral portion of the disk, and generates from an output circuit, an output signal corresponding to a light received output from the light receiving element.
With such a construction, when the disk is rotating, the transparent portions and the opaque portions alternately intersect the light beam. Since the widths of the transparent portions and the opaque portions are approximately the same, then the output from the light receiving element of the optical sensor has an output form with a high level condition and a low level condition appearing alternately at approximately even interval following to the passing of the transparent portions and the opaque portions with rotation of the disk. Since the light source is driven by an AC signal from the signal generator, then in the case where the signal frequency of the signal generator is substantially higher than the rotational speed of the disk, the output signal from the optical sensor in the high level interval where the light beam is received, becomes an AC signal which is switched at the signal frequency of the signal generator.
When the disk stops rotating, then either a transparent portion or an opaque portion is positioned in the optical path of the light beam. Consequently, the output condition of the optical sensor is fixed at either a high level condition or a low level condition.
In this arrangement, when the disk stops rotating, an indicator lamp is illuminated, for example, for advising personnel that the vicinity of the disk is "not dangerous". In order to illuminate the indicator lamp with an output signal from the optical sensor, when the disk has stopped, a light beam is passed so that the output signal from the optical sensor becomes a high level condition, the indicator lamp can be illuminated directly by the output energy from the optical sensor. However, the disk will not always stop at a position where the light beam is passed. In the case where the disk stops at a position where the light beam is shut off, then the indicator lamp cannot be illuminated directly by the output signal from the optical sensor.
Therefore, it has been proposed that a rotation detection sensor has two indicator lamps, one having the output signal from the optical sensor input directly thereto, and the other having the output signal from the optical sensor input via a NOT circuit thereto, so that when the disk stops, one or the other of the two indicator lamps is continuously illuminated. In this case, when the disk is rotating the two indicator lamps flash alternately.
It has also been proposed that a rotation detection sensor has a circuit configuration with a single indicator lamp, which is devised such that the indicator lamp is continuously illuminated when the disk stops.
More specifically, the circuit configuration is such that a light received output from an optical sensor is rectified by a rectifying circuit, and a rectified output therefrom is then input to an on-delay circuit via a NOT circuit. An indicator lamp is then illuminated by an output from the on-delay circuit. The rectifying circuit in this case is a device for rectifying the envelope of the AC output signal from the optical sensor which is based on the passing and shut off of the light beam due to rotation of the disk. It has no rectifying function with respect to the AC signal having the frequency of the signal generator. That is to say, the envelope of the AC output signal from the optical sensor due to the passing of the transparent and opaque portions of the rotatable disk is treated as the AC signal, and this AC signal is rectified by the rectifying circuit.
In this way, whether the disk stops in a condition such that the light beam is received by the light receiving element via a transparent portion, or stops in a condition where the light beam is shut off by an opaque portion, once stopped, the output condition from the optical sensor is fixed and hence does not become alternating. Consequently, since if the disk is stopped, the rectified output from the rectifying circuit is always at a zero level, and the output signal from the NOT circuit is thus always a high level, then the indicator lamp can be illuminated after a predetermined time lapse by the output from the on-delay circuit.
However, with either of the abovementioned circuit configurations, the function of the NOT operation carried out by the NOT circuit is indispensable for illumination of the indicator lamp when the disk is stopped. Therefore the following problems arise.
In the case where the transparent portions of the disk become soiled, there is the possibility that even when a transparent portion intersects the light beam, light is not received by the light receiving element. In this case, the light received output level of the optical sensor will remain at a low level condition even if the disk is rotating. The indicator lamp to which the signal is input via the NOT circuit will therefore be continuously illuminated, indicating that the disk is stopped (rotation stopped) even though the disk may still be rotating. This situation can arise not only in the abovementioned case where the transparent portions become soiled. For example, the same can also occur in the case where the light source malfunctions so that light is not produced, or the light receiving element malfunctions so that light cannot be converted to an electrical signal, or the light source or light receiving element attachment becomes disconnected (in the case where the light receiving element is provided independent of the output circuit).
The present invention takes into consideration the above situations with the object of providing a rotation detection sensor which can advise of a rotatable body stopped condition by for example illumination of an indicator lamp, without using a NOT circuit to carry out a NOT operation on the output signal from the optical sensor.


A storage system includes a group of storage devices which include back-up devices configured to assure appropriate response time. When a data request from a host computer arrives, and the number of failed devices has changed as shown by a device state management table, a determination is made regarding the number of devices from which to read data. This determination is made based on an indication of redundancy which indicates how many of the disk devices are allowed to be in a failed state at the time of data reading. Typically, the indication of redundancy is determined by the sum of the number of failed devices and a predetermined number. The determined number of devices are selected in accordance with a selection factor, and a selection result is written into a disk management table. Then, the reading process is executed with respect to the target disk devices.

The present invention relates to a storage system including a plurality of storage devices with the interrelationship established thereamong for data recovery, and a data reading method and a data reading program regarding the same.
A storage system recently developed is a type operating a plurality of magnetic disk devices in parallel, so that a data reading/writing process requested by a host is increased in speed, and the reliability is improved with the redundant structure. Such a storage system is generally referred to as RAID (Redundant Arrays of Inexpensive Disks). The RAID structure varies in level, i.e., level 1 to level 5, details of which are described in Non-patent Document 1 below.
In Non-patent Document 2, described is another type of RAID structure derived by expanding the RAID structure of level 4 of Non-patent Document 1. The RAID structure is the one offering a guarantee of data storage even if any two disk devices fail. Specifically, for guaranteeing as such, used are two types of parity data: one is parity data as a calculation result of exclusive OR of data stored in the respective storage devices forming a logical unit; and the other is parity data as a calculation result of exclusive OR of data and a multiplied value of the other parity data and a specific coefficient.
In the storage system, other than a Fibre Channel disk device, an ATA (AT attachment) disk device is getting popular. The problem is that an ATA disk device is lower in cost than a Fibre Channel disk device, but also lower in reliability and thus fails easily. Thus, it is highly possible that any two disk devices fail at the same time, i.e., double failure occurs. Moreover, the capacity per disk device has been steadily increasing, resulting in longer time taken for data recovery in any failed disk device utilizing the RAID technology. Thus, even if any high-reliable disk devices are in use, the possibility of double failure remains high. In consideration thereof, as the technology of Non-patent Document 2, measures to be taken against multiple failures will become increasingly important from now on.
In Patent Document 1, described is a storage system offering a guarantee of response time with respect to a data request coming from a host even if any failure occurs to disk devices. With this storage system, no matter if any failure is occurring to disk devices, any other data needed for recovering the requested data is always read in parallel. Even if reading of the requested data does not work, the requested data is favorably recovered without newly reading redundant data from the disk devices.
Herein, Non-patent Document 1 is "a Case for Redundant Arrays of Inexpensive Disks (RAID)" authored by D. Patterson, proceedings of the 1988 ACM SIGMOD international conference ON Management of data, PP. 109 to 116, 1988.
Non-patent Document 2 is "EVENODD: an Optimal Scheme for Tolerating Double DISK Failures in RAID Architectures" authored by M. Blaum, Proceedings of the 21st Annual International Symposium ON Computer Architecture, PP. 245 to 254, 1994.
Further, Patent Document 1 is JP-A-10-247133.

Storage system for increased cache reliability via reading redundant disks into cache


A stretch blow molding system that condition preforms such that the temperature distribution within the cross-section of each preform is optimized prior to blow molding operations is provided. The system has a temperature measurement and control system capable of directly monitoring both the outside as well as inside surface temperature of preforms at different stages of transport throughout the thermal conditioning section of the system.

This invention is directed to blow molding systems. More specifically, it is directed to stretch blow molding systems that condition preforms such that the temperature distribution within the cross-section of each preform is optimized prior to blow molding operations.
By way of background, one of the most critical process variables when attempting to stretch blow mold certain materials is the temperature distribution of the preform as it is being blown. This variable often has a significant impact on the most important physical properties of the final blown article. Ideally, the preform wall cross-sectional temperature distribution should be optimized for blow molding operations. In addition, it is advantageous within an automated blow molding process if preforms that are moving through the system are consistent in temperature profile, one preform to the next. In more specific terms, it is advantageous for both the inside and outside surface temperature of the preforms to be equal to each other and at the preferred blow molding temperature of the material.
The following collection of U.S. patents, all of which are incorporated herein by this reference, describe the current state-of-the-art associated with the thermal conditioning of preform blanks prior to automated blow molding operations:                U.S. Pat. No. 4,079,104        U.S. Pat. No. 5,066,222        U.S. Pat. No. 5,322,651        U.S. Pat. No. 5,607,706
These patents collectively teach the following: 1) the use of infrared radiation to raise the temperature of a series of dynamically conveyed preforms to a transition temperature wherein blow molding operations are enabled and optimized, 2) the qualitative time-varying temperature behavior of both the outside as well as the inside of a preform when it is subjected to infrared radiation from the outside of the preform, 3) the benefit of using forced air cooling on the outside of the preform to enable the inside preform surface temperature to "catch-up" with the outside temperature, 4) the benefit of thermally pre-conditioning preform blanks prior to the infrared radiation re-heat cycle to compensate for preform-to-preform ambient thermal differences, 5) the practice of using pyrometers to provide some degree of average outside surface temperature information for the purpose of process control, and 6) the benefit of rotating the preforms on their axis as infrared radiation is applied to more uniformly deliver thermal energy prior to blow molding operations.
However, there is a need in the field to accurately determine and control both the outside and inside surface temperature of preforms as such items enter the blow molding operation. The state-of-the-art implementations, as described in, for example, the noted patents, are limited to providing an averaged automated process control measurement on the outside surface temperature of the preform, exclusively. Process information related to critical control parameters (e,g., inside and outside preform temperature) has been limited in scope due to existing limitations in infrared temperature measurement technology and methodology.
For example, in existing state-of-the-art implementations, the outside surface temperatures of preforms are measured using a pyrometer. Pyrometers are well known in the art and can perform accurate quantitative temperature measurements of objects placed within their field of view (FOV). A significant limitation of pyrometers, though, is that their response time is relatively slow. To obtain an accurate temperature measurement using a pyrometer, the object under test needs to remain in the pyrometer's field of view (FOV) for a period of time ranging from hundreds of milliseconds to seconds. In a dynamic blow molding system, the rate at which preforms are transported through the system does not allow for the accurate temperature measurement of any one preform using a pyrometer. Rather, state-of-the-art implementations use pyrometers to obtain an average surface temperature of the last several preforms passed through the system. One limitation of this sampling scheme is that significant preform to preform temperature variations, if present, are averaged out and go undetected by the process control apparatus deployed in prior art machines.
At the speeds at which preforms are transported through existing state-of-the-art machines, temperature measurement must be made within a couple of milliseconds—before the part moves out of the sensing device's field of view (FOV). This time period is much too short to allow pyrometers to make an accurate temperature measurement. Direct contact methods for measuring temperatures, such as thermocouples, are impractical because of speed limitations and because such devices may cause damage to the hot pliable preform. If such damage occurred, it would undesirably render the process a high maintenance endeavor.
An additional and perhaps more severe limitation related to the slow response time of pyrometers is that that there has been no direct practical manner discovered by which a reasonable and accurate measurement of the inside surface temperature of moving preforms can be obtained using these devices. The inside surface temperature of a preform 10 can only be directly measured through the open end of the preform. Indirect methods, using complex thermal conduction equations and multiple, time spaced pyrometers, have been theorized but have not been implemented into factory production systems. The difficulty of implementing, maintaining, and calibrating such systems is a serious drawback. Further, such systems only predict from indirect measurements—which allows uncontrolled environmental and other variables to adversely affect the temperature estimates and create inaccuracy and mistrust of such estimates.
The present invention, however, overcomes these difficulties and others.

Method and apparatus for the measurement and control of both the inside and outside surface temperature of thermoplastic preforms during stretch blow molding operations


An oil well cuttings disposal tank apparatus of improved construction provides a tank body having an interior and a plurality of side walls, a plurality of end walls, a bottom wall, and a top wall with a discharge opening at one end portion thereof. The discharge opening communicates with the intersection of the top wall and one of the end walls. A hatch is provided for opening and closing the discharge opening. A plurality of lifting plates are attached to the side walls and extend upwardly from the top wall, each of the lifting plates having openings or eyelets for attaching lifting lines thereto. A stacking beam is associated with each lifting plate, each stacking beam extending from the top wall upwardly a distance and attaching to the lifting plate at a position above the top wall. Each stacking beam has a load bearing surface that extends laterally from its lifting plate inwardly toward an opposite stacking beam and the central portion of the tank. A pair of slots on the lower end portion of the tank body at the bottom wall are provided, the slots being shaped to conform to and nest upon the bearing surfaces of the stacking beams when one tank body is nested upon another similarly configured tank body. Upper portions of the lifting plates prevents sliding of one tank relative to the other tank in a "X" direction. The connection between stacking beams and lateral slots prevent sliding of one tank stacked upon another tank in a "Y" direction.

1. Field of the Invention
The present invention relates to the disposal of the cuttings from oil and gas well drilling, and more particularly to an improved method and apparatus for the disposal of cuttings generated during drilling of an oil and gas well. More particularly, the present invention relates to an improved cuttings tank apparatus useful in the disposal of cuttings generated during the drilling of an oil and gas well wherein an improved configuration enhances the storage of cuttings at a well drilling site or rig with limited space and also facilitates quick emptying of the tank at a selected approved disposal site.
2. General Background of the Invention
In the drilling of oil and gas wells, a drill bit is used to dig many thousands of feet into the earth's crust. Oil rigs typically employ a derrick that extends above the well drilling platform and which can support joint after joint of drill pipe connected end to end during the drilling operation. As the drill bit is pushed farther and farther into the earth, additional pipe joints are added to the ever lengthening "string" or "drill string". The drill pipe or drill string thus comprises a plurality of joints of pipe, each of which has an internal, longitudinally extending bore for carrying fluid drilling mud from the well drilling platform through the drill string and to a drill bit supported at the lower or distal end of the drill string.
Drilling mud lubricates the drill bit and carries away well cuttings generated by the drill bit as it digs deeper. The cuttings are carried in a return flow stream of drilling mud through the well annulus and back to the well drilling platform at the earth's surface. When the drilling mud reaches the surface, it is contaminated with small pieces of shale and rock which are known in the industry as well cuttings or drill cuttings.
Well cuttings have in the past been separated from the reusable drilling mud with commercially available separators that are know as "shale shakers". Some shale shakers are designed to filter coarse material from the drilling mud while other shale shakers are designed to remove finer particles from the well drilling mud. After separating well cuttings therefrom, the drilling mud is returned to a mud pit where it can be supplemented and/or treated prior to transmission back into the well bore via the drill string and to the drill bit to repeat the process.
The disposal of the separated shale and cuttings is a complex environmental problem. Drill cuttings contain not only the mud product which would contaminate the surrounding environment, but also can contain oil that is particularly hazardous to the environment, especially when drilling in a marine environment.
In the Gulf of Mexico for example, there are hundreds of drilling platforms that drill for oil and gas by drilling into the subsea floor. These drilling platforms can be in many hundreds of feet of water. In such a marine environment, the water is typically crystal clear and filled with marine life that cannot tolerate the disposal of drill cuttings waste such as that containing a combination of shale, drilling mud, oil, and the like. Therefore, there is a need for a simple, yet workable solution to the problem of disposing of oil and gas well cuttings in an offshore marine environment and in other fragile environments where oil and gas well drilling occurs.
Traditional methods of cuttings disposal have been dumping, bucket transport, cumbersome conveyor belts, and washing techniques that require large amounts of water. Adding water creates additional problems of added volume and bulk, messiness, and transport problems. Installing conveyors requires major modification to the rig area and involves many installation hours and very high cost.
Safeguard Disposal Systems, Inc. of Lafayette, La. has manufactured, sold, and used publicly a cuttings disposal tank that includes hatch openings into which oil well cuttings can be placed. These prior art tanks also have attachments for enabling lift lines to be affixed to the tank so that it can be transported to and from offshore platforms and emptied when full. Further examples of these tanks are shown in one or more of the following U.S. Pat. Nos.: 5,564,509; 5,402,857; Des. 337,809; and Des. 296,027. U.S. Pat. Nos. 5,564,509 and 5,402,857 are incorporated herein by reference.


The present invention is directed to compositions of matter useful for the treatment of hematopoietic tumor in mammals and to methods of using those compositions of matter for the same.

Malignant tumors (cancers) are the second leading cause of death in the United States, after heart disease (Boring et al., CA Cancel J. Clin. 43:7 (1993)). Cancer is characterized by the increase in the number of abnormal, or neoplastic, cells derived from a normal tissue which proliferate to form a tumor mass, the invasion of adjacent tissues by these neoplastic tumor cells, and the generation of malignant cells which eventually spread via the blood or lymphatic system to regional lymph nodes and to distant sites via a process called metastasis. In a cancerous state, a cell proliferates under conditions in which normal cells would not grow. Cancer manifests itself in a wide variety of forms, characterized by different degrees of invasiveness and aggressiveness.
Cancers which involve cells generated during hematopoiesis, a process by which cellular elements of blood, such as lymphocytes, leukocytes, platelets, erythrocytes and natural killer cells are generated are referred to as hematopoietic cancers. Lymphocytes which can be found in blood and lymphatic tissue and are critical for immune response are categorized into two main classes of lymphocytes: B lymphocytes (B cells) and T lymphocytes (T cells), which mediate humoral and cell mediated immunity, respectively.
B cells mature within the bone marrow and leave the marrow expressing an antigen-binding antibody on their cell surface. When a naive B cell first encounters the antigen for which its membrane-bound antibody is specific, the cell begins to divide rapidly and its progeny differentiate into memory B cells and effector cells called "plasma cells". Memory B cells have a longer life span and continue to express membrane-bound antibody with the same specificity as the original parent cell. Plasma cells do not produce membrane-bound antibody but instead produce the antibody in a form that can be secreted. Secreted antibodies are the major effector molecule of humoral immunity.
B cell-related disorders include, but are not limited to, malignant lymphoma (Non-Hodgkin's Lymphoma, NHL), multiple myeloma (MM) and chronic lymphocytic leukemia (CLL, B cell leukemia (CD5+ B lymphocytes). Non-Hodgkin's lymphomas (NHLs), a heterogeneous group of cancers principally arising from B lymphocytes, represent approximately 4% of all newly diagnosed cancers (Jemal, A. et al., CA-Cancer J Clin., 52: 23-47 (2002)). Aggressive NHL comprises approximately 30-40% of adult NHL (Harris, N. L. et al., Hematol. J., 1:53-66 (2001)) and includes diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma (MCL), peripheral T-cell lymphoma, and anaplastic large cell lymphoma. Frontline combination chemotherapy cures less than half of the patients with aggressive NHL, and most patients eventually succumb to their disease (Fischer, R. I., Semin. Oncol., 27 (suppl 12): 2-8 (2000)).
T cells mature within the thymus which provides an environment for the proliferation and differentiation of immature T cells. During T cell maturation, the T cells undergo the gene rearrangements that produce the T-cell receptor and the positive and negative selection which helps determine the cell-surface phenotype of the mature T cell. Characteristic cell surface markers of mature T cells are the CD3:T-cell receptor complex and one of the coreceptors, CD4 or CD8.
In attempts to discover effective cellular targets for cancer therapy, researchers have sought to identify transmembrane or otherwise membrane-associated polypeptides that are specifically expressed on the surface of one or more particular type(s) of cancer cell as compared to on one or more normal non-cancerous cell(s). Often, such membrane-associated polypeptides are more abundantly expressed on the surface of the cancer cells as compared to on the surface of the non-cancerous cells. The identification of such tumor-associated cell surface antigen polypeptides has given rise to the ability to specifically target cancer cells for destruction via antibody-based therapies. In this regard, it is noted that antibody-based therapy has proved very effective in the treatment of certain cancers. For example, HERCEPTIN® and RITUXAN® (both from Genentech Inc., South San Francisco, Calif.) are antibodies that have been used successfully to treat breast cancer and non-Hodgkin's lymphoma, respectively. More specifically, HERCEPTIN® is a recombinant DNA-derived humanized monoclonal antibody that selectively binds to the extracellular domain of the human epidermal growth factor receptor 2 (HER2) proto-oncogene. HER2 protein overexpression is observed in 25-30% of primary breast cancers. RITUXAN® is a genetically engineered chimeric murine/human monoclonal antibody directed against the CD20 antigen found on the surface of normal and malignant B lymphocytes. Both these antibodies are recombinantly produced in CHO cells.
In other attempts to discover effective cellular targets for cancer therapy, researchers have sought to identify (1) non-membrane-associated polypeptides that are specifically produced by one or more particular type(s) of cancer cell(s) as compared to by one or more particular type(s) of non-cancerous normal cell(s), (2) polypeptides that are produced by cancer cells at an expression level that is significantly higher than that of one or more normal non-cancerous cell(s), or (3) polypeptides whose expression is specifically limited to only a single (or very limited number of different) tissue type(s) in both the cancerous and non-cancerous state (e.g., normal prostate and prostate tumor tissue). Such polypeptides may remain intracellularly located or may be secreted by the cancer cell. Moreover, such polypeptides may be expressed not by the cancer cell itself, but rather by cells which produce and/or secrete polypeptides having a potentiating or growth-enhancing effect on cancer cells. Such secreted polypeptides are often proteins that provide cancer cells with a growth advantage over normal cells and include such things as, for example, angiogenic factors, cellular adhesion factors, growth factors, and the like. Identification of antagonists of such non-membrane associated polypeptides would be expected to serve as effective therapeutic agents for the treatment of such cancers. Furthermore, identification of the expression pattern of such polypeptides would be useful for the diagnosis of particular cancers in mammals.
Despite the above identified advances in mammalian cancer therapy, there is a great need for additional therapeutic agents capable of detecting the presence of tumor in a mammal and for effectively inhibiting neoplastic cell growth, respectively. Accordingly, it is an objective of the present invention to identify polypeptides, cell membrane-associated, secreted or intracellular polypeptides whose expression is specifically limited to only a single (or very limited number of different) tissue type(s), hematopoietic tissues, in both a cancerous and non-cancerous state, and to use those polypeptides, and their encoding nucleic acids, to produce compositions of matter useful in the therapeutic treatment and/or detection of hematopoietic cancer in mammals.
CD79 is the signaling component of the B-cell receptor consisting of a covalent heterodimer containing CD79a (Igα, mb-1) and CD79b (Igβ, B29). CD79a and CD79b each contain an extracellular immunoglobulin (Ig) domain, a transmembrane domain, and an intracellular signaling domain, an immunoreceptor tyrosine-based activation motif (ITAM) domain. CD79 is expressed on B cells and in Non-Hodgkin's Lymphoma cells (NHLs) (Cabezudo et al., Haematologica, 84:413-418 (1999); D'rena et al., Am. J. Hematol., 64: 275-281 (2000); Olejniczak et al., Immunol. Invest., 35: 93-114 (2006)). CD79a and CD79b and sIg are all required for surface expression of the CD79 (Matsuuchi et al., Curr. Opin. Immunol., 13(3): 270-7)). The average surface expression of CD79b on NHLs is similar to that on normal B-cells, but with a greater range (Matsuuchi et al., Curr. Opin. Immunol., 13(3): 270-7 (2001)).
Given the expression of CD79b, it is beneficial to produce therapeutic antibodies to the CD79b antigen that create minimal or no antigenicity when administered to patients, especially for chronic treatment. The present invention satisfies this and other needs. The present invention provides anti-CD79b antibodies that overcome the limitations of current therapeutic compositions as well as offer additional advantages that will be apparent from the detailed description below.
The use of antibody-drug conjugates (ADC), i e immunoconjugates, for the local delivery of cytotoxic or cytostatic agents, i.e. drugs to kill or inhibit tumor cells in the treatment of cancer (Lambert, J. (2005) Curr. Opinion in Pharmacology 5:543-549; Wu et al (2005) Nature Biotechnology 23(9):1137-1146; Payne, G. (2003) Cancer Cell 3:207-212; Syrigos and Epenetos (1999) Anticancer Research 19:605-614; Niculescu-Duvaz and Springer (1997) Adv. Drug Del. Rev. 26:151-172; U.S. Pat. No. 4,975,278) allows targeted delivery of the drug moiety to tumors, and intracellular accumulation therein, where systemic administration of these unconjugated drug agents may result in unacceptable levels of toxicity to normal cells as well as the tumor cells sought to be eliminated (Baldwin et al (1986) Lancet pp. (Mar. 15, 1986):603-05; Thorpe, (1985) "Antibody Carriers Of Cytotoxic Agents In Cancer Therapy: A Review," in Monoclonal Antibodies '84: Biological And Clinical Applications, A. Pinchera et al (ed.$), pp. 475-506). Efforts to improve the therapeutic index, i.e. maximal efficacy and minimal toxicity of ADC have focused on the selectivity of polyclonal (Rowland et al (1986) Cancer Immunol. Immunother., 21:183-87) and monoclonal antibodies (mAbs) as well as drug-linking and drug-releasing properties (Lambert, J. (2005) Curr. Opinion in Pharmacology 5:543-549). Drug moieties used in antibody drug conjugates include bacterial protein toxins such as diphtheria toxin, plant protein toxins such as ricin, small molecules such as auristatins, geldanamycin (Mandler et al (2000) J. of the Nat. Cancer Inst. 92(19):1573-1581; Mandler et al (2000) Bioorganic & Med. Chem. Letters 10:1025-1028; Mandler et al (2002) Bioconjugate Chem. 13:786-791), maytansinoids (EP 1391213; Liu et al (1996) Proc. Natl. Acad. Sci. USA 93:8618-8623), calicheamicin (Lode et al (1998) Cancer Res. 58:2928; Hinman et al (1993) Cancer Res. 53:3336-3342), daunomycin, doxorubicin, methotrexate, and vindesine (Rowland et al (1986) supra). The drug moieties may affect cytotoxic and cytostatic mechanisms including tubulin binding, DNA binding, or topoisomerase inhibition. Some cytotoxic drugs tend to be inactive or less active when conjugated to large antibodies or protein receptor ligands.
The auristatin peptides, auristatin E (AE) and monomethylauristatin (MMAE), synthetic analogs of dolastatin (WO 02/088172), have been conjugated as drug moieties to: (i) chimeric monoclonal antibodies cBR96 (specific to Lewis Y on carcinomas); (ii) cAC10 which is specific to CD30 on hematological malignancies (Klussman, et al (2004), Bioconjugate Chemistry 15(4):765-773; Doronina et al (2003) Nature Biotechnology 21(7):778-784; Francisco et al (2003) Blood 102(4):1458-1465; US 2004/0018194; (iii) anti-CD20 antibodies such as rituxan (WO 04/032828) for the treatment of CD20-expressing cancers and immune disorders; (iv) anti-EphB2R antibody 2H9 for treatment of colorectal cancer (Mao et al (2004) Cancer Research 64(3):781-788); (v) E-selectin antibody (Bhaskar et al (2003) Cancer Res. 63:6387-6394); (vi) trastuzumab (HERCEPTIN®, US 2005/0238649), and (vi) anti-CD30 antibodies (WO 03/043583). Variants of auristatin E are disclosed in U.S. Pat. Nos. 5,767,237 and 6,124,431. Monomethyl auristatin E conjugated to monoclonal antibodies are disclosed in Senter et al, Proceedings of the American Association for Cancer Research, Volume 45, Abstract Number 623, presented Mar. 28, 2004. Auristatin analogs MMAE and MMAF have been conjugated to various antibodies (US 2005/0238649).
Conventional means of attaching, i.e. linking through covalent bonds, a drug moiety to an antibody generally leads to a heterogeneous mixture of molecules where the drug moieties are attached at a number of sites on the antibody. For example, cytotoxic drugs have typically been conjugated to antibodies through the often-numerous lysine residues of an antibody, generating a heterogeneous antibody-drug conjugate mixture. Depending on reaction conditions, the heterogeneous mixture typically contains a distribution of antibodies with from 0 to about 8, or more, attached drug moieties. In addition, within each subgroup of conjugates with a particular integer ratio of drug moieties to antibody, is a potentially heterogeneous mixture where the drug moiety is attached at various sites on the antibody. Analytical and preparative methods may be inadequate to separate and characterize the antibody-drug conjugate species molecules within the heterogeneous mixture resulting from a conjugation reaction. Antibodies are large, complex and structurally diverse biomolecules, often with many reactive functional groups. Their reactivities with linker reagents and drug-linker intermediates are dependent on factors such as pH, concentration, salt concentration, and co-solvents. Furthermore, the multistep conjugation process may be nonreproducible due to difficulties in controlling the reaction conditions and characterizing reactants and intermediates.
Cysteine thiols are reactive at neutral pH, unlike most amines which are protonated and less nucleophilic near pH 7. Since free thiol (RSH, sulfhydryl) groups are relatively reactive, proteins with cysteine residues often exist in their oxidized form as disulfide-linked oligomers or have internally bridged disulfide groups. Extracellular proteins generally do not have free thiols (Garman, 1997, Non-Radioactive Labelling: A Practical Approach, Academic Press, London, at page 55). Antibody cysteine thiol groups are generally more reactive, i.e. more nucleophilic, towards electrophilic conjugation reagents than antibody amine or hydroxyl groups. Cysteine residues have been introduced into proteins by genetic engineering techniques to form covalent attachments to ligands or to form new intramolecular disulfide bonds (Better et al (1994) J. Biol. Chem. 13:9644-9650; Bernhard et al (1994) Bioconjugate Chem. 5:126-132; Greenwood et al (1994) Therapeutic Immunology 1:247-255; Tu et al (1999) Proc. Natl. Acad. Sci USA 96:4862-4867; Kanno et al (2000) J. of Biotechnology, 76:207-214; Chmura et al (2001) Proc. Nat. Acad. Sci. USA 98(15):8480-8484; U.S. Pat. No. 6,248,564). However, engineering in cysteine thiol groups by the mutation of various amino acid residues of a protein to cysteine amino acids is potentially problematic, particularly in the case of unpaired (free Cys) residues or those which are relatively accessible for reaction or oxidation. In concentrated solutions of the protein, whether in the periplasm of E. coli, culture supernatants, or partially or completely purified protein, unpaired Cys residues on the surface of the protein can pair and oxidize to form intermolecular disulfides, and hence protein dimers or multimers. Disulfide dimer formation renders the new Cys unreactive for conjugation to a drug, ligand, or other label. Furthermore, if the protein oxidatively forms an intramolecular disulfide bond between the newly engineered Cys and an existing Cys residue, both Cys thiol groups are unavailable for active site participation and interactions. Furthermore, the protein may be rendered inactive or non-specific, by misfolding or loss of tertiary structure (Zhang et al (2002) Anal. Biochem. 311:1-9).
Cysteine-engineered antibodies have been designed as FAB antibody fragments (thioFab) and expressed as full-length, IgG monoclonal (thioMab) antibodies (Junutula, J. R. et al. (2008) J Immunol Methods 332:41-52; US 2007/0092940, the contents of which are incorporated by reference). ThioFab and ThioMab antibodies have been conjugated through linkers at the newly introduced cysteine thiols with thiol-reactive linker reagents and drug-linker reagents to prepare antibody drug conjugates (Thio ADC).
All references cited herein, including patent applications and publications, are incorporated by reference in their entirety.

Humanized anti-CD79b antibodies and immunoconjugates and methods of use