A system, apparatus and method are provided for intermittent location reporting. The apparatus includes a global positioning system (GPS) receiver, a transceiver, and a controller. The transceiver is a WiFi or WiMAX transceiver. The controller reads a current geographical location of the apparatus and determines whether communication with a location monitoring application (LMA) is possible. If communication with the LMA is not possible, the controller stores the current geographical location. When communication with the LMA is again possible, the controller sends any stored geographical locations. The controller may store timestamps associated with the geographical locations. The controller may send the geographical locations to the LMA at intervals determined by predefined rules.

Processing facilities are often managed using process control systems. Example processing facilities include manufacturing plants, chemical plants, crude oil refineries, ore processing plants, and coal or other types of mines. A company or other business entity may have several, geographically separated processing facilities between which assets are moved.
Asset tracking systems may be used to track the locations of assets within a processing facility. These systems are routinely used as part of process control systems or security systems, allowing the systems to identify when assets enter predefined areas or when assets are moved to or from their designated locations.

Method and apparatus for intermittent location reporting


A locking device for a motor vehicle comprising an actuator, a lock with a locking mechanism, comprising a rotary latch and at least one pawl, the actuator and the lock can be interconnected by a Bowden cable and the Bowden cable has provision for actively blocking a force transmitted by the Bowden cable.

A lock for a motor vehicle, also known as a locking system, is largely installed onto the locking mechanisms which consist of a catch and at least one pawl. The locking mechanism in the lock interacts with a lock holder which is either attached to the chassis of the motor vehicle or the door, flap, sliding door, etc. The relative movement between the lock holder and the catch causes the catch to be pivoted and simultaneously the pawl engages with the catch.


The present invention discloses isolates and fractions from a phyto-percolate and methods for affecting various cytokines by administering an effective amount of one or more of said isolates or fractions to an animal. In various exemplary embodiments, the isolates are useful for the treatment of bovine, canine and swine infection or inflammation, including bovine mastitis, by regulation of TNF-α, lactoferrin, IFN-γ, IL-1β, serum amyloid-A (SAA), IL-6 and/or β-defensin associated with infection or an immune response generally.

Cytokines are a broad class of proteins that are secreted by various cell types, including cells of the immune system. One function of cytokines is to carry various signals between cells and thus control activity among cells. Several factors can cause cells to secrete cytokines, including a cell's encounter with pathogens that may cause disease. In certain instances, cells will secrete cytokines as a means of organizing a natural defense against the pathogen or disease.
There are numerous cytokines, such as interleukins ("IL") produced by white blood cells. Individual interleukins include, for example, IL-2, IL-10, and IL-17A. Each of these interleukins have specific functions and effects, such as decreasing or increasing inflammation, stimulating the proliferation and function of various cell types, and regulating the production of antibodies. For example, IL-2 contributes toward inflammation and may be considered as inflammatory proteins, while IL-10 may be considered an anti-inflammatory protein that decreases inflammation. Therefore, the more IL-2 produced, the greater the inflammation and the more IL-10 produced the lesser the inflammation.
Interleukins have been determined to be involved in many processes, including, but not limited to, inflammation. For example, there is substantial evidence suggesting that IL-2 suppresses the production of immunoglobulins. In contrast, there is substantial evidence suggesting that IL-10 enhances immunoglobulin production.
Another cytokine is interferon-gamma or IFN-γ. IFN-γ is critical for innate and adaptive immunity against viral and intracellular bacterial defense functions and for tumor control. IFN-γ has been shown to alter the transcription of over thirty genes and to produce such affects as increasing T-helper (Th2) cell activity, promoting natural killer (NK) cell activity, and affecting various other molecular signaling pathways.
Other cytokines include tumor necrosis factor (TNF) alpha, or TNF-α, which is involved in the regulation of immune cells. Further, elevated production of TNF-α has been implicated as a contributing factor in a variety of human diseases, including cancer. TNF-α contributes to inflammation and may be considered an inflammatory protein. The more TNF-α produced, the greater the inflammation.
Yet another cytokine is granulocyte-macrophage colony-stimulating factor or GM-CSF. GM-CSF is a white blood cell growth factor that is known to stimulate stem cells, and is part of the immune/inflammatory cascade.
A transcription factor known as "nuclear factor kappa beta" or NF-κB is an intracellular protein that functions as a regulator of gene transcription and plays an important role in various biological processes and pathology. NF-κB has been found to play an important role in regulating the immune system in response to infection, and in several inflammatory pathways including the production of cyclooxygenase, nitric oxide synthase and other pro-inflammatory proteins. Inappropriate regulation of NF-κB has been linked to cancer, inflammatory and autoimmune diseases, septic shock, viral infection, and improper immune development and certain studies have linked NF-κB to processes involving synaptic plasticity and memory. The role of NF-κB and various cytokines is discussed in the article entitled Using Chemopreventive Agents to Enhance the Efficacy of Cancer Therapy, by Sarkar, et al., and published by the American Association for Cancer Research on Apr. 1, 2006, which is herein incorporated by reference in its entirety. Further, various viruses, including the HIV virus have molecular binding sites for NF-κB, thus indicating the NF-κB may be a critical component for activating the HIV virus from a latent state to an active state.
Therefore, the regulation of cytokines and/or transcription factors such as NF-κB can be a critical process in providing treatment for various ailments. For example, since IL-10 has anti-inflammatory properties, increasing IL-10 in a patient suffering from a chronic inflammatory condition can be used to treat the inflammation. Alternatively, since NF-κB is a factor for activating the HIV virus from a latent state to an active state, reducing the amount of NF-κB could delay or prevent the HIV virus from being activated.
Although there are known compositions and methods for regulating cytokines and NF-κB, many of these known compositions and methods are irritating to cells or have a toxic effect on cells. Further, many known compositions and methods for regulating cytokines and NF-κB regulate many cytokines in the same manner, some of which may hinder the overall desired effect of the treatment. For example, there are known compositions and methods for treating inflammation that up-regulate anti-inflammatory cytokines such as IL-10, but these compositions also result in up-regulation of IL-2, an inflammatory cytokine that reduces the effect of the IL-10.
Therefore, it would be advantageous to provide improved compounds, compositions and methods of regulating anti-inflammatory cytokines and transcription factors such as NF-κB on a cellular level. Moreover, providing compounds, compositions and methods that could regulate selected cytokines and transcription factors NF-κB to achieve a multitude of effects for the treatment of various health problems would be desirable. One example of such specific regulation of multiple cytokines would be selected compounds or a composition that up-regulates IL-10 without up-regulating IL-2, or even while down-regulating IL-2, thus increasing anti-inflammatory cytokines while reducing or maintaining the level of pro-inflammatory cytokines in order to reduce inflammation. It would also be desirable to provide selected compounds, compositions, and methods to affect various cytokines and transcription factors such as NF-κB that are not irritants, are non-toxic, easy to manufacture and distribute, and not expensive to produce, isolate and purify.

This patent is subject to a terminal disclaimer.

Compounds and methods for affecting cytokines


A delay circuit includes a delay unit configured to generate a delayed transmission signal by delaying a transmission signal activated when a first signal or a second signal is activated, a signal type storing unit configured to store whether the first signal and the second signal is activated, and a transmitting unit configured to transmits the delayed transmission signal as a first delayed signal or a second delayed signal in response to a value stored in the signal type storing unit.

1. Field
Exemplary embodiments of the present invention relate to a delay circuit and a signal delay method.
2. Description of the Related Art
In the field of integrated circuit, various circuits included in integrated circuits do not operate alone, but operate while exchanging signals (for example, data) with other circuits. In general in order that a circuit A and a circuit B interact with each other, the circuit A requests the circuit B to do an operation, and a predetermined standby time is required until the circuit B operates in response to the request. The standby time is called latency. The reason that the standby time is required is for increase transmission efficiency of signal between the circuit A and the circuit B and ensuring the time for the internal operation of the circuit B.
A memory controller and a memory may be considered as an example of interaction between two or more circuits included in an integrated circuit system. When the memory controller applies a write command to the memory, the memory stores the data input from the memory controller in a memory cell. However, the memory cannot receive the data from the memory controller, upon receiving the write command. This is because the memory needs time to internally prepare for storing the data. The factor defined for the preparation is write latency.
In general, an address for designating the memory cell to store data in is also applied with the write command. However, the data to be stored is input to the memory after the write latency passes from when the write command is applied, so that it is necessary to delay the address for the write latency.
Meanwhile, over DDR2 and DDR3 SDRAM, a new concept, an AL (Additive Latency) has been introduced to increase efficiency of a data bus. Therefore, even if read/write commands or an address is applied from the outside before tRCD (RAS to CAS delay), it is delayed as much as the additive latency, internal read/write commands or an internal address is generated after the tRCD, and a read/write operation of a semiconductor memory device is performed. The additive latency is set by an EMRS, and the additive latency (AL) is fixed at a specific value in the DDR2 SDRAM, but the additive latency (AL) is 0, CL-1, and CL-2, interlocked with the CAS latency (CL). The additive latencies are applied to both read/write commands, and accordingly the address should be delayed as much as the additive latency.
Hereinafter, a delay circuit of a memory which delays a read command or a write command will be described.
FIG. 1 is a diagram illustrating the configuration of a conventional delay circuit.
As illustrated in FIG. 1, the conventional delay circuit includes a first delay unit 110 configured to generate a delayed read command RD_DEL by delaying a read command RD and a second delay unit 120 configured to generate a delayed write command WT_DEL by delaying a write command WT. The delay circuit generates a delayed read command RD_DEL or a delayed write command WT_DEL by delaying a read command RD or a write command WT. It is described when the delay circuit of FIG. 1 generates a delayed read command RD_DEL and a delayed write command WT_DEL by delaying a read command RD and a write command WT within the range of 1 to 7 clock cycles. The range of delay values where the delay circuit can delay the command RD and WT may depend on the design. The delay value of the delay circuit delaying the commands RD and WT may be an additive latency.
Hereinafter, the delay circuit will be described with reference to FIG. 1.
The first delay unit 110 includes a plurality of first shifting units D11 to D18 and a plurality of first selection units S11 to S13, which are connected in series, respectively. The shifting unit. D11 in the first shifting units D11 to D18 outputs an applied read command RD in synchronization with a clock CLK. The shifting units D12 to D18 outputs signals input to them by delaying the signals by one clock cycle in synchronization with the clock CLK. The first shifting units may be D-flip flops.
The first selection units S11 to S13 selects a first shifting unit through which the applied read command RD passes, in the first shifting units D11 to D18 in response to delay information DEL<0:3>. For example, the delay value of the first delay unit 110 is selected as one clock cycle, the selection units S11 to S13 do not pass the applied read command RD through all the shifting units D12 to D17 in response to delay information (DEL<0:3>). Therefore, the read command RD is delayed by one clock cycle by the shifting unit D18 and transmitted as a delayed read command RD_DEL (all the selection units S11, S12 and S13 select and output the signal input to the terminal 0). For example, the delay value of the first delay unit 110 is selected as five clock cycles, the selection units S11 to S13 pass the applied read command RD through all the shifting units D12 to D15 in response to delay information (DEL<0:3>). The output of the shifting unit D15 is transmitted as a delayed read command RD_DEL through the shifting unit D18 (the selection units S11 and S12 select and output the signal input to the terminal 1 and the selection unit S13 selects and outputs the signal input to the terminal 0). For example, the delay value of the first delay unit 110 is selected as six clock cycles, the selection units S11 to S13 pass the applied read command RD through all the shifting units D12 to D16 in response to delay information (DEL<0:3>). The output of the shifting unit D16 is transmitted as a delayed read command RD_DEL through the shifting unit D18 (all the selection units S11, S12, and S13 select and output the signal input to the terminal 1).
The second delay unit 120 includes a plurality of second shifting units D21 to D28 and a plurality of second selection units S21 to S23, which are connected in series, respectively. The second delay unit 120 has the same configuration and operation as those of the first delay unit 110, except that they generate a delayed write command WT_DEL by delaying a write command WT.
In the delay circuits of the related art, the first delay unit 110 and the second delay unit 120 both include the shifting units D11 to D18 and D21 to D28, respectively, for delaying applied commands RD and WT by one clock cycle. In general, the shifting unit includes a D-flip flop and the D-flip flop occupies a large area and consumes a large amount of current. Therefore, as the first delay unit 110 and the second delay unit 120 each include a plurality of D-flip flops, the area and the consumed current of the delay circuit are large.

Delay circuit and delay method using the same


A wireless signal access apparatus receives wireless signals of IEEE 802.11 standard for controlling at least one appliance. The appliance may receive control signals of IEEE 802.15 standard, to be controlled according to the control signals. The wireless signal access apparatus receives the wireless signals having control data to generate the control signal of IEEE 802.15 standard, and send it to the appliance for omnidirectional remote control of the appliance.

1. Field of the Invention
The present invention relates generally to a remote control technology, and more particularly, to a wireless signal access apparatus to remotely control an appliance, and a method for remotely controlling the appliance through the apparatus.
2. Description of the Related Art
With advancement in science and technology today, more and more appliances at home or at office are operated by remote controllers. However, the conventional remote controllers emit infrared rays to remotely control the appliances, so they need to be aimed right at the appliances at operation. Otherwise, there are always many remote controllers at home for various appliances, which is quite inconvenient for management.

Wireless signal access apparatus and method for remotely controlling  appliance through the same


An endoscopic surgical instrument suitable for use with a needle-grasper having a rotational translation device for creating rotational motion at the distal end of the surgical instrument in a non 1:1 ratio to rotational energy imparted at the handle of the surgical instrument. The shaft of the surgical instrument has an articulated segment capable of remote adjustment to articulate the effector unit at the end of the surgical instrument. The effector unit may be a needle-gripper having an upwardly pointed V-shaped notch in a channeled upper jaw, a convex gripping surface on the lower jaw, such that grasping a curved suture needle between the upper and lower jaw serves to automatically orient the needle perpendicular to the needle-gripper with the curvature pointed down. Conically tapered edges on the upper jaw further facilitate this orientation. A reciprocal motion transmission occurs between the handle and the effector unit so that gripping the levers on the handle serves to operate a function in the effector unit. The device is suitable for manual operation by a surgeon performing endoscopic surgical manipulations directly and without the intervention of motors or the like.

1. Field of the Invention
This invention relates to a surgical instrument for remote manipulation and more particularly to an instrument for use in endoscopic surgery, the instrument having an articulated shaft and transmitting rotational motion to the distal end of the instrument.
Minimally invasive surgery (MIS) such as laparoscopic, endoscopic, hysteroscopic, and arthroscopic surgery (referred to hereafter generally as endoscopic surgery), is becoming more widely used because it is less traumatic to the patient, generally involves less hospitalization time, less discomfort and less risk to the patient, and is usually less costly than traditional open surgery.
Such a procedure is typically performed by making a small incision in the patient which provides access to the area to be treated. A trocar sheath may be inserted in the incision and an airtight seal around the trocar established. The area under the skin which is to be treated may be dissected from surrounding tissue by, for example, balloon dissection. With or without dissection, the area may be expanded slightly as by insufflation with CO.sub.2 in order to create a cavity within which to perform the surgical procedure. Access to this cavity may be through by one or more trocar sleeves which may be configured to permit the slidable insertion of endoscopes and surgical instruments without compromising the air tight seal around the trocar sheath. Each such endoscopic surgical instrument is often inserted through a different incision.
The endoscopic surgery is generally preformed using elongate instruments slidably inserted through the trocar sleeves, or if the endoscopic surgery is performed in a naturally occurring body cavity, such as the uterus, the instruments may be inserted through a relatively narrow body orifice such as the cervix. The manipulations being performed by the instruments during endoscopic surgery are generally observed through an endoscope which may be inserted through a separate trocar into the operating cavity. Alternatively, the endoscope may be contained within a surgical tube which also contains surgical instruments. In any event, the operator must perform the surgical manipulations using an effector unit, such as a scalpel or needle gripper on the end of the surgical instrument remotely located from the operator's hands and confined within a relatively small cavity created for the operation. The manipulation must be performed while observing the procedure with an endoscope. The image from the endoscope is often displayed on a video screen and generally results in an image having little or no depth perception.
Of particular interest is suturing or tying knots during endoscopic surgery. Suturing and tying knots using remote effector units while observing the manipulation through an endoscope is very challenging for the surgeon. Traditionally the surgical instruments employed to perform endoscopic suturing may include simple endoscopic needle holders, a variety of specialized needle drivers, and motorized telesurgical systems. The problems associated with remote knot tying have lead to the development of such instruments and devices as pre-tied knots, ultrasonic welded knots, beads swaged in such a way as to facilitate the crimping of sutures together, and, again, motorized systems. Most of the methods described above are limited in use to interrupted rather than continuous suturing. Some, for example the telesurgical system, require complex instrumentation and may not be available for all endoscopic procedures, especially the simpler procedures. In addition, the motorized systems generally limit or eliminate the kinesthetic ability of the surgeon to sense and directly manipulate the suture or needle.
One particularly cumbersome technique that is often used to achieve suturing using traditional endoscopic instruments, is the "hand off" of the needle from one instrument to another. This technique exacerbates the difficulty of remote manipulation in limited space and restricted visualization with the requirement of coordination of two or more instruments. This technique involves insertion of the suturing needle by the operative instrument into the tissue to be sewn. The needle is then pushed forward, driving the needle through the tissue. A second instrument, may apply counter-pressure to the tissue at the location where the sharp tip of the needle will emerge at the end of the stitch. This entrance drive of the needle through the tissue generally involves a rotating motion, particularly critical where a sharply curved needle is used.
Once the tip of the needle emerges from the tissue, it is extracted by the assisting instrument grasping the tip of the needle and pulling. The principal needle driver releases its grip on the needle and may be placed beside the location where the needle is exiting the tissue to act as a counter-pressure instrument in place of the assisting instrument which is now pulling the needle from the tissue, pushing the tissue down while the needle is being pulled out by the assisting instrument. As with the entrance drive, the extracting motion often involves significant rotation in order to avoid tearing the tissue, particularly with a sharply curved needle.
After the needle is extracted, the trailing suture may be pulled through the tissue, again with the use of two cooperating instruments, each pulling at the suture sequentially until the correct amount of suture has been pulled through the tissue.
For single stitch technique, the suture is then tied, itself a complex procedure especially where performed with a viewing system having very limited depth perception. When continuous sewing is performed, the needle is grasped by the principal operative instrument after the suture is pulled through the tissue as desired in preparation to performing the sequence again to form a second stitch. First, the assisting instrument grasps the fully extracted needle and holds it in an optimal position for the principal needle driver to grasp. The assisting second instrument generally must grasp the needle near the tip so that the principal needle driver can grasp the needle far enough to the rear of the sharp tip to provide adequate length to pass the needle through the tissue layers during the next entrance drive so that enough of the needle tip will exit to be grasped by the assisting instrument. The assisting instrument must hold the needle at an appropriate orientation so that the principal needle driver will grasp the needle at the proper orientation for making the next entry into the tissue. Since traditional endoscopic instruments have a limited range of rotation at the distal end relative to the handle, this orientation is critical. Once again, this needle insertion and drive through the tissue, and subsequent extraction of the needle at the end of the stitch, requires significant rotational motion. It is often desirable during such procedures to hold the forearms of the operator relatively stationary, the rotational motion imparted by the hands of the operator rotating at the wrists may be insufficient to successfully accomplish the stitching.
The efforts required for a successful hand-off and continuous suturing highlights a number of problems with current endoscopic tools. It is a problem to properly orient the needle relative to the needle gripper. For effective suturing, the curved needle should be grasped by the principal needle driver with the needle extending perpendicular to the grasper and with a sufficient length of the front end of the needle protruding so that the needle may be inserted into the tissue. This is very difficult when the operator is viewing the procedure with limited or no depth perception.
It is also a problem to provide sufficient rotation after grasping the needle to rotate the needle to insert the tip into the desired location to start the stitch. This is particularly problematic given the limited rotational motion of the human wrist, or with mechanical devices such as side mounted rotational knobs that are sometimes provided to achieve rotation at the distal end at an endoscopic tool. The requirement for two instruments to carry out this technique may also create the need for additional incisions, further complicating the procedure and adding additional trauma, risk and expense to the procedure.
Another problem presented by the use of some current endoscopic instruments with needle grabbers is access to a location that is at an angle to the end of a straight surgical instrument. An endoscopic surgical instrument must generally be straight to be inserted through a trocar sleeve. Although some angle of reach is available by twisting the trocar in the patient's body and thereby pointing the instrument in slightly different directions, this is obviously limited by such considerations as the need to keep the trocar incision relatively airtight if the operating cavity is insufflated, and the need to avoid traumatizing the patient unnecessarily. Since movement of the instrument and the twisting and straining of the trocar at the site of the incision can threaten the airtight seal and be traumatic to the patient, it would be preferable to reach locations within the operating area by articulating the end portion of the surgical instrument without having to twist the instrument or the trocar at the site of the incision. Some form of articulation within the instrument shaft, preferably near the distal end of the instrument shaft, with the articulation being controllably adjustable by the operator after insertion of the instrument, is advantageous.
Various endoscopic surgical instruments, such as surgical staplers, and surgical retraction devices for use in endoscopic procedures, are disclosed in the prior art. See, for example, U.S. Pat. No. 5,192,288, directed to a surgical clip applier and U.S. Pat. No. 5,431,669, directed to a surgical clip applier with distal hook. Also disclosed in the art are endoscopic surgical instruments having knobs for the adjustment of angles of articulation and rotation of a staple applier as disclosed in U.S. Pat. No. 5,662,662, directed to a surgical instrument and method, and U.S. Pat. No. 5,607,095, directed to an endoscopic surgical instrument with pivotable and rotatable staple cartridge.
Graspers for suture needles are also shown in the prior art. For example, U.S. Pat. No. 5,015,250, directed to a medical instrument for driving a suture needle, discloses a needle driver instrument suitable for use with a trocar sheath in operative endoscopic surgical procedures for holding and driving a curved suture needle.
Given the needs of those operating in the environment of endoscopic surgery, it would be desirable to provide a surgical instrument directly responsive to hand and forearm rotation which is capable of imparting rotational motion in a non 1:1 ratio to an effector unit such as a needle gripper. It would also be desirable to provide a needle gripper which would automatically orient a curved suture needle. Additionally, it would be desirable to provide a needle gripper which could be remotely operated by, for example, operating a reciprocating rod at the handle of a surgical instrument to open and close the jaws of a needle gripper at the distal end of an elongate shaft on the surgical instrument. Moreover, it would also be desirable to provide a surgical instrument such as a needle gripper that could simultaneously be manipulated in multiple ways, such as opening and closing and simultaneously rotating, by the same hand of the operator, thus providing dynamic control over the manipulation of effector unit such as a needle gripper.

Endoscopic surgical instrument for rotational manipulation


A circuit in a transmitter with multiple power amplifiers includes multiple individual linearizer circuits each receiving a corresponding input signal and each providing a conditioned input signal to a corresponding power amplifier. The linearizer circuit each include: (a) a pre-distortion circuit receiving (i) the corresponding input signal and (ii) the output signal of a corresponding power amplifier, and providing a pre-distortion signal; (b) a cancelation circuit receiving an interfering signal and providing a cancelation signal; and (c) a combination circuit that combines the cancelation signal and the pre-distortion signal to provide a conditioned input signal to the corresponding power amplifier.

1. Field of the Invention
The present invention relates to linearization of power amplifiers. In particular, the present invention relates to linearization of power amplifiers in a multi-path transmitter.
2. Discussion of the Related Art
To facilitate deployment and to reduce operating expense, small cells in a cellular communication system must be highly efficient (e.g., have a small form factor and be low-power). With high efficiency, the size, the weight and the cost of components, heat sinks, power supplies and enclosures can be reduced. For indoor use, Power over Ethernet (PoE) is another highly desirable technology that minimizes installation cost. Recent advances in adaptive, closed-loop RF linearization have made it possible to economically linearize RF power amplifiers, including power amplifiers that are Class A, Class AB or Doherty, even at the low power levels used in small cells. To linearize a power amplifier, a linearization circuit conditions the input signal by combining it with a pre-distortion signal, such that the output of the power amplifier bears a substantially linear relationship to the input signal.


According to an example aspect of the present invention, there is provided a process for the conversion of cellulosic waste material into a recycled cellulose product comprising the steps of cooking the waste material in a cooking liquor to remove lignin from the waste material and provide a delignified pulp, dissolving the delignified pulp in an ionic liquid to provide a spinning dope suitable for dry jet-wet spinning in an ionic liquid solution, and subjecting the spinning dope to a further processing step to provide a recycled cellulose product, said further step selected from the group of spinning cellulose fibers for use in textiles from the solution, extruding a film product for use in packaging, regenerating the dope as a hydrogel and regenerating the dope as an aerogel.

The recycling rate of newspapers prepared from mechanical pulps (TMP, CTMP) has been reported to be 73% (Holik, 2006) in the CEPI countries. This figure shows that the recycling of newspaper is quite efficient, but the added value is still low. Also in the view of a declining newspaper market, alternative uses with a higher valorisation potential should be envisioned. The conversion into e.g. man-made cellulose fibers would result in an almost thirtyfold increase of the raw material value (100 € to 3000 €/t).
The use of waste paper for the production of regenerated cellulose fibers based on Lyocell spinning technology is known. For example, Firgo et al reported about the use of deinked waste paper in the NMMO process. However, even though the waste paper was from wood-free paper (lignin-free) the tenacity did not exceed 20 cN/tex which is hardly acceptable in the market (Firgo et al., 1996). Quite recently, the production of regenerated cellulose fibers made from pretreated fine paper with a lignin content of only 1.1% using the Ioncell-F process was reported (Ma et al., 2016). The mechanical properties of the produced fibers were 44.1 and 32.0 cN/tex in the conditioned and wet states, respectively, and thus meet the requirements of modern textile fibers.
Under aqueous alkaline conditions the cellulose DP is largely preserved provided that the temperature remains below 140° C. to avoid alkaline hydrolysis of cellulose (Nieminen et al., 2014). However, without any efficient nucleophile such as hydrogensulfide or sulfite anions an efficient delignification is not possible at low temperatures. Replacing water by an organic solvent for lignin promotes delignification and would allow the use of a higher temperature to enhance the efficiency of delignification while cellulose depolymerization can be kept at a moderate level. Demirbas and Celik proposed alkaline glycerol as an efficient delignification system. However, very high temperatures (>210° C.) and moderate delignification efficiencies were reported (Demirbas, 1998; Demirbas & Celik, 2005). Quite recently Hundt et al. demonstrated that the use of (almost) water-free glycerol in combination with potassium hydroxide in very high concentrations could remove the lignin from pine wood to very low levels (kappa numbers below 10) while cellulose remained largely preserved (Hundt et al., 2014; Hundt et al., 2013a; Hundt et al., 2013b). The obtained pulps were characterized only regarding their residual lignin content and their crystallinity index because the target was to convert the polysaccharides into monosugars by enzymatic treatment for subsequent fermentation. The cellulose DP or even the molecular weight distribution of the pulps were not determined.
This fractionation method seems to be attractive because glycerol is a cheap and green waste product of biodiesel production. One of the drawbacks for the commercialization of the process is the substantial amount of KOH charged to the solvent. An integrated lignocellulose biorefinery concept based on a continuous pulping process was recently published (Hundt et al., 2016) where the authors suggest the use of electrodialysis with bipolar membranes for the recycling of potassium hydroxide. The excess water in the glycerol (from washing) is removed by evaporation in a thin film evaporator. Still, a substantial improvement of the process conditions, thereby focusing on the reduction of the alkali charge and the replacement of KOH by NaOH, will be necessary to render the alkaline glycerol fractionation a commercially feasible process.

Method to convert mechanical pulp derived waste material into value added cellulose products


There is described a fixing bath for developed silver halide photographic material which comprises as the active silver halide solvent a combination of sodium thiosulphate and potassium thiosulphate, the molar ratio of sodium to potassium being from about 2:3 to about 3:2.

After silver halide material has been exposed and developed, it is necessary to remove the unexposed and hence undeveloped silver halide remaining in the material to render the material light stable. The most commonly used silver halide solvents used in fixing baths to remove or `fix-out` the undeveloped silver are either an alkali metal thiosulphate or ammonium thiosulphate. The thiosulphate first used was sodium thiosulphate, the hypo of the old photographic books. More recently, ammonium thiosulphate has been used as it removes the undeveloped silver very much faster than sodium thiosulphate. Potassium thiosulphate has also been proposed to be used, but as it is more expensive than sodium thiosulphate and not much if any faster at fixing out, it has not been used much commercially.
Most often the dissolved or fixed out silver is removed from the fixing solution by electrolysis, ion exchange or other means and the used desilvered fixing solution is discharged into the effluent system. However, for environmental reasons, in recent years the control of effluent has become very strict. Sodium or potassium salts which are very wide-spread in nature do not significantly affect the aqueous environment into which the effluent is discharged but ammonium salts tend to act as a fertilizer for the micro-organisms in the aqueous environment and if such micro-organisms proliferate greatly they reduce the oxygen content of the aqueous environment. This is in detriment to the higher species found in such environment such as fish. Further, when such microorganisms die, this further consumes oxygen and renders the water foul and unfit to support fish or higher-plant life. Thus it is desirable to find a fixing solution which contains no ammonium thiosulphate but which fixes out silver faster than sodium thiosulphate. In the past, various other salts have been used as fixing agents such as alkali metal thiocyanates but in general these are even less environmentally friendly than ammonium thiosulphate.


A method for an engine may comprise, responsive to a first condition comprising a reference voltage of a first exhaust oxygen sensor operating in variable voltage mode increasing above a threshold voltage, determining a change in an output of the first exhaust oxygen sensor corresponding to the increase in the reference voltage, correcting the output of the first oxygen sensor based on the output change, and adjusting engine operation based on the corrected output. In this way, the accuracy of air-fuel estimates based on the exhaust gas sensor can be preserved, and closed loop fuel control of the engine can be maintained even when the exhaust oxygen sensor is operating VVS mode, thereby reducing engine emissions, increasing fuel economy, and increasing vehicle drivability.

An exhaust gas sensor (e.g., exhaust oxygen sensor) may be positioned in an exhaust system of a vehicle and operated to provide indications of various exhaust gas constituents. In one example, the exhaust gas sensor may be used to detect an air-fuel ratio of exhaust gas exhausted from an internal combustion engine of the vehicle. The exhaust gas sensor readings may then be used to control operation of the internal combustion engine to propel the vehicle. In another example, outputs of the exhaust gas sensor may be used to estimate a water content in the exhaust gas. Water content estimated using the exhaust gas oxygen sensor may be used to infer an ambient humidity during engine operation. Further still, the water content may be used to infer an alcohol content of a fuel burned in the engine. Under select conditions, the exhaust gas sensor may be operated as a variable voltage (VVs) oxygen sensor in order to more accurately determine exhaust water content. When operating in the VVs mode, a reference voltage of the exhaust gas sensor is increased from a lower, base voltage (e.g., approximately 450 mv) to a higher, target voltage (e.g., in a range of 900-1100 mV). In some examples, the higher, target voltage may be a voltage at which water molecules are partially or fully dissociated at the oxygen sensor while the base voltage is a voltage at which water molecules are not dissociated at the sensor.
However, the inventors herein have recognized potential issues with operating the exhaust gas sensor in the VVs mode. As one example, air-fuel estimates with the exhaust gas sensor may be invalid when the reference voltage is increased above the base voltage since the oxygen sensor is no longer stoichiometric. For example, at higher reference voltages, the sensor dissociates water vapor and carbon dioxide which contribute to the oxygen concentration represented in the pumping current output by the exhaust gas sensor. Since water vapor and carbon dioxide change with ambient humidity and ethanol concentration in the fuel, and these parameters are unknown, traditional pumping current to air-fuel ratio transfer functions are not accurate at elevated reference voltages. As a result, the vehicle may have to operate in open loop fuel control which may negatively impact emissions, fuel economy, and drivability.
In one example, the issues described above may be at least partially addressed by a method for an engine comprising: responsive to a first condition comprising a reference voltage of a first exhaust oxygen sensor operating in variable voltage mode increasing above a threshold voltage, determining a change in an output of the first exhaust oxygen sensor corresponding to the increase in the reference voltage, correcting the output of the first oxygen sensor based on the output change, and adjusting engine operation based on the corrected output.
In another example, a method may comprise, during operation of a combustion engine in a closed loop control mode based on air-fuel ratio, correcting an output of a first exhaust oxygen sensor operating in a variable voltage mode, and determining the air-fuel ratio based on the corrected output of the first exhaust oxygen sensor.
In this way, the technical effect of preserving the accuracy of air-fuel estimates based on the exhaust gas sensor, and maintaining closed loop fuel control of the engine even when the exhaust oxygen sensor is operating VVS mode can be achieved, thereby reducing engine emissions, increasing fuel economy, and increasing vehicle drivability.
It should be understood that the summary above is provided to introduce in simplified form a selection of concepts that are further described in the detailed description. It is not meant to identify key or essential features of the claimed subject matter, the scope of which is defined uniquely by the claims that follow the detailed description. Furthermore, the claimed subject matter is not limited to implementations that solve any disadvantages noted above or in any part of this disclosure.

Methods and systems for estimating an air-fuel ratio with a variable voltage oxygen sensor


The invention relates to certain 6-amino-substituted 2-pyridinesulfonylureas, intermediates thereof, and compositions and methods of their use.

This invention relates to novel pyridine sulfonylurea herbicidal compounds, agriculturally suitable compositions thereof and a method of using them to control the growth of undesired vegetation.
New compounds effective for controlling the growth of undesired vegetation are in constant demand. In the most common situation, such compounds are sought to selectively control the growth of weeds in useful crops such as cotton, rice, corn, wheat and soybeans, to name a few. Unchecked weed growth in such crops can cause significant losses, reducing profit to the farmer and increasing costs to the consumer. In other situations, herbicides are desired which will control all plant growth. Examples of areas in which complete control of all vegetation is desired are areas around railroad tracks and industrial storage areas. There are many products commercially available for these purposes, but the search continues for products which are more effective, less costly and environmentally safe.
The "sulfonylurea" herbicides are an extremely potent class of herbicides discovered within the last few years. A multitude of structural variations exist within this class of herbicides, but they generally consist of a sulfonylurea bridge, --SO.sub.2 NHCONH--, linking two aromatic or heteroaromatic rings.
U.S. Pat. Nos. 4,579,583 and 4,690,707 disclose herbicidal pyridinesulfonylureas of the formula ##STR1## wherein XA is NR.sub.6 R.sub.7; and
R.sub.6 and R.sub.7 are independently H, C.sub.1 -C.sub.4 alkyl, C.sub.3 -C.sub.6 alkenyl, C.sub.3 -C.sub.6 alkynyl, C.sub.3 -C.sub.6 alkoxyalkyl, C.sub.1 -C.sub.4 cyanoalkyl, or taken together form a 5- or 6-membered heterocyclic ring which may also contain O, S, SO or NR.sub.8. PA0 R.sub.2 is H, Cl, Br or CH.sub.3. PA0 R.sub.1 is NH(C.sub.1 C.sub.4)alkyl or N(C.sub.1 -C.sub.4 alkyl).sub.2. PA0 R.sub.1 is NH.sub.2, NH(C.sub.1 -C.sub.4)alkyl or N(C.sub.1 -C.sub.4 alkyl).sub.2. PA0 R is H or CH.sub.3 ; PA0 R.sub.1 is H, F, Cl, Br, I, CN, C.sub.1 -C.sub.2 alkyl, C.sub.1 -C.sub.2 haloalkyl, OCH.sub.3, OCH.sub.2 CH.sub.3, OCH.sub.2 CF.sub.3, OCF.sub.2 H, SCH.sub.3, SCF.sub.2 H, C.sub.1 -C.sub.3 alkylsulfonyl or SO.sub.2 CF.sub.2 H; PA0 R.sub.2 is H, C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.2 haloalkyl, CN, OH, C.sub.1 -C.sub.2 alkoxy, NH.sub.2, NHCH.sub.3, N(CH.sub.3)2, C.sub.1 C.sub.2 alkyl substituted by CN, C.sub.1 -C.sub.2 alkoxy or C.sub.1 -C.sub.2 alkylthio, C.sub.3 -C.sub.4 cycloalkyl, C.sub.3 -C.sub.4 alkenyl, C.sub.3 -C.sub.4 alkynyl or C(O)R.sub.5 ; PA0 R.sub.3 is H, C.sub.1 C.sub.4 alkyl or C.sub.1 -C.sub.2 haloalkyl; or PA0 R.sub.2 and R.sub.3 may be taken together as --(CH.sub.2).sub.n --or --CH.sub.2 CH.sub.2 OCH.sub.2 CH.sub.2 -- or ##STR6## R.sub. is H, F, Cl or CH.sub.3 ; R.sub.5 is H, C.sub.1 -C.sub.3 alkyl, C.sub.1 -C.sub.2 alkoxy, NH.sub.2, NHCH.sub.3 or N(CH.sub.3).sub.2 ; PA0 R.sub.6 is H, C.sub.1 -C.sub.2 alkyl or phenyl; PA0 R.sub.7 is H or CH.sub.3 ; PA0 n is 2, 3, 4 or 5; PA0 p is 0 or 1; PA0 A is ##STR7## X is H, C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkoxy, C.sub.1 -C.sub.4 haloalkoxy, C.sub.1 -C.sub.4 haloalky 1, C.sub.1 -C.sub.4 haloalkylthio, C.sub.1 -C.sub.4 alkylthio, halogen, C.sub.2 -C.sub.5 alkoxyalkyl, C.sub.2 -C.sub.5 alkoxyalkoxy, amino, C.sub.1 -C.sub.3 alkylamino or di(C.sub.1 -C.sub.3 alkyl)amino; PA0 Y is H, C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkoxy, C.sub.1 -C.sub.4 haloalkoxy, C.sub.1 -C.sub.4 alkylthio, C.sub.1 -C.sub.4 alkylthio, C.sub.2 -C.sub.5 alkoxyalkyl, C.sub.2 -C.sub.5 alkoxyalkoxy, amino, C.sub.1 -C.sub.3 alkylamino, di(C.sub.1 -C.sub.3 alkyl) amino, C.sub.3 -C.sub.4 alkenyloxy, C.sub.3 -C.sub.4 alkynyloxy, C.sub.2 -C.sub.5 alkylthioalkyl, C.sub.2 -C.sub.5 alkylsulfinylalkyl, C.sub.2 -C.sub.5 alkylsulfonylalkyl, C.sub.1 -C.sub.4 haloalkyl, C.sub.2 -C.sub.4 alkynyl, C.sub.3 -C.sub.5 cycloalkyl, azido, cyano, ##STR8## m is 2 or 3; Q.sub.1 and Q.sub.2 are independently O or S; PA0 R.sub.a is H or C.sub.1 -C.sub.3 alkyl; PA0 R.sub.b and R.sub.c are independently C.sub.1 -C.sub.3 alkyl; PA0 Z is CH, N, CCH.sub.3, CC.sub.2 H.sub.5, CCl or CBr; PA0 Y.sub.1 is O or CH.sub.2 ; PA0 X.sub.1 is CH.sub.3, OCH.sub.3, OC.sub.2 H.sub.5 or OCF.sub.2 H; PA0 X.sub.2 is CH.sub.3, C.sub.2 H.sub.5 or CH.sub.2 CF.sub.3 ; PA0 Y.sub.2 is OCH.sub.3, OC.sub.2 H.sub.5, SCH.sub.3, SC.sub.2 H.sub.5, CH.sub.3 or CH.sub.2 CH.sub.3 ; PA0 X.sub.3 is CH.sub.3 or OCH.sub.3 ; PA0 Y.sub.3 is H or CH.sub.3 ; PA0 X.sub.4 is CH.sub.3, OCH.sub.3, OC.sub.2 H.sub.5, CH.sub.2 OCH.sub.3 or Cl; and PA0 Y.sub.4 is CH.sub.3, OCH.sub.3, OC.sub.2 H.sub.5 or Cl; PA0 R.sub.2 is C.sub.1 -C.sub.2 haloalkyl, OH, C.sub.1 -C.sub.2 alkoxy, NH.sub.2, NHCH.sub.3, N(CH.sub.3).sub.2, C.sub.1 -C.sub.2 alkyl substituted by C.sub.1 -C.sub.2 alkylthio, C.sub.3 -C.sub.4 cycloalkyl or C(O)R.sub.5 ; PA0 R.sub.3 is H, C.sub.1 -C.sub.4 alkyl or C.sub.1 -C.sub.2 haloalkyl; or R.sub.2 and R.sub.3 are taken together as --(CH.sub.2).sub.n -- or ##STR10## and n is 2 or 3. PA0 W is O; PA0 X is C.sub.1 -C.sub.2 alkyl, C.sub.1 -C.sub.2 alkoxy, F, Cl, Br, I, OCF.sub.2 H, CH.sub.2 F, CF.sub.3, OCH.sub.2 CH.sub.2 F, OCH.sub.2 CHF.sub.2, OCH.sub.2 CF.sub.3, CH.sub.2 Cl or CH.sub.2 Br; PA0 Y is H, C.sub.1 -C.sub.2 alkyl, C.sub.1 -C.sub.2 alkoxy, CH.sub.2 OCH.sub.3, CH.sub.2 OCH.sub.2 CH.sub.3, NHCH.sub.3, N(OCH.sub.3)CH.sub.3, N(CH.sub.3).sub.2, CF.sub.3, SCH.sub.3, OCH.sub.2 CH.dbd.CH.sub.2, OCH.sub.2 C.tbd.CH, OCH.sub.2 CH.sub.2 OCH.sub.3, CH.sub.2 SCH.sub.3, C(O)R.sub.a, ##STR11## OCF.sub.2 H, SCF.sub.2 H, OCF.sub.2 Br, cyclopropyl, C.tbd.CH or C.tbd.CCH.sub.3; and PA0 Z is CH or N. PA0 R.sub.2 is NH.sub.2, NHCH.sub.3, N(CH.sub.3).sub.2, CF.sub.3, CF.sub.2 H, OH, OCH.sub.3, CH.sub.2 SCH.sub.3, cyclopropyl or C(O)R.sub.5 ; PA0 R.sub.3 is H, CH.sub.3 or CH.sub.2 CH.sub.3; or PA0 R.sub.2 and R.sub.3 are taken together as --(CH.sub.2).sub.n -- or ##STR12## R.sub.5 is H, CH.sub.3, OCH.sub.3, NH.sub.2, NHCH.sub.3 or N(CH.sub.3).sub.2 ; and PA0 R.sub.6 is H or C.sub.1 -C.sub.2 alkyl. PA0 A is A-1; PA0 X is CH.sub.3, OCH.sub.3, OCH.sub.2 CH.sub.3, Cl, OCF.sub.2 H or OCH.sub.2 CF.sub.3; and PA0 Y is CH.sub.3, OCH.sub.3, CH.sub.2 CH.sub.3, CH.sub.2 OCH.sub.3, NHCH.sub.3 or CH(OCH.sub.3).sub.2. PA0 R is H; PA0 R.sub.1 is H; and PA0 P is O. PA0 R.sub.2 is H, C.sub.1 -C.sub.4 alkyl, CN, C.sub.1 -C.sub.2 alkyl substituted by CN or C.sub.1 -C.sub.2 alkoxy, C.sub.3 -C.sub.4 alkenyl or C.sub.3 -C.sub.4 alkynyl; PA0 R.sub.3 is H, C.sub.1 -C.sub.4 alkyl or C.sub.1 -C.sub.2 haloalkyl; or PA0 R.sub.2 and R.sub.3 are taken together as --(CH.sub.2).sub.n -- or --CH.sub.2 CH.sub.2 OCH.sub.2 CH.sub.2 --; and PA0 n is 4 or 5. PA0 W is O; PA0 X is C.sub.1 -C.sub.2 alkyl, C.sub.1 -C.sub.2 alkoxy, F, Cl, Br, I, OCF.sub.2 H, CH.sub.2 F, CF.sub.3, OCH.sub.2 CH.sub.2 F, OCH.sub.2 CHF.sub.2, OCH.sub.2 CF.sub.3, CH.sub.2 Cl or CH.sub.2 Br; PA0 Y is H, C.sub.1 -C.sub.2 alkyl, C.sub.1 -C.sub.2 alkoxy, CH.sub.2 OCH.sub.3, CH.sub.2 OCH.sub.2 CH.sub.3, NHCH.sub.3, N(OCH.sub.3)CH.sub.3, N(CH.sub.3).sub.2, CF.sub.3, SCH.sub.3, OCH.sub.2 CH.dbd.CH.sub.2, OCH.sub.2 C.tbd.CH, OCH.sub.2 CH.sub.2 OCH.sub.3, CH.sub.2 SCH.sub.3, C(O)R.sub.a, ##STR13## OCF.sub.2 F, SCF.sub.2 H, OCF.sub.2 Br, cyclopropyl, C.tbd.CH or C.tbd.CCH.sub.3; and PA0 Z is CH or N. PA0 R.sub.2 is H, C.sub.1 -C.sub.4 alkyl, CN, CH.sub.2 CN, CH.sub.2 OCH.sub.3, alkyl or propargyl; and PA0 R.sub.3 is H, CH.sub.3 or CH.sub.2 CH.sub.3. PA0 A is A-1; PA0 X is CH.sub.3, OCH.sub.3, OCH.sub.2 CH.sub.3, Cl, OCF.sub.2 H or OCH.sub.2 CF.sub.3; and PA0 Y is CH.sub.3, OCH.sub.3, CH.sub.2 CH.sub.3, CH.sub.2 OCH.sub.3, NHCH.sub.3 or CH(OCH.sub.3).sub.2. PA0 R is H; PA0 R.sub.1 is H; and PA0 p is O. PA0 R.sub.2 is C.sub.1 -C.sub.2 haloalkyl, OH, C.sub.1 -C.sub.2 alkoxy, NH.sub.2, NHCH.sub.3, N(CH.sub.3).sub.2, C.sub.1 -C.sub.2 alkyl substituted by C.sub.1 -C.sub.2 alkylthio, C.sub.3 -C.sub.4 cycloalkyl or C(O)R.sub.5 ; PA0 R.sub.3 is H, C.sub.1 -C.sub.4 alkyl or C.sub.1 -C.sub.2 haloalkyl; or PA0 R.sub.2 and R.sub.3 are taken together as --(CH.sub.2).sub.n --, or ##STR14## and n is 2 or 3. PA0 W is O; PA0 X is C.sub.1 -C.sub.2 alkyl, C.sub.1 -C.sub.2 alkoxy, F, Cl, Br, I, OCF.sub.2 H, CH.sub.2 F, CF.sub.3, OCH.sub.2 CH.sub.2 F, OCH.sub.2 CHF.sub.2, OCH.sub.2 CF.sub.3, CH.sub.2 Cl or CH.sub.2 Br; PA0 Y is H, C.sub.1 -C.sub.2 alkyl, C.sub.1 -C.sub.2 alkoxy, CH.sub.2 OCH.sub.3, CH.sub.2 OCH.sub.2 CH.sub.3, NHCH.sub.3, N(OCH.sub.3)CH.sub.3, N(CH.sub.3).sub.2, CF.sub.3, SCH.sub.3, OCH.sub.2 CH.dbd.CH.sub.2, OCH.sub.2 C.tbd.CH, OCH.sub.2 CH.sub.2 OCH.sub.3, CH.sub.2 SCH.sub.3, C(O)R.sub.a, ##STR15## OCF.sub.2 H, SCF.sub.2 H, OCF.sub.2 Br, cyclopropyl, C.tbd.CH or C.tbd.CCH.sub.3; and PA0 Z is CH or N. PA0 R.sub.2 is NH.sub.2, NHCH.sub.3, N(CH.sub.3).sub.2, CF.sub.3, CF.sub.2 H, OH, OCH.sub.3, CH.sub.2 SCH.sub.3, cyclopropyl or C(O)R.sub.5 ; PA0 R.sub.3 is H, CH.sub.3 or CH.sub.2 CH.sub.3; or PA0 R.sub.2 and R.sub.3 are taken together as --(CH.sub.2).sub.n --, or ##STR16## R.sub.5 is H, CH.sub.3, OCH.sub.3, NH.sub.2, NHCH.sub.3 or N(CH.sub.3).sub.2 ; PA0 and PA0 R.sub.6 is H or C.sub.1 -C.sub.2 alkyl. PA0 A is A-1; PA0 X is CH.sub.3, OCH.sub.3, OCH.sub.2 CH.sub.3, Cl, OCF.sub.2 H or OCH.sub.2 CF.sub.3; and PA0 Y is CH.sub.3, OCH.sub.3, CH.sub.2 CH.sub.3, CH.sub.20 CH.sub.3, NHCH.sub.3 or CH(OCH.sub.3).sub.2. PA0 R is H; PA0 R.sub.1 is H; and PA0 p is O. PA0 R.sub.2 is H, C.sub.1 -C.sub.4 alkyl, CN, C.sub.1 -C.sub.2 alkyl substituted by CN or C.sub.1 -C.sub.2 alkoxy, C.sub.3 -C.sub.4 alkenyl or C.sub.3 -C.sub.4 alkynyl; PA0 R.sub.3 is H, C.sub.1 -C.sub.4 alkyl or C.sub.1 -C.sub.2 haloalkyl; or PA0 R.sub.2 and R.sub.3 are taken together as --(CH.sub.2).sub.n -- or --CH.sub.2 CH.sub.2 OCH.sub.2 CH.sub.2 --; and PA0 n is 4 or 5. PA0 W is O; PA0 X is C.sub.1 -C.sub.2 alkyl, C.sub.1 -C.sub.2 alkoxy, F, Cl, Br, I, OCF.sub.2 H, CH.sub.2 F, CF.sub.3, OCH.sub.2 CH.sub.2 F, OCH.sub.2 CHF.sub.2, OCH.sub.2 CF.sub.3, CH.sub.2 Cl or CH.sub.2 Br; PA0 Y is H, C.sub.1 -C.sub.2 alkyl, C.sub.1 -C.sub.2 alkoxy, CH.sub.2 OCH.sub.3, CH.sub.2 OCH.sub.2 CH.sub.3, NHCH.sub.3, N(OCH.sub.3)CH.sub.3, N(CH.sub.3).sub.2, CF.sub.3, SCH.sub.3, OCH.sub.2 CH.dbd.CH.sub.2, OCH.sub.2 C.tbd.CH, OCH.sub.2 CH.sub.2 OCH.sub.3, CH.sub.2 SCH.sub.3, C(O)R.sub.a, ##STR17## OCF.sub.2 F, SCF.sub.2 F, OCF.sub.2 Br, cyclopropyl, C.tbd.CH or C.tbd.CCH.sub.3; and PA0 Z is CH or N. PA0 R.sub.2 is H, C.sub.1 -C.sub.4 alkyl, CN, CH.sub.2 CN, CH.sub.2 OCH.sub.3, allyl or propargyl; and PA0 R.sub.3 is H, CH.sub.3 or CH.sub.2 CH.sub.3. PA0 A is A-1; PA0 CH.sub.3, OCH.sub.3, OCH.sub.2 CH.sub.3, Cl, OCF.sub.2 H or OCH.sub.2 CF.sub.3; and PA0 Y is CH.sub.3, OCH.sub.3, CH.sub.2 CH.sub.3, CH.sub.2 OCH.sub.3, NHCH.sub.3 or CH(OCH.sub.3).sub.2. PA0 R is H; PA0 R.sub.1 is H; and PA0 p is O. PA0 X.sub.5 is Cl, NH.sub.2 or NHC(CH.sub.3).sub.3; PA0 R.sub.1 is H, R.sub.3 is H, R.sub.4 is H, p is O and X.sub.5 is NH.sub.2, then PA0 R.sub.2 is other than H. PA0 L is a leaving group such as Cl, Br, I, alkyl sulfide, etc.;
U.S. Pat. No. 4,544,401 discloses herbicidal pyridine sulfonylureas of the formula ##STR2## wherein R.sub.1 is NR.sub.6 R.sub.7; and
EP-A-101,670 discloses a process for the preparation of herbicidal sulfonylureas of the formula ##STR3## wherein A is --C.dbd.N--; and
U.S. Pat. No. 4,518,776 discloses a process for the preparation of herbicidal sulfonylureas of the formula ##STR4## wherein A is --C.dbd.N--; and


An apparatus and a method for determining a beam parameter of an asymmetrical photon beam generated by an accelerator are provided. A beam profile of a symmetrical photon beam is measured and normalized. For the asymmetrical photon beam, a normalization of the beam profile is implemented such that the maximum of the profile corresponds to a value of the normalized symmetrical beam profile at the site of the maximum. The parameter determination takes place using a conventional beam parameter definition.

The present embodiments relate to a method and an apparatus for determining a beam parameter of an asymmetrical photon beam generated by an accelerator.
Accelerators are used in the field of medicine for beam generation. Linear accelerators (Linacs) may be used. Linacs generate electrons or, as secondary and/or braking radiation, photons for the used beam. The generated beam may be used for both diagnostic and therapeutic purposes.
Depending on the requirements specified by the respective application, the beam of the accelerator is shaped differently. The shaping may be performed using collimation and absorption. Aside from symmetrical beam profiles (e.g., with respect to a central axis of symmetrical beams), which may result in a dose profile that is symmetrical with respect to an isocenter, asymmetrical beams are also used. For example, numerous small fields are used instead of an expanded field in beam therapy in modern irradiation techniques such as Intensity Modulated Radio Therapy (IMRT). The numerous small fields surround a tumor to be destroyed and produce a better dose distribution in the tumor.
One procedure for generating asymmetrical beams is specified in WO 98/35358, for example.
The asymmetrical beams are described and/or classified for the use.
Parameters are defined for beam description purposes. The parameters are used almost continuously in the accelerator technique. These parameters include the parameter field size (field size and/or field expansion), penumbra, symmetry and flatness. With asymmetrical fields, a displacement of the field may be performed for evaluation and/or analysis purposes such that the center of the field of the asymmetrical field lies on the central axis.

Determination of beam parameters for asymmetrical photon beams


A method for providing security for mobile device users, comprising a data service node receiving from a first device a first message directed to a web provider, inserting an anonymizing forward-to header comprising a list of anonymizing gateways; based on the list, forwarding the message to a gateway that performs anonymizing functionality and forwards the message to an embedded-scripts-extracting gateway based on the list; the embedded-scripts-extracting gateway performing an embedded-scripts-extracting functionality and forwarding the message to the web provider. The data service node also receiving from a second device a second message directed to a web provider, inserting a child-protection forward-to header comprising a list of child-protection gateways; based on the list, forwarding the message to a gateway that performs child-protection functionality and forwards it to a cookies-extracting gateway based on the list; the cookies-extracting gateway performing a cookies-extracting functionality and forwarding the message to the web content provider.

Web content is becoming more and more accessible to users by way of mobile devices. However, with this convenience comes information security threats. Online privacy is becoming an ever-growing concern. Although active measures are being taken on both the state and federal levels to develop online privacy legislation, difficulties arise in its legal enforcement. Particularly, there is no current legislation requiring website publishers and content providers (WCPs) to honor and comply with any privacy directives. Thus, even when communications service providers take active steps to implement privacy policies, their efforts may be undermined by WCPs and others seeking to collect and to monetize consumer information. For example, WCPs are acquiring consumer information by routing http messages through their gateways to extract personal information.

Dynamic insertion of service specific privacy proxy elements


Facilitating communication with automotive vehicle buses may be enabled using a vehicle gateway device (VGWD) and/or a vehicle gateway server (VGWS). In a described implementation, a VGWS may use a vehicle model database to translate requested vehicle data in a generic format from a generic data request into a vehicle-specific data format. VGWS may then send a vehicle-specific data request that has requested vehicle data in the vehicle-specific data format to a VGWD. The VGWD is able to acquire the desired vehicle data from a vehicle bus without translation using the vehicle-specific data format. The VGWD may forward the desired vehicle data in the vehicle-specific data format to the VGWS. The VGWS may then use the vehicle model database to translate the desired vehicle data in the vehicle-specific data format into desired vehicle data in a generic format. This desired generic vehicle data may be returned to a requesting entity.

Computer processors have been used in vehicles for years for specific individual functions such as for controlling anti-lock braking and climate control systems. As processor use in vehicles has evolved, processors have been proliferating across many different vehicle features and systems, including fuel adjustment, drive-by-wire, and so forth. In fact, single processors are now used for multiple functions and are often coupled to automotive vehicle buses. Hence, each vehicle now typically has one or more buses across which vehicle data is propagated.
This vehicle data may include speed, fuel level, location, and other data that is directly related to driving and/or motoring. This vehicle data may also include climate control settings, musical selections, which owner or other family member is driving, seat adjustment positions and other data that is primarily related to entertainment and/or comfort. In addition to typical in-vehicle use, this vehicle data may also be used beneficially outside the vehicle. For example, vehicle speed can be considered to indicate whether information regarding upcoming available roadside services should be delivered to a driver half a mile in advance or two miles in advance.
A module interface may be designed and installed in the vehicle at the time of manufacturing that provides certain vehicle data from the one or more vehicle buses to external entities in prescribed forms and/or at pre-set times. Each of these module interfaces are only capable of providing vehicle data in the form, at the times, and to the extent that is pre-established by the manufacturer. This limits the availability of such vehicle data to entities that are external to the vehicle.
Furthermore, automotive manufacturers tend to design and install proprietary systems and individual components for each make and model. Consequently, any such module interface is specialized and therefore that much more inflexible. These two factors separately and jointly constrain the types of services and/or communications that may be effectuated with respect to the vehicle and to the occupants thereof because access to vehicle data is inherently limited.
Accordingly, there is a need for schemes and/or techniques for exposing multiple types of vehicle data from diverse automotive vehicle buses to external entities so that tailored services may be provided to vehicles and occupants thereof.


A method and device for establishing or modifying a local IP access bearer are provided by the embodiments of the present invention, said method includes: a handover request message transmitted by an evolved Node Base station is received, said handover request message carries an evolved Node Base station identifier, said evolved Node Base station identifier is the same as the local packet data network gateway identifier; the local breakout ability of said evolved Node Base station is obtained; according to said evolved Node Base station identifier, the local breakout ability of said evolved Node Base station and the local IP access point name, the local IP access bearer is established or modified between a serving gateway and the local packet data network gateway, said serving gateway is located in the core network or the evolved Node Base station.

For a HeNB (3G Home eNodeB, 3G Home eNodeB) with local breakout ability, the local breakout bearer is established through the bearer between UE (User Equipment, User Equipment) and HeNB, the bearer between HeNB and L-SGW (Local Serving Gateway, Local Serving Gateway) and the bearer between L-SGW and L-PGW (Local PDN Gateway, Local PDN Gateway). UE will establish a local default bearer during procedures such as attaching, separating, position updating and service requesting, etc.
When UE is located within the coverage area of a HeNB cell, it can enjoy the local breakout service of the HeNB. If UE leaves the coverage area of the HeNB cell, it losses the local breakout ability and only can obtain services via a core network.
Only UEs located within the coverage area of the HeNB cell can obtain the local breakout service of the HeNB. When a UE that is using the local breakout service moves out of the coverage area of the HeNB cell, the local breakout service will be cut off. Thus, for a situation where UE needs to be continuously handed over between HeNB cell and macro-cell when UE frequently and reciprocally moves around the edge of the coverage area of the HeNB cell or when the signal over the coverage area of the HeNB cell is not stable, such discontinuity of the local breakout service will severely affect user's use of the service and thus result in user's poor experience.

Method and device for establishing or modifying local IP access bearer


Embodiments of the present invention provide a service routing method that includes: a current service routing entity receiving a service request, and the current service routing entity selecting a second service routing entity; if the second service routing entity is not the current service routing entity itself, the current service routing entity forwards the service request to the second service routing entity, sets the second service routing entity as the current service routing entity, and performs the receiving and the selecting until the second service routing entity selected by the current service routing entity is the current service routing entity itself; and if the second service routing entity is the current service routing entity itself, setting the current service routing entity as a first most adjacent service routing entity that obtains service registration information of the service and sends the service request to a service provider.

As mobile communications technologies develop rapidly, future telecom services are bound to vary and present various characteristics and complexity. Data services will take the place of voice services as the mainstream telecom services. The service servers and third-party applications are numerous. Services frequently interact and associate with each other to form a mesh structure.
In the industry, in an answer to the development trend of the broadband telecom service, each major vendor is promoting its own concept of a service delivery platform. At present, a technology and a framework are in urgent need to standardize the interaction mechanism between services, make services efficiently interact, simplify the sectors of creating and executing services, and make service operation more convenient.
In the prior art, the process of basic service routing is generally as follows: A service routing entity that receives a service request sends a service request to a home service routing entity of a service, and then the home service routing entity forwards the service request to the service requester, thereby completing service routing.
During the implementation of the basic service routing process, the inventor finds the following: The service routing entity that receives the service request must clearly know the home service routing entity of the service provider before the service request is routed to the service provider. In a self-organized networking manner, however, the home service routing entity of the service may exit the service overlay network. As such, by using the existing service routing method, the service request of the service requester may fail to be correctly routed to the service provider, resulting in service routing failure.

Service routing method and system on service overlay network


Storage stable compositions of biological materials, including bioactive biological materials are provided in the form of a water-in-oil emulsion, comprising:                (a) cellular material selected from living and/or dormant prokaryotic and/or eukaryotic cells and tissues, the cellular material being compatible with water-in-oil emulsions;        (b) one or more oils selected from vegetable oils and fish oils;        (c) an oil-soluble nonionic polymeric surfactant having a molecular weight of from about 2500 to about 15000; and        (d) water.

This invention relates to novel compositions or formulations of biological or cellular materials, including but not limited to compositions containing materials such as fungi, watermolds (Oomycetes), algae, yeasts, some bacteria, and plant, insect and animal cells, that are in the form of water-in-oil emulsions (also known as "invert emulsions"). The compositions of this invention demonstrate improved storage stability over known invert emulsions, with the material retaining viability after storage, even without refrigeration.
Materials useful in the compositions include biopesticides such as biofungicides, bioherbicides and bioinsecticides, microbial materials useful in the food, pharmaceutical, waste treatment, pulp and paper, and other industries, and, in general, plant, insect and animal cellular material. The emulsion maintains cell viability, i.e., after storage in the emulsion the stored cells can be added to media and immediately start to grow.
In more specific aspects this invention relates to novel formulations and methods of use of fungal agents such as Fusarium lateritium to control infections of plants (notably grapevines), such as Eutypa lata infections, through wounds made in cutting or pruning, and to novel formulations of entomopathogenic (insecticidal) bioactive agents such as Lagenidium giganteum and their use, for instance to control mosquitoes.
One of the most significant pathogens of the grapevine industry (whether the grapes are grown as table grapes, for raisins, or for wines) is the fungal pathogen Eutypa lata, the causative agent for Eutypa dieback, commonly known as "dying arm". This pathogen also affects other perennial crops. The disease is spread by the release of ascospores during rainfall; they enter the vascular tissue of a vine through pruning wounds, which are susceptible to infection for up to four weeks after pruning. Infections lead to yield reduction and eventual death of the vines. However, symptoms only appear after the canker is well established, which can be 2-4 years after the initial infection. When the disease is established, incidence can range upwards of 90% in 20-year-old vineyards.
E. lata infection is typically controlled by manual application of chemical or biological fungicides to pruning wounds during susceptible periods. However, this is a very labor-intensive process as the fungicide must be manually applied ("painted on") to the individual pruning wounds. Chemical fungicides typically remain viable for only about one week, so that 4-6 applications are needed each season. One fungicide that has been used for this purpose is benomyl. However, the primary manufacturer (DuPont) has withdrawn its registration of benomyl for all purposes.
Biological control has been investigated as an alternative to benomyl. Cladosporium herbarum and Fusarium lateritium have been found effective in trials. However, performance of F. lateritium had been found inconsistent in previous studies. For that reason, a combination of benomyl-resistant F. lateritium and benomyl was proposed in published U.S. patent application 2002/159980 (Block and VanderGheynst). The two members of this combination could be applied separately, or as a combined formulation, namely a solution containing benomyl in which the Fusarium cells are also suspended. However, this is no longer a viable option due to the withdrawal of benomyl from the market. An improved F. lateritium product would be very desirable as a benomyl replacement. However, to be commercially viable, such a product must have a reasonable storage life, i.e., it can be packaged, shipped and stored, while maintaining activity, for a period of time that can extend for months. In addition, F. lateritium must be applied directly to the pruning wound shortly after pruning. As mentioned earlier, this is typically done by manual "painting" of each wound.
Lagenidium giganteum is a watermold that parasitizes the larval stage of mosquitoes. It often is included in lists of fungi but nevertheless is more closely related to diatoms and brown algae. For purposes of convenience, however, the terms "fingi", "fingal", and the like, as used herein, are deemed to include L. giganteum. The life cycle begins with a motile zoospore (asexual stage) that seeks out mosquito larvae, attaching to and penetrating the cuticle via a germ tube. The fungus grows inward, eventually filling the body cavity and killing the mosquito larva. The fungus can then be released from the infected cadaver, generating more zoospores that can infect other larvae. The sexual cycle produces oospores that can maintain the fungus during unfavorable conditions, such as long periods of drought. Upon flooding, oospores release infective zoospores to start the cycle again.
A commercial product containing L. giganteum was sold for several years under the trademark Laginex® AS. This product, which no longer is on the market, was an aqueous suspension containing 40% wt./wt. L. giganteum mycelium colony forming units (CFU), a concentration measured by cell counts per liter. It was sold as a suspension for aerial spraying. One drawback of this product was the lack of long-term storage stability, a general problem with L. giganteum (see, e.g., Scholte et al., J Insect Sci. 4: 1 (2004). Additionally, the product needed to be refrigerated to maintain stability. In our work, we found that cell suspensions in aqueous systems tended towards clumping, making the resulting product uneven in composition and problematic in aerial spraying
Experience has shown that to be useful in the agrochemical or pest control field, a product must have a reasonably long storage life, including under quite different storage conditions, particularly temperature. To be easily marketed and kept available for use as needed, a product may need to withstand temperatures of 100° F. or greater, and as low as freezing. Such temperatures can be encountered in shipping or storing the products, even though attempts are made to maintain storage temperatures within a more reasonable range. Biological materials such as biopesticides are coming into use more and more with the passage of time. However, such materials are generally more sensitive to temperatures than chemicals, and so the concern over storage stability of such materials is becoming greater. Additionally, biological materials tend to have shorter shelf lives than chemical materials, even under well-controlled storage conditions. However, for marketing and distribution through the normal channels, such materials may need to be kept in storage for months, whether by the distributor, the dealer, or the purchaser.
One apparent solution to problems of storage stability would be to produce the bioactive agent in dried form and, indeed, such compositions are marketed for some bioactive agents, such as B. thuringiensis. However, drying is not suitable for all organisms. Some are too sensitive to be completely dried; others show difficulties in becoming activated or reconstituted on contact with water.
In a few cases, formulation of mycopesticides (fungal materials that act as pesticides against other organisms including other fungi and weeds) has been done in the form of so-called "invert emulsions", i.e. water-in-oil emulsions (as opposed to the much more typical oil-in-water emulsions). Such formulations are discussed, for instance, in Amsellem et al., Phytopathology 80:925 (1990), Connick et al., Weed Technology 5:442 (1991), Womack et al., Pesticide Science 37:337 (1993), Boyette et al., Weed Science 41:497 (1993), Yang et al., Phytopathology 83:953 (1993), Boyette, Weed Technology 8:526 (1994), Egley et al., Weed Science 43:312 (1995), and Womack et al., Biological Control 6:23 (1996). These works typically involved mycoherbicides contained in a water-in-oil emulsion, in which the oil often was a vegetable oil such as corn oil. A surfactant was often used, such as Myverol 18-89, a monomeric surfactant. These publications described effectiveness of the application of the pesticide in question, with the testing being done either in glasshouses or at field research stations. However, storage stability was not an essential aspect of the formulations, as they seem to have been prepared specifically for the tests in question, and so would likely not have been stored for any significant time. In addition, the invert emulsions described in such publications proved to be difficult to handle in general, and particularly difficult to spray.
In addition to use in pest control, biological materials such as fungi and the like are useful in the biotechnology, waste treatment or remediation, pharmaceutical, food, and other industries, where they may serve as catalysts, biodegradation agents, fermentation aids, and diagnostic agents among other uses. Here again, storage-stable cultures would be advantageous. Storage-stable cultures of plant, insect, and animal cells would be valuable, for more convenient preservation and storage of such materials in general.
A control agent for E. lata that can be applied directly to a pruning wound shortly after pruning, and that will have an effective life of up to 4-6 weeks, would be a very desirable product. Likewise, a product for use in controlling mosquitoes, and containing L. giganteum that that would maintain effectiveness after storage, especially if refrigeration is not required, would be very desirable.
The compositions of this invention provide such products.

Abstract: The compositions may also contain a thickener such as a hydrophobic fumed silica or bentonite.

Abstract: Compositions may be used for various purposes, depending on the contained biological material. Specific examples include compositions containing Fusarium lateritium control of Eutypa lata in plant wounds made by cutting or pruning, and compositions containing Lagenidium giganteum for control of mosquitoes.


A disc driver comprises a locking plate for locking an operation button depending upon the presence or absence of an inserted magnetic disc, and a spring bridged between a tabular leg portion of the operation button and a slide lever for absorbing a shock given to the operation button locked by the locking plate and disallowing the shock to transmit to the locking plate. In place of the locking plate, a change-over lever can be employed for enabling or disabling a function of the operation button depending or the presence of absence of an inserted disc into the disc driver.

1. Field of the Invention
The present invention relates to a disc driver for recording and/or reproducing information on or from a recording medium, in particular, a disc.
2. Description of the Prior Art
A typical one of such type disc drivers is a magnetic disc driver or a floppy disc driver which is capable of recording and/or reproducing information on or from a magnetic disc consisting of a flexible magnetic recording medium, that is, a floppy disc. This magnetic disc driver is designed to clamp a magnetic disc, load a magnetic head on the magnetic disc, or eject the magnetic disc with an operation button. And, in order to prevent a magnetic disc or a magnetic head from being damaged by an erroneous operation of the operation button, the magnetic disc driver generally employs a locking mechanism for locking the operation button when the magnetic disc is not inserted into the magnetic disc driver.
The locking mechanism or some other components, however, may be damaged if an external impact is applied on the operation button being locked. In particular, if the magnetic disc driver is assembled into a portable electronic instrument, the external impact may be more often applied on the locked operation button.
Such a shortcoming may take place in optical disc drivers and magneto-optical disc drivers in addition to the magnetic disc drivers.


The present invention encompasses a receptor molecule present on the surface of natural killer cells (NK cells) and non-specific cytotoxic cells (NCC) which is involved in non-specific lysis of target cells bearing an antigen recognized by the receptor molecule, an antigen common to the surface of cells recognized and lysed by natural killer cells, monoclonal and heterologous antibodies which bind to the receptor and target cell antigen(s) which are useful in their identification and purification, and methods for altering NK cell-mediated lysis of target cells.. The monoclonal antibodies (mAbs) of the present invention were prepared by cell fusions between spleen cells from mice immunized with either non-specific cytotoxic cells (NCC) from catfish (anti-receptor antibodies) or NC-37 human lymphoblastoid B-cells, which are susceptible to lysis by NK cells, and myeloma cells. Eight distinct mAbs have been characterized, four directed against the NK/NCC target cell receptor and four against the NK/NC cell antigen. As used in the present invention "NK cells" will be used to include both natural killer cells of mammalian origin and non-specific cytotoxic cells of fish origin, unless specifically stated otherwise. Two of the mAbs directed against the receptor and two of the mAbs against the NK target cell antigen are able to significantly inhibit NK lysis at low mAb concentrations, as assessed by inhibition of cellular toxicity. Two of the mAbs directed against the receptor and two of the mA. The U.S. government has certain rights in this invention by virtue of grants from the U.S. Department of Agriculture.

By the early 1970's, natural killer (NK) cell activity, distinct from antigen specific cytolytic T lymphocyte activity, had been reported by several laboratories in a variety of species, including mouse, rat and man. These reports are reviewed by R. K. Oldham, J. Biol. Resp. Mod. 1,217 (1982). Non-specific cytotoxic cells (NCC), similar in many aspects to NK cells, also have been identified in lower vertebrate species (Graves et al, Dev. Comp. Immunol. 8,293 (1984); Evans et al, Dev. Comp. Immunol. 8,303 (1984); Evans et al., Dev. Comp. Immuno. 8,599 (1984) Evans et al, Dev. Comp. Immunol. 8, 823 (1984).
NK cells are known to be a heterogeneous population of immune cells with regard to phenotype and function, as discussed, for example, by Lanier et al, Immunol. Today, 7,132 (1986). However, controversy still exists with regard to their lineage with respect to other immune cells and to their relationship to other effector cells such as lymphokine-activated killer (LAK) cells and anomolous killer (AK) cells. These differences may reflect the innate heterogeneity of the types of cells capable of NK activity (as defined by function) or be due to the various assay systems employed to study NK cells.
NK cells have been implicated in a variety of activities involving the immune system, including immune disorders in both animal models and man. Results from animal models have also shown that NK cells are effective in vivo against the growth and metastasis of certain types of tumors. In this regard, administration of in vitro cultured NK cells to human cancer patients has shown promise in the treatment and regression of certain types of malignancies. Further, NK cells have been implicated in host resistance to infections with microorganisms, both bacteria and viruses. Finally, NK cells are thought to play an important role in the normal regulation of the host immune system through immunoglobulin production and hematopoiesis. These lines of evidence suggest that the NK system possesses considerable functional diversity, and may operate by the recognition of changes in normal membrane structures, including differentiation antigens, as discussed by Toshitani et al, Cell Immunol.108,188 (1987); Kornbluth et al, J. Immunol. 134,728 (1985); Lauzon and Roder, Cell Immunol. 94,85 (1985); Roder et al, J. Exp. Med. 150,471 (1979).
Although NK cells have been studied for several decades, two of the major questions that remain in NK biology today are what molecule(s) on the surface of NK cells is involved in recognition of the target cells and what molecule(s) on the target cells is recognized by NK cells. At the beginning of the last decade it was found that T cells recognize products of the major histocompatibility complex (MHC) expressed on target cells. This discovery was facilitated by the availability of monoclonal antibodies (mAbs) against these molecules which inhibited their recognition by T cells. In terms of NK biology, mAb inhibition of function or recognition (in the absence of complement) has been much less frequently documented. Both the transferring receptor and the receptor for IgG Fc have been implicated to serve as recognition structures for NK cells, although these results are controversial (Vodinelich et al, Proc. Natl. Acad. Sci. USA 80,835 (1983); Dokhelar et al, Eur. J. Immunol. 14,340 (1984). The laminin/laminin receptor complex has also recently been implicated to act as a means of NK recognition of certain cells, as reported at the Fourth Int'l Workshop on NK Cells, Kingston, Ontario, 1986. Finally, carbohydrate/carbohydrate interactions have been implicated to serve as a means of NK/target cell recognition by Muchmore et al, Immunobiol. 158,191 (1981); Werkmeister et al, Cell. Immunol. 80,172 (1983). Together, these results have been interpreted as signifying that NK cells do not express clonally-restricted receptors, that NK cells may express more than one receptor on their surface and that NK cells are capable of recognizing multiple antigens on the surface of one or more target cells. These results may also be indicative of NK heterogeneity due to discrete NK subpopulations.
The NK cell membrane antigens and mAbs capable of detecting these determinants are shown in Table 1.
TABLE 1 ______________________________________ Natural killer cell membrane antigens and mAbs capable of detecting these determinants. mAb Designation Antigen Specificity ______________________________________ CD2 (Leu-5b) T cells, NK cells CD7 (Leu-9) T cells, NK cells CD8 (Leu-2) T cells, NK cells CD11 (Leu-15) C3bi receptor on T Cells, NK cells, monocytes and macrophages CD16 (Leu-11a) Fc (gamma) receptor on NK cells and on PMN's Leu 7 HNK-1 on LGL's and NK cells Leu 19 NKH-1 determinant (220 KD) on NK and T-cells .sup.a OKT8 T cytotoxic/suppressor cells and LGL OKT10 LGL, early thymus antigen 3A1 T cells and LGL 5A12 T cells and LGL Lyt 3 T cells and LGL OKT5 T cytotoxic/suppressors and LGL Ia Activated T cells ______________________________________ .sup.a Cells expressing OKT8, OKT5 and Ia are nonlytic LGL's.
Although typical NK activity is generally accepted to be mediated by cells with the Leu4- (CD3-), Leu11+ (CD16+) and Leu19+ surface phenotype, there is compelling evidence that typical T cells, particularly antigen-specific cytotoxic T cells (CTL), can mediate NK-like cytotoxicity as measured against certain tumor cells such as K562, as described by Brooks et al., Immunol. Rev. 72, 43 (1983) and others. These CTLs are referred to as CTL(NK) or non-MHC-restricted CTL. Since it has been shown that true NK cells do not transcribe mRNA for or express on their surface a typical T cell antigen receptor (TCR) (Reynolds et al, J. Exp. Med. 150,471 (1985); Lanier et al, J. Exp. Med. 163,209 (1986); Tutt et al, J. Immunol. 137,2998 (1986)), it is generally accepted that NK cells do not recognize antigen in this fashion and do not recognize MHC molecules. Although the CTL(NK) do express a typical TCR, it is not known whether this molecule is utilized to effect their NK-like killing or if these effector cells recognize MHC antigens in some aberrant fashion. Recently, there has been evidence to suggest that the CD3 molecule and the gamma/delta TCR may be involved in this type of non-MHC-restricted cytotoxicity (Farrini et al, J. Exp. Med. 166,277 (1987); Alarcon et al, Proc. Natl. Acad. Sci. USA 84,3861 (1987); Ang et al, J. Exp. Med. 165,1453 (1987); David et al, J. Immunol. 138,2831 (1987); van de Grien et al, J. Immunol.138,1627 (1987). In other studies, it has been demonstrated that anti-CD3 and anti-CD8 mAb's, while inhibiting the antigen-specific lysis by such CTL clones, do not inhibit the NK-like lysis by these effector cells (Moretta et al, Eur. J. Immunol. 14,121 (1984); Brooks and Holscher, J.Immunol. 6,594 (1987); Roberts and Moore, Eur. J. Immunol. 15,448 (1985).
Very little is known regarding identification of lymphoreticular cells in fish. Previous studies have tentatively identified a B lymphocyte subpopulation in this species. However, there have been only a few investigations where attempts have been made to identify cytotoxic cells in teleost fish. In mammals, however, a great deal is known regarding the heterogeneity of lymhocytes and mAbs have been derived which inhibit cytotoxic activity. For example, anti-OKT3 mAbs identify a determinant found on most human T cells. Monoclonal antibodies specific for this antigen inhibit CTL killing of Epstein-Barr virus infected cells. The OKT10 determinant is present on human natural killer cells as well as on other cells and anti-OKT10 mAbs inhibit NK lysis of K652, MOLT-4, and CEM tumor targets. Monoclonal antibodies directed against the glycoprotein T-200, an antigen that is present on all human peripheral blood T-lymphocytes, blocks the ability of K562 cells to inhibit NK killing of MOLT-4 cells in cold target inhibition assays. The mAb NK-8 inhibits LGL mediated cytotoxicity against K562 cells by 50 to 60%. Two mAbs (RH 7.2 and 17.2) directed against alloimmune human cytotoxic lymphocytes inhibit NK cytolysis when added at the Ca.sup.++ pulse phase.
It therefore seems apparent that in order to understand the process of NK cell recognition, it is essential to identify and characterize examples of NK target antigens, as well as the receptor(s), in a variety of species, including lower vertebrates such as fish and mammals.
Knowledge of an NK antigen receptor would enable analysis of how the receptor/ligand complex functions. Further, isolation of an NK antigen receptor would allow comparison with other receptors and possibly the identification of other NK antigen receptors or subclasses of NK cells on the basis of antigen specificity and/or type of antigen receptor. This would further understanding of the relationship between NK, LAK and CTL(NK) populations as well as immune cells such as monocytes, macrophages and other types of T cells. A comparison of the receptor molecules in fish, mouse and humans provides insights into the evolution of the NK cell population and the role they play in immune function, malignancy and immune disorders.
Knowledge of NK target antigens allows comparisons with other known ligands recognized by effector cells, such as MHC molecules, and could lead to the identification of other target antigens that may be similar in normal host defense, tumor biology and NK cell regulation. Further, as true for the NK cell receptor, identification of an NK target antigen could serve to classify NK cells into discrete subpopulations based on "antigen specificity", in that there may be subpopulations of NK cells which preferentially recognize certain target antigens. Knowledge of these molecules may have important implications concerning the types of antigen receptors present on other types of nonspecific effector cells. An analysis of the target antigen at the biochemical level may lead to a better understanding of what types of molecules are important in NK cell recognition and the role of these cells in the immune system. A comparison of the target antigens in fish, mouse and man at the biological, biochemical and molecular levels should give some insight into the evolution of the NK population in the immune system and possibly as to what challenges to the immune system this system evolved to combat. That is, if these target antigens are very conserved, at all levels of analysis, this may indicate the existence of important regulatory structures in the host and thus strong evolutionary pressures on the NK system to maintain a method by which to recognize these molecules. The anti-target cell mAb's may be of in vivo relevance in that, if NK cells are important in defense against malignancy, then an understanding of the recognition and regulation of this antigen may be useful in the detection and treatment of cancer via screening for malignancy and immune disorders, and for targeting of NK cells or mAbs to tumors.
It is therefore an object of the present invention to provide antibodies which specifically recognize and bind to antigens on the surface of NK cells and cells lysed by NK cells.
It is a further object of the present invention to provide such antibodies which can inhibit the lysis of target cells by NK cells.
It is a still further object of the present invention to provide antibodies which are useful in the isolation and characterization of NK cell populations as defined by their antigen receptors and molecules recognized thereby, as well as the actual antigens.

Antibodies to receptor and antigen for natural killer and non-specific cytotoxic cells

University of Georgia Research Foundation