The present application describes antibodies that selectively bind human FcγRIIB, with little or no binding to other human FcγRs, e.g., human FcγRIIA. The invention also provides isolated bispecific antibodies comprising an antibody that selectively binds FcγRIIB, and a second antibody that specifically binds an activating receptor. Various uses, including therapeutic uses, for those antibodies are also described, including administration with anti-tumor antibodies and methods of inhibiting immune responses and suppressing histamine release.

An antibody binds to an antigen and neutralizes it by preventing it from binding to its endogenous target (e.g. receptor or ligand) or by inducing effector responses that lead to antigen removal. To efficiently remove and/or destroy antigens foreign to the body, an antibody should exhibit both high affinity for its antigen and efficient effector functions. Antibodies having multispecificities (such as, for example, bispecific antibodies) are useful for mediating complementary or synergistic responses of multiple antigens.
Antibody effector functions are mediated by an antibody Fc region. Effector functions are divided into two categories: (1) effector functions that operate after the binding of antibody to an antigen (these functions involve the participation of the complement cascade or Fc receptor (FcR)-bearing cells); and (2) effector functions that operate independently of antigen binding (these functions confer persistence of antibody in the circulation and its ability to be transferred across cellular barriers by transcytosis). See, for example, Ward and Ghetie, 1995, Therapeutic Immunology 2:77-94. Interactions of antibodies and antibody-antigen complexes with cells of the immune system cause such responses as, for example, antibody-dependent cell-mediated cytotoxicity (ADCC) and complement dependent cytotoxicity (CDC) (reviewed in Daëron, 1997, Annu. Rev. Immunol. 15:203-234; Ward et al., supra; Ravetch et al., 1991, Annu. Rev. Immunol. 9:457-492; and Ravetch et al, 2000, Science 290:84-89.
Because Fc receptors mediate antibody effector function by binding to the Fc region of the receptor's cognate antibody, FcRs are defined by their specificity for immunoglobulin isotypes: Fc receptors specific for IgG antibodies are referred to as FcγR; Fc receptors for IgE antibodies are FcεR; Fc receptors for IgA antibodies are FcαR, and so on.
Three subclasses of FcγR have been identified: FcγRI (CD64), FcγRII (CD32), and FcγRIII (CD16). Each FcγR subclass is encoded by two or three genes that undergo alternative RNA spicing, thereby leading to multiple transcripts and the existence of a broad diversity in FcγR isoforms. The three genes encoding the human FcγRI subclass (FcγRIa, FcγRIb, and FcγRIc) are clustered in region 1q21.1 of the long arm of chromosome 1; the genes encoding human FcγRII isoforms (FcγRIIa, FcγRIIb and FcγRIIc) are in region 1q23−24; and the two genes encoding human FcγRIII (FcγRIIIa and FcγRIIIb) are clustered in region 1q22. FcγRIIC is formed from an unequal genetic cross over between FcγRIIA and FcγRIIB, and consists of the extracellular region of FcRIIB and the cytoplasmic region of FcγRIIA.
FcγRIIA encodes a transmembrane receptor FcγRIIA1. Alternative RNA splicing results in FcγRIIA2 that lacks the transmembrane region. Allelic variants of the FcγRIIA gene give rise to high responder (HR) or low responder (LR) molecules that differ in their ability to bind IgG. The HR and LR FcγRIIA molecules differ in two amino acids corresponding to positions 27 and 131. FcγRIIB encodes splice variants FcγRIIB1, FcγRIIB2 and FcγRIIB3. FcγRIIB1 and FcγRIIB2 differ by a 19 amino acid insertion in the cytoplasmic domain of FcγRIIB1; FcγRIIB3 is identical to FcγRIIB2, but lacks information for the putative signal peptidase cleavage site.
The receptors are also distinguished by their affinity for IgG. FcγRI exhibit a high affinity for IgG, Ka=108−109M−1 (Ravetch et al., 2001, Ann. Rev. Immunol. 19:275-290) and can bind monomeric IgG. In contrast, FcγRII and FcγRIII show a relatively weaker affinity for monomeric IgG Ka≦107M−1 (Ravetch et al., supra), and only interact effectively with multimeric immune complexes. The different FcγR subtypes are expressed on different cell types (reviewed in Ravetch, J. V. et al, Annu. Rev. Immunol. 9:457-492). For example, only FcγRIIIA is expressed on NK cells. Binding of antibodies to this receptor leads to ADCC activity typical of NK cells. Human FcγRIIIB is found only on neutrophils, whereas FcγRIIIA is found on macrophages, monocytes, natural killer (NK) cells, and a subpopulation of T-cells. On the other hand, FcγRII receptors with low affinity for monomeric IgG are the most widely distributed FcRs, and are usually co-expressed on the same cells. FcγRII (encoded by CD32) is expressed strongly on B cells, monocytes, granulocytes, mast cells, and platelets, while some T cells express the receptor at lower levels (Mantzioris, B. X. et al., 1993, J. Immunol. 150:5175-5184; and Zola, H. et al., 2000, J. Biol. Regul. Homeost. Agents, 14:311-316). For example, human FcγRIIB receptor is distributed predominantly on B cells, myeloid cells, and mast cells (Ravetch J. V. and et al., 2000, Science 290:84-89).
FcγRIIA and FcγRIIB isoforms contain very similar extracellular domains (approximately 92% amino acid sequence identity) but differ in their cytoplasmic regions, leading to functional differences as "activating receptors" (FcγRIIA) and "inhibitory receptors" (FcγRIIB). FcγRI and FcγRIII receptors also function as activating receptors. These activating receptors contain a 19 amino acid immunoreceptor tyrosine-based activation motif (ITAM) in the cytoplasmic domain. The ITAM sequences trigger activation of src and syk families of tyrosine kinases, which in turn activate a variety of cellular mediators, such as P13K, PLCγ, and Tec kinases. The net result of these activation steps is to increase intracellular calcium release from the endoplasmic reticulum stores and open the capacitance-coupled calcium channel, thereby generating a sustained calcium response. These calcium fluxes are important for the exocytosis of granular contents, stimulation of phagocytosis, ADCC responses, and activation of specific nuclear transcription factors.
Cellular responses mediated by activating FcγRs are regulated by the inhibitory FcγRIIB receptor in the maintenance of peripheral tolerance, regulation of activation response thresholds, and ultimately in terminating IgG mediated effector stimulation (Ravetch, J. V. et al, Annu. Rev. Immunol. 19:275-290 (2001)). Such regulation is initiated by crosslinking of activating receptors with inhibiting FcγRIIB receptors via an antigen-IgG antibody immune complex (See, for example, Ravetch, J. V. et al., 2000, supra). Crosslinking of an ITAM-containing activating receptor leads to tyrosine phosphorylation within the 13 amino acid immunoreceptor tyrosine-based inhibition motif (ITIM) in the FcγRIIB cytoplasmic domain. This "activation" of FcγRIIB initiates recruitment of a specific SH2-containing inositol polyphosphate-5-phosphatase (SHIP). SHIP catalyzes the hydrolysis of the membrane inositol lipid PIP3, thereby preventing activation of PLCγ and Tec kinases and abrogating the sustained calcium flux mediated by influx of calcium through the capacitance-coupled channel. While FcγRIIB negatively regulates ITAM-containing activating receptors (Daëron, M. et al., 1995, Immunity 3:635-646), it has also been shown to negatively regulate receptor-tyrosine kinase (RTK) c-kit in the control of RTK-mediated-mediated cell proliferation (Malbec, O. et al., 1999 J. Immunol. 162:4424-4429).
Antibodies that bind FcγRII receptors have been described in: Looney et al., (1986) J. Immunol. 136:1641-1647; Zipf et al., (1983) J. Immunol. 131:3064-3072; Pulford et al., (1986) Immunology 57:71-76; Greenman et al., (1991) Mol. Immunol. 28:1243-1254; Ierino et al., (1993) J. Immunol. 150:1794-1803. Weinrich et al., (1996) Hybridoma, 15:109-116; Sonderman et al., (1999) Biochemistry, 38:8469-8477; Lyden, T. W. et al. (2001) J. Immunol. 166:3882-3889; and International Publication No. WO 2004/016750, published Feb. 26, 2004. The high-affinity IgER1 receptor, FcεRI, mediates signaling for antigen induced histamine release upon binding of IgE during, for example, allergic reaction (von Bubnoff, D. et al., (2003) Clinical & Experimental Dermatology. 28(2):184-187). FcγRIIB receptors have been shown to interact with and inhibit the activity of FcεRI through the FcγRIIB ITIM domain (Daeron, M. et al. (1995) J. Clin. Invest. 95:577-585; Malbec, O. et al. (1998) J. Immunol. 160:1647-1658); and Tam, S. W. et al. (2004) Allergy 59:772-780). Antibodies that specifically bind human FcγRIIB are needed, not only for research, but also to manipulate FcγRIIB and FcεRI activity to treat disease.

Anti-Fc-gamma receptor antibodies, bispecific variants and uses therefor


Apparatus and methods are provided for estimating joint forces and moments in human beings. A forward dynamics module determines simulated kinematic data. An error correction controller forces tracking error between the simulated kinematic data and measured (or desired) kinematic data to approach zero. The error correction controller generates a modified acceleration for input into an inverse dynamics module. The estimated joint forces and moments track the measured (or desired) kinematics without the errors associated with computing higher order derivatives of noisy kinematic data.

A. Field of the Invention
This invention relates to human motion analysis and, more particularly, to analysis of joint forces and moments using nonlinear feedback in a forward dynamic simulation.
B. Description of Background Art
In the study of human motion, inverse dynamics analysis is conventionally used to estimate joint forces and joint moments. In a conventional inverse dynamics analysis, joint forces and joint moments are calculated from the observation of segmental movement. Inverse dynamics analysis is conventionally applied to biomechanics problems because the internal forces of human joints cannot be readily measured. Segmental movements, however, can be measured and joint angles can be inferred from the measured displacement to determine the corresponding joint forces and torques.
A problem with using inverse dynamics in the study of human motion is the error caused by calculating higher order derivatives to determine joint forces and joint moments. Methods for using inverse dynamics concepts in biomechanics are well developed if the input signals are noise-free and the dynamic model is perfect. Experimental observations, however, are imperfect and contaminated by noise. Sources of noise include the measurement device and the joint itself. Inverse dynamics methods for calculating joint moments require the calculation of higher order derivatives of the experimental observations. Specifically, the angular acceleration term is the second derivative of the joint angle and the linear acceleration is the second derivative of the center of mass acceleration. Numerical differentiation of the experimental observations amplifies the noise. The presence of high frequency noise is of considerable importance when considering the problem of calculating velocities and accelerations. The amplitude of each of the harmonics increases with its harmonic number: velocities increase linearly, and accelerations increase proportional to the square of the harmonic number. For example, second order differentiation of a signal with high frequency noise ω can result in a signal with frequency components of ω2. The result of this parabolic noise amplification is erroneous joint force and joint moment calculations.
Although techniques exist for filtering the noise, filtering is difficult and time-consuming because much analysis is required to separate the true signal in the biomechanical data from the noise. For example, low-pass filtering is commonly used to reduce high frequency errors. A difficulty in low-pass filtering, however, is the selection of an optimal cutoff frequency fc. Because there is no general solution for selecting optimal filter parameters, filtering techniques often produce unreliable results.
Optimization-based approaches have been proposed to estimate joint forces and joint moments without the errors associated with performing a conventional inverse dynamics analysis. Unlike inverse dynamics, optimization-based methods do not require numerical differentiation. However, the application of optimization-based solutions is limited because the methods are computationally expensive, are not guaranteed to converge, and are generally too complex to implement.
Another problem with using inverse dynamics for analyzing human motion is that the inverse technique lacks the capability to predict the behavior of novel motions. In inverse dynamics, forces and moments are calculated from observed responses. The prediction of novel motions involves calculating the response expected from the application of forces and moments. An inverse dynamics analysis lacks predictive capability because forces and moments are calculated rather than the expected response from the application of those forces and moments.
What is therefore needed is a computationally efficient system and method that: (1) estimates joint forces and joint moments without the errors due to higher order derivatives; (2) does not require closed form, whole body analysis; and (3) is useful for predicting the behavior of human motions.

Feedback estimation of joint forces and joint moments


This invention relates to a process for producing 5-methyl-N-aryl-2-pyrrolidone, 5-methyl-N-alkyl-2-pyrrolidone, and 5-methyl-N-cycloalkyl-2-pyrrolidone by reductive amination of levulinic acid esters with aryl or alkyl amines utilizing a metal catalyst, which is optionally supported.

Levulinic acid is a well-known product of hexose acid hydrolysis, and can be inexpensively obtained from cellulose feedstocks. Consequently, it is an attractive starting material in producing many useful 5-carbon compounds and their derivatives. For example, N-cyclohexyl-2-pyrrolidone is used as a solvent or intermediate in many industrial applications, including the electronics industry (photo-resist stripping solutions), industrial cleaners, oil/gas well maintenance, and fiber dyeing.
U.S. Pat. No. 3,337,585 discloses a process for preparing 5-methyl-1-alkyl-2-pyrrolidone utilizing levulinic acid and a primary alkyl amine at a temperature of 50° C. to 350° C. under carbon monoxide at a pressure of 1.0 to 101 MPa. Alkyl esters may also be used as a reactant with a primary amine. Additional potential primary amines include alkylene diamines, aryl amines and cycloalkyl amines. In U.S. Pat. No. 3,235,562 a vapor phase process is used for the production of lactams by reductive amination of oxo carboxylic acid or oxo carboxylic acid ester compounds. Alkyl or aryl volatile primary amines may be used.
An efficient and low cost process for the production of aryl, alkyl and cycloalkyl pyrrolidones would be advantageous.

Production of 5-methyl-N-aryl-2-pyrrolidone and 5-methyl-N-alkyl-2-pyrrolidone by reductive of levulinic acid esters with aryl and alkyl amines


Described is an apparatus comprising: a voltage level detector to monitor a first power supply node; and a voltage level protector, coupled to the voltage level detector, to protect the voltage level detector from receiving a power supply on the first power supply node above a pre-defined threshold voltage. Described is also a voltage level protector to protect a first power supply node from receiving a power supply above a pre-defined threshold voltage, the voltage level protector comprising: a first p-type device coupled to a second power supply node, the second power supply node to receive a power supply higher than the power supply on the first power supply node; and a second p-type device coupled in series to the first p-type device, the second p-type further coupled to the first power supply node, which is for coupling to a voltage level detector.

One-time programmable fuse arrays, for example, programmable read-only memories (PROMs), store various values in a Central Processing Unit (CPU) or System-on-a-chip (SoC). These stored values (also called fuse values) may relate to security keys, activation of various CPU/SoC features and functions such as cache memory size, etc. These fuse values are programmed using ultra high voltages (typically >2.2V), where the CPU may operate on a much lower voltage (e.g., 1.0V). In-Field-Programmable (IFP) fuse arrays are one-time programmable fuses that are also used for storing customer specific data (i.e., fuse values). A primary use for these IFP fuse arrays is to store specific security keys which phone devices use to function on their mobile carriers' network as well as for storing data which enables or disables any of the various functions and features of the SoC platform.
Manipulating such fuse values can unlock various features in a chip undesirably by overriding fuse values or customer security keys. One way of unlocking a processor (e.g., CPU) by disrupting fuse values is through voltage level manipulation. Voltages may be supplied from a motherboard, outside of the die and package, and are thus susceptible to manipulation through physical access of voltage pins. Changing supply voltages affects how much current can flow through a primary fuse cell as well as the reference fuse cell (which is used to develop the voltage differential at Sense Amplifier inputs), and also affect the sensing clock which controls how long the sense amplifier is enabled. This distorts the current values fed into the fuse sense amplifier as well as reduces the time required to develop the sense amplifier differential, which in turn corrupts the fuse values that are being read out.

Voltage detector with high voltage protection


A Slit-lamp-or-Microscope-Integrated-OCT-Refractometer system includes an eye-visualization system, configured to provide a visual image of an imaged region in an eye; an Optical Coherence Tomographic (OCT) imaging system, configured to generate an OCT image of the imaged region; a refractometer, configured to generate a refractive mapping of the imaged region; and an analyzer, configured to determine refractive characteristics of the eye based on the OCT image and the refractive mapping, wherein the refractometer and the OCT imaging system are integrated into the eye visualization system.

Technical Field
Embodiments disclosed herein are related to Integrated-OCT-Refractometer systems. In more detail, embodiments are related to eye-visualization systems, Optical Coherence Tomographic (OCT) imaging systems, and refractometers to determine refractive characteristics of the eye based on the OCT image and a refractive mapping.
Related Art
Current ophthalmic refractive surgical methods, such as cataract surgery, intra-corneal inlays, Laser-Assisted in situ Keratomileusis (LASIK), and photorefractive keratectomy (PRK), rely on ocular biometry data to prescribe the best refractive correction. Historically, ophthalmic surgical procedures used ultrasonic biometry instruments to image portions of the eye. In some cases these biometric instruments generated an A-scan of the eye: an acoustic echo signal from all interfaces along an imaging axis that was typically aligned with an optical axis of the eye: either parallel with it, or making only a small angle. Other instruments generated a B-scan, essentially assembling a collection of A-scans, taken successively as a head or tip of the biometry instrument was scanned along a scanning line. This scanning line was typically lateral to the optical axis of the eye. These ultrasonic A- or B-scans were then used to measure and determine biometry data, such as an ocular Axial Length, an Anterior Depth of the eye, or the radii of corneal curvature. Examples of such ultrasonic ocular biometry devices include the Alcon UltraScan and Alcon OcuScan RxP.
In some surgical procedures a second, separate keratometer was used to measure refractive properties and data of the cornea. The ultrasonic measurements and the refractive data were then combined in a semi-empirical formula to calculate the characteristics of the optimal Intra Ocular Lens (IOL) to be prescribed and inserted during the subsequent cataract phaco surgery.
More recently, the ultrasonic biometry devices have been rapidly giving way to optical imaging and biometry instruments that are built on the principle of Optical Coherence Tomography (OCT). Examples include the Zeiss IOL Master and the Haag-Streit Lenstar. Such OCT instruments are now used in 80-90% of all IOL prescription cases. Among others, their success is due to the non-contact nature of the imaging and to the higher precision than that of the ultrasound biometers.
Even with these recent advances, however, substantial further growth and development is needed for the functionalities of the biometric and imaging instruments.

Integrated OCT-refractometer system for ocular biometry


A granular ceramic is prepared by firing a powder of a natural zeolite mineral, a pre-fired powder composed of shell fragments, a pre-fired powder of a silica-alumina mineral, and a copper oxide powder. When used as a fuel additive, the ceramic makes it possible to improve the combustion efficiency of hydrocarbon oils, especially of petroleum products such as gasoline, gas oil kerosene, and heavy oil, as well as to reduce CO.sub.2 and NO.sub.x emissions in exhaust gases discharged during combustion.

1. Field of the Invention
The present invention relates to a granular ceramic for use when burning hydrocarbon oil, which makes it possible to improve the combustion efficiency of hydrocarbon oil, especially of petroleum products such as gasoline, gas oil, kerosene, and heavy oil, and to reduce unburned hydrocarbons, CO and generation of NO.sub.x emissions, and to alleviate blackened smoke fumes produced thereby, in exhaust gases discharged during combustion. The present invention also relates to a method of producing a granular ceramic for use when burning hydrocarbon oil.
2. Description of the Related Art
Various techniques for improving the combustion efficiency of petroleum products such as gasoline, gas oil, kerosene, and heavy oil have been hitherto investigated. Especially, at present, shortage of crude oil is a common problem in the world, and environmental problems are being discussed on a global scale. In such circumstances, in response to the demands for energy conservation and improvement of the environment, technological developments for efficient burning apparatuses and burning methods, as well as technological developments for the purpose of waste heat recovery are being actively performed.
When it is intended to practically use such a burning technique for energy conservation in a plant, or with equipment for production on an industrial scale, the most important problem is whether or not the investment in energy saving equipment will produce a satisfactory and cost-effective result in terms of energy savings. In the case of household oil burning machines and private automobiles used by ordinary consumers, it is undesirable if an accessory unit for energy savings excessively raises the price of the overall device as a commercial product. It is also important that such an accessory unit can be handled conveniently and safely by ordinary consumers. Taking such problems into consideration, the following suggestions have been made in order to more feasibly realize technological developments for efficient burning apparatuses and burning methods. Namely, it is a fact that combustion efficiency can be increased, and generation of unburned hydrocarbons and CO levels can be decreased, and as a result generation of blackened smoke fumes can be alleviated together with reduction in the generation of NO.sub.x emissions, by converting giant molecule groups of hydrocarbon oils into smaller molecule groups. An exemplary hydrocarbon oil, for which this technique can be implemented, is petroleum, in which several tens, hundreds, or even more hydrocarbon molecules make hydrogen bonds with each other, forming one molecule group. This fact has been confirmed by various experiments.
Known methods, which are effective as means for converting giant molecule groups of hydrocarbon oils into smaller molecule groups include 1) a method in which the hydrocarbon oils are irradiated with far infrared radiation, and 2) a method in which hydrocarbon oils are brought into contact with minerals having, for example, a high cation exchange ability, or wherein hydrocarbon oils are mixed with such minerals.

Granular ceramic for improving burning efficiency of hydrocarbon oils and method of producing the same

Tohoku Bankin Toso Kogyo Kabushiki Kaisha


A method and apparatus for the on-demand seating of a lid on pre-formed containers that are carried on a continually moving conveyor. A lid press plate (20) is connected to a linear actuator (36) by a mounting assembly (17). The mounting assembly (17) transmits a seating force from the linear actuator (36) to the lid press plate (20) for seating the lid while simultaneously allowing the horizontal movement of the lid press plate (20) from a first position to a second position by a driving force resulting solely from the application of a seating pressure between the lid press plate (20) and the lid (46). The lid press plate moves at the same velocity as the pre-formed container during application of the seating pressure. The lid press plate (20) is returned to the first position by a biasing assembly (18), after removal of the seating pressure.

1. Field of the Invention
With regard to the classification of art, this invention is believed to be found in the general class entitled Package Making and more particularly to those subclasses pertaining to the seating of a lid on a pre-formed container by means of a lid press.
2. Description of Related Art
Pre-formed containers such as molded pails, buckets and the like are used in the distribution of various products. These containers require a lid to be seated or secured thereto after a filling operation, in a processing plant.
Usually the lids are placed on the pre-formed container by a lid placing apparatus similar to U.S. Pat. No. 4,959,944, that issued to Heisler on Oct. 2, 1990, or U.S. Pat. No. 5,050,367, that issued to Heisler on Sep. 24, 1991. These patents, cited above, are illustrative of apparatus and methods for placing a lid on a pre-formed container. Each of the cited patents employ a roller compression system for seating the lids after placement. It has been found that the roller compression system may not meet the industry requirements for applying certain lids onto containers containing products that may need to be burped to reduce trapped air.
U.S. Pat. No. 5,438,814, that issued to Lovett et al on Aug. 8, 1995, attempted to address the seating of a lid on a continuously conveyed pre-formed container. However it has been found that the solution that was proposed by Lovett in U.S. Pat. No. 5,438,814 may not provide reliable results under actual manufacturing conditions. In order for the Lovett apparatus to function properly, the horizontal movement of the lid press plate must exactly match the velocity of the continually moving conveyor carrying the pre-formed container. However, it has been found that tipping of the container may occur when there is any variation between the velocity of the lid press plate and the container using the Lovett apparatus. Any tipping or jostling of the filled container prior to the full seating of the lid results in spillage of the product onto the outside of the container or onto the floor of the production area. One of the problems anticipated with the Lovett apparatus is in the timing of and/or controlling the constant velocity of the transfer cylinder that provides the horizontal movement of the lid press plate. In the Lovett apparatus the transfer cylinder must move a relatively heavy mass. That heavy mass includes at least: the carriage and the pneumatic press cylinder that are attached to the lid press plate. The transfer cylinder and its pneumatic controls are responsive to the pneumatic force in the compressed air pressure that is supplied in the manufacturing environment. Any pressure drop in the compressed air supply or pneumatic control system will effect the constant speed and response of the transfer cylinder by slowing its horizontal velocity. Any variation of the back pressure in the exhaust air control lines will also effect the velocity of the transfer cylinder. Another problem anticipated with the Lovett apparatus is in the matching of the container speed when the velocity of the conveyor may vary due to voltage fluctuations and or frictional loading at any particular time. The Lovett apparatus may require the constant attention and adjustment by an operator. Any constant attention that is required would add to the operating cost of producing the end product. Any spillage would result in product loss and resultant clean up costs and containment that would also add to operating costs.
The present invention addresses the problems identified above by exactly matching the velocity of the lid press plate to the velocity of the container at any time by allowing the container to apply a driving force to the lid press plate. Variations in conveyor speed and/or normal variations in the compressed air pressure have little or no effect on its matching of the velocity.

Method and apparatus for seating lids on continuously conveyed pre-formed containers


A torque-index sensor having index sensor and torque sensor closely arranged and integrated therein with lightened interference between them is provided. The invented torque-index sensor is comprised of torque sensor that includes first magnetic sensor arranged beside first annular-shaped magnet and index sensor that includes second magnet arranged beside annular-shaped encoder and second magnetic sensor that are arranged being in-line on common axis; and means for varying magnetic flux, which changes direction of magnetic flux that is generated from second magnet toward first magnetic sensor, positioned between first magnetic sensor in torque sensor and second magnet in index sensor.

In a power steering device of which steering motion is assisted by rotational power transmitted from a motor to steering mechanism therein, wherein the rotational power is generated by the motor responding to rotational manipulation applied over steering elements such as a steering handle, it is necessary for driving control of the steering assist motor to detect steering torque applied over the steering elements. For this detection demand, a torque sensor has conventionally been used at an intermediary position on the steering shaft that connects the steering elements and the steering mechanism.
In an electrically-assisted power steering device that uses a torque sensor, detection of the heading of steering control wheel (hereinafter referred to as steering angle) that varies according to manipulation of the steering handle, as well as the steering torque, is required for application of the steering angle to various control scheme of a vehicle.
Conventional arts have employed a mechanical rotational angle sensor for detection of the steering angle. For example, Patent Literature 1 has described a mechanical rotational angle sensor comprised of a pair of gears having different numbers of teeth each from the other, which freely rotate around an axis parallel to the steering shaft being interlocked with the turn of the steering shaft. This sensor detects the steering angle based on the data obtained by means of combining the rotation angles of each of gears of the pair sensed with a magnetic sensor.
In addition to such a mechanical sensor as is described in Patent Literature 1, an index sensor is listed as a means for detecting the number of turns of the steering shaft. The index sensor is a device that generates a reference position of rotation as the steering shaft turns.
The fundamental configuration of an index sensor will be explained referring to FIG. 5. FIG. 5 is a cross-sectional view of an index sensor installed on a steering shaft (the shaft of a steering handle) viewed in the axial direction of the steering shaft. In the index sensor 21 shown in FIG. 5, a yoke 23 made of a material having high magnetic permeability is installed on a steering shaft 4 sandwiching a collar 22 underneath. Outside of the collar 22, a magnet 211, a Hall element 212 (a magnetic sensor) that detects variation of density of magnetic flux generated from the magnet 211, and a comparator 213 that outputs reference position signal when the detected variation of density of magnetic flux becomes in excess of a predetermined threshold are arranged in line in the direction from the rotational center of the steering shaft 4 toward radially far-side.
The function of the index sensor will be explained referring to FIG. 6. In FIG. 6, such a state that the steering manipulation is not applied, i.e. the steering shaft 4 is at the reference position is shown in FIG. 6(b) and such a state that the steering shaft 4 is being turned by the steering manipulation is shown in FIG. 6(a). In the state shown in FIG. 6(b), the yoke 23 is at the position closest to the magnet 211. Since the yoke 23 is made of material having high magnetic permeability, magnetic flux 26 generated from the magnet 211 concentrates into the yoke 23 when its position is the above-stated reference position causing the magnetic flux density that the Hall element 212 will detect to be the maximum.
When the steering manipulation is applied causing the steering shaft 4 to turn, the yoke 23 shifts from the magnetic axis of the magnet 211 as shown in FIG. 6(a) with the magnetic flux 26 concentrating on the yoke 23 directed toward the opposite pole of the magnet 211 (S-pole in the figure) resulting in the Hall element 212 detecting reduced magnetic flux density. When the amount of shift of the rotational angle from the reference position becomes large to a certain extent, the flux density that the Hall element 212 detects reduces down to a certain level since the flux 26 concentrating the yoke 23 reduces.
The steering manipulation for changing the wheel traveling direction generally would not end in one turn but will end after plural turns to reach its maximum steering angle. During the course of this steering manipulation process, the magnetic flux 26 generated from the magnet 211 concentrates into the yoke 23 causing the magnetic flux density that the Hall element 212 will detect to be the maximum whenever the steering shaft 4 passes the reference position. As FIG. 5 shows, the index sensor 21 is equipped with the comparator 213 that outputs reference position signal when the detected variation of density of magnetic flux becomes in excess of a predetermined threshold. Therefore, the reference position signal is generated from the comparator 213 whenever the steering shaft 4 passes the reference position causing the magnetic flux density that the Hall element 212 will detect to exceed the predetermined threshold. That is; the number of turns of the steering shaft 4 can be detected by sensing the pass of the yoke 23 over the reference position by the index sensor 21 and by counting the number of passes over the reference position, wherein the yoke 23 is installed on the steering shaft 4 sandwiching the collar 22 underneath.
Usually, a power steering device is equipped with a motor for steering assist. Although rotation angle of this motor provides steering angle information, the information by the rotation angle of this motor is limited to the range of 0° to 360°. This means that the obtained information is relative value of angles; the absolute value of steering angle cannot be obtained from that. However, combining the information of number of turns of the steering shaft obtained by the index sensor with the information of relative value of angles obtained form the steering assist motor makes it possible to accurately find the absolute value of the steering angle caused by the steering manipulation.
Thus, the use of an index sensor enables to detect the steering angle without using such a mechanical rotational angle sensor as described in Patent Literature 1. This feature offers advantages such as reduction of number of constituent parts, simplification of fabrication process, cutting of manufacturing cost, and miniaturization of device.
{Patent Literature 1}
    Japanese Patent Application Laid-Open No. 2007-269281


A display format identification unit identifies a display format defined in a plurality of items of image data associated with each other. A message communication unit communicates a message corresponding to the identified display format when an image generation unit generates a display image in a display format different from the identified display format. A communication storage unit stores a record indicating that the message communication unit communicates a message. If the communication storage unit stores the record indicating that the message was communicated, the message communication unit does not communicate a message again.

1. Field of the Invention
The present invention relates to a technology of displaying an image.
2. Description of the Related Art
Associated with the improvement in capabilities and performance of digital cameras, a format designed to record a collection of a plurality of items of image data associated with each other is defined. The standard formulated by Camera & Imaging Products Association defines a data structure for recording a plurality of items of image data and provides a format called Multi-Picture Format that uses the data structure.
"Standard of the Camera & Imaging Products Association, CIPA DC-007-Translation-2009, Multi-Picture Format", Camera & Imaging Products Association, Feb. 4, 2009, Internet<URL:
http://www.cipa.jp/english/hyoujunka/kikaku/pdf/DC-007_E.pdf>
In the multi-picture format, "multiview" is defined as an image type. Multiview is broken down into "panorama", "stereoscopic view", and "multiangle" types. Each of the types designates a display format in a viewer. The image type is determined when the user using a digital camera to take a picture configures a photographic mode. A plurality of items of image data taken is collected by an internal circuit of the digital camera into a single image file that includes an image type code.

Information processing device and information processing method for processing and displaying multi-picture format images


A composition comprising a polymer and a phosphorescent material wherein the polymer comprises repeat units of formula (I):

Electronic devices containing active organic materials are attracting increasing attention for use in devices such as organic light emitting diodes (OLEDs), organic photoresponsive devices (in particular organic photovoltaic devices and organic photosensors), organic transistors and memory array devices. Devices containing active organic materials offer benefits such as low weight, low power consumption and flexibility. Moreover, use of soluble organic materials allows use of solution processing in device manufacture, for example inkjet printing or spin-coating.
An OLED may comprise a substrate carrying an anode, a cathode and one or more organic light-emitting layers between the anode and cathode.
Holes are injected into the device through the anode and electrons are injected through the cathode during operation of the device. Holes in the highest occupied molecular orbital (HOMO) and electrons in the lowest unoccupied molecular orbital (LUMO) of a light-emitting material combine to form an exciton that releases its energy as light.
A light emitting layer may comprise a semiconducting host material and a light-emitting dopant wherein energy is transferred from the host material to the light-emitting dopant. For example, J. Appl. Phys. 65, 3610, 1989 discloses a host material doped with a fluorescent light-emitting dopant (that is, a light-emitting material in which light is emitted via decay of a singlet exciton).
Phosphorescent dopants are also known (that is, a light-emitting dopant in which light is emitted via decay of a triplet exciton).
A hole-transporting layer may be provided between the anode and light-emitting layer of an OLED.
Suitable light-emitting materials include small molecule, polymeric and dendrimeric materials. Suitable light-emitting polymers include poly(arylene vinylenes) such as poly(p-phenylene vinylenes) and polymers containing arylene repeat units, such as fluorene repeat units. Blue light-emitting fluorene homopolymer is disclosed in WO 97/05184.
WO 2010/085676 discloses host materials for electrophosphorescent devices. A copolymer formed by copolymerization of 1,6-bis(3-(4,4,5,5-tetramethyl-[1,3,2]-dioxaborolan-2-yl)phenoxyl)hexane and 2-(4-(3-(3,6-dibromocarbazol-9-yl)propyl)phenyl)-4,6-di(3-methylphenyl)-1,3,5-triazine is disclosed.
WO 2008/025997 discloses the following monomer for use in preparation of a polymeric host:

WO 2010/136109 discloses the following intermediate compound:

Dibenzosilole polymers and applications in organic electronics are disclosed in Journal of Material Chemistry (2011), 21(32), 11800-11814.
Gaofenzi Xuebao (2009), (11), 1120-1125 discloses a polymer comprising the following monomers:

Abstract: wherein A is a heteroaryl group containing a nitrogen atom, and A may be unusubstituted or substituted with one or more substituents;    R1 in each occurrence is independently a substituent; and    n is 0, 1, 2, 3 or 4.


The present invention describes nucleic acid molecules encoding human serotonin receptors, recombinant serotonin receptor proteins, cultured cells expressing recombinant serotonin receptor proteins, antibodies immunoreactive with serotonin receptor proteins, polypeptide serotonin receptor antagonists, oligonucleotide probes used for detecting nucleic acids which encode a human serotonin receptor, and nonhuman transgenic animals which express recombinant human serotonin receptor. Also disclosed are methods for screening for ligand binding to the described serotonin receptors and for serotonin receptor agonists and antagonists, for detection of serotonin receptors in tissues, and for therapeutic treatments involving the described human serotonin receptors.

Serotonin (5-hydroxytryptamine, 5-HT) regulates a wide variety of sensory, motor and behavioral functions in the mammalian central nervous system (CNS). This biogenic amine neurotransmitter is synthesized by neurons in the raphe nuclei of the brain stem that project throughout the CNS, with highest density in basal ganglia and limbic structures. Steinbusch, Handbook of Chemical Neuroanatomy, 3:68-125, Bjorklund et al., eds., Elsevier Science Publishers, B. V., (1984). Serotonergic transmission is thought to be involved with a variety of behaviors and psychiatric disorders including anxiety, sleep regulation, aggression, feeding and depression. Cowen, British J. Psych., 159:7-14 (1991); and Lucki, Neurosci. & Biobehav. Rev., 16:83-93 (1992). Understanding how 5-HT mediates its diverse physiological actions requires the identification and isolation of the pertinent 5-HT receptors.
Molecular cloning has indicated that 5-HT receptors belong to at least two protein superfamilies: G-protein-associated receptors which have seven putative transmembrane domains (TMDs) (5-HT.sub.1A/B/C/D/E, 5-HT.sub.2 and rat stomach fundus) and ligandgated ion channel receptors which have four putative TMDs (5-HT.sub.3). Albert et al., J. Biol. Chem., 265:5825-5832 (1990); Hamblin et al., Biochem. & Biophys. Res. Comm., 184:752-759 (1992); Adham et al., Molec. Pharm., 41:1-7 (1992); Voigt et al., EMBO J., 10:4017-4023 (1991); Jin, et al., J. Biol. Chem., 267:5735-5738 (1992); Maroteaux, et al., Proc. Natl. Acad. Sci. USA, 89:3020-3024 (1992); Julius, et al., Science, 241:558-564 (1988); Lubbert, et al., Proc. Nat. Acad. Sci. USA, 84:4332-4336 (1987); Hamblin, et al., Mole. Pharm., 40:143-148 (1991); Zgombick, et al., Mole. Pharm., 40:1036-1042 (1991); Weinshank, et al., Proc. Natl. Acad. Sci. USA, 89:3630-3634 (1992); Levy, et al., J. Biol. Chem., 267:7553-7562 (1992); McAllister, et al., Proc. Natl. Acad. Sci. USA, 89:5517-5521 (1992); Pritchett, et al., EMBO J., 7:4135-4140 (1988); Foguet, et al., EMBO J., 11:3481-3487 (1992); and Maricq, et al., Science, 254:432-437 (1991).
As a serotonin receptor cloning strategy, Libert et al., Science, 244:569-572 (1989), demonstrated that novel G-protein-associated receptors could be identified in a polymerase chain reaction (PCR) using degenerate primers corresponding to strongly conserved sequences within their TMDs.
The subtypes of serotonin receptors have been historically distinguished on the basis of their pharmacological binding profiles, on second messenger coupling, and based on physiological roles known for the better characterized serotonin receptors. Most of the characterizing data in the field is not based on the properties of a single purified receptor protein or gene, but rather based on experimental observations using a model tissue. Thus, there is a need for extensive molecular and corresponding pharmacological characterization of serotonin receptors in order to better understand the extent of the subfamilies and the physiological roles each plays.


A magnetic field distribution control apparatus includes a rod portion, a coil disposed at one side of an upper surface of the rod portion, and a ferrite movably disposed within the coil and configured to produce a magnetic field.

Wireless power transmission is a technology which converts electrical energy into magnetic energy and transmits electric power without electric wires. Such a method transmits electric power based on electromotive force induced in a coil in a rod portion (e.g., battery) area, and this electromotive force is proportional to a magnetic flux interlinked with the coil. Therefore, the most important factor in determining transmission efficiency is to highly interlink magnetic flux produced by a coil in a power portion (e.g., charger) area with the coil in the rod portion (e.g., battery) area.
A transmitter using such wireless power transmission largely includes a coil, a ferrite, a variable capacitor, and the like. The ferrite is a substance which is largely used for wireless power transmission because it increases the size of a magnetic field and the inductance value of a coil.
The coil is used to induce the magnetic field while the ferrite is used to increase the size of the magnetic field. The variable capacitor is used to adjust a resonance in a drive frequency band by offsetting the inductance value of the coil.
Most ferrites used to increase the size of the magnetic field are fixed around the coil and thus the magnetic field has a fixed direction, as shown in FIGS. 1 and 2. Referring to FIG. 1, a ferrite 110 is fixed around a coil 120.
For a clear understanding, FIG. 2 is shown as a cross-sectional view taken along line I-I′ in FIG. 1. Referring to FIG. 2, the coil 120 is placed on a rod portion 130 and the ferrite 110 is airtightly located inside the coil 120. Accordingly, a magnetic field 201 is concentrated only over the ferrite 110.
In other words, such a method has good efficiency if the coil in the rod portion (battery) area is placed at a given position for charging the rod portion, but has deteriorated efficiency if the coil in the rod portion area deviates from the given position.

Magnetic field distribution control apparatus


To form and hold a loose starting flap (5) of a replacement paper roll (1) in which the replacement paper roll has a starting portion which is adhered to an underlying layer of the roll, with a simple easily made and reliable apparatus, the uppermost layer of the roll is perforated by a perforating wheel (8) or an intermittently operated laser (1008) inwardly of the end edge of the starting portion along a perforation line (3) which extends essentially parallel to the axis of the roll to form a flap portion. A temporary or permanently adhering element, such as a suction roll (912), a suction bar, an adhesively coated strip or bar (812) or a roller (912) with an adhesive surface (9, 909, 912) is moved with respect to the flap portion close to the perforation line (3). The adhering element is then moved relative to the roll, either away from the circumference, radially or otherwise, or the roll is rotated, for example in clockwise direction, so that the uppermost layer will tear at the perforation line and form a flap (5), which will be retained, by adhesion, against the adhering element.

U.S. Pat. No. 4,802,632, Fukuda, describes a method and an apparatus to handle the end portion of rolled paper on a paper roll by mechanical apparatus. The replacement roll has an end portion or initial portion adhered to the first underlying layer. This roll is mounted in the roll holder of the machine which is to handle the paper. With the roll braked, a cutter apparatus is engaged against the circumference of the replacement roll and moved transversely, in order to cut off a plurality of paper layers. These paper layers become scrap. This scrap is moved away by suction through an air suction tube to a suction transport apparatus. The suction transport apparatus then transfers the scrap paper layers to rollers which, in turn, transfer the scrap to a scrap receiving device.
This construction is expensive because it uses expensive mechanisms, and additionally, generates considerable scrap. The method has been found to be unreliable since the plurality of layers of the web must be transported by suction, and are subject to jamming in the suction conveyer. The high scrap which is generated also causes disposal problems.
German Patent 39 18 552 describes and arrangement in which only one layer of the replacement roll is cut. This requires a particular configuration of the end of the paper layers on the roll and specific positioning of the roll, as well as expensive mechanisms for cutting, positioning the roll, and sensing the initial portion. Thus, the overall mechanism is expensive.

Method and apparatus for formation and holding of a loose starting flap of a replacement paper roll, typically a paper roll in a printing machine roll changer


Chemically protected dihydroxyacetone and/or dimers are used to make polycarbonates, poly(acetal carbonate)s, poly(spiroacetal)s, polyesters and polyurethanes.

Polymeric biomaterials are in high demand for a number of biomedical and consumer applications. Two of the most prominent biomaterials are the polyesters of lactic and/or glycolic acid, and the polyanhydrides based on sebacic acid and 1,3-bis(carboxyphenoxy) propane. The number of applications for polymeric biomaterials is rapidly growing, leading to a corresponding need for the development of new kinds of biomaterials. DHA-based polymers should be an ideal candidate for this purpose. DHA is a precursor for the synthesis of glucose in humans and is also an intermediate in the metabolism of glucose in humans and is FDA-approved for topical use as the active ingredient in sunless tanning lotions. These characteristics suggest that polymers based on DHA would be advantageous materials since DHA degradation product will enter the normal metabolic pathway and minimize toxicity. However, DHA is not subject to facile polymerization because in solution its monomer is in equilibrium with its dimer, and is also reactive to primary amines. The difficulty of polymerizing DHA is evidenced by there being no publication or patent reports of a characterized polymer based on DHA.


The present invention provides an electric fence controller for delivering an electrical shock to a load when the load simultaneously contacts a fence terminal and the underlying ground. In one embodiment, the controller comprises an AC power supply and a fence terminal positioned above underlying ground. The controller also contains a voltage step-up circuit coupled to the AC power supply for charging at least one multiplier unit and for producing at the fence terminal a substantially increased DC voltage. The at least one multiplier unit discharges as an electric shock to the load when the load contacts the fence terminal and the underlying ground.

Electric fence controllers are devices that control the delivery of electric voltage and current to wire fences. Electric fences are often used to prevent the passage of animals therethrough and are particularly useful for controlling grazing animals. Of major importance in fence controllers is the ability to deliver an electric charge high enough to repel or contain an animal, yet low enough to operate safely under all conditions.
Present electric fence controllers may be classified into three groups, continuous output, pulsed output, and load-sensing fence controllers. Continuous output fence controllers provide a sinusoidally varying voltage across their output terminals. Under certain safety standards, fence controllers are considered unsafe if they deliver an electrical output having too long an on-time, too short an off-time, or too high a root-mean-square (RMS) current per pulse. Continuous output fence controllers, by definition, have a zero off-time and an indefinite on-time and, therefore, do not satisfy such safety standards. An animal or human that touches a continuously electrified fence may not be able to let go or get away from the fence, raising the possibility of delivering an unsafe shock.
The second general class of fence controllers are pulsed output controllers. U.S. Pat. No. 4,114,185, issued Sep. 12, 1978 to Gallagher, discloses such a pulsed output controller. Such pulse controllers periodically deliver a high voltage pulse to the fence. Their periodic rate is often set to conform to off-time requirements of various safety standards. Thus, pulse controllers operate more safely than do continuous output controllers.
Unfortunately, pulsed output fence controllers do not always operate effectively. For instance, during the pulse controller's off-time, an animal can slip through the fence without receiving a shock.
In an attempt to overcome this disadvantage, a third general type of controller senses and discharges when the fence load increases considerably, such as when an animal contacts the fence. When the load remains in contact with the fence, though, this supposedly improved "load-sensing" controller operates as a pulse type controller, pulsing periodically and therefore, less effectively.
Besides possible ineffective operation, another disadvantage shared by pulsed output and load-sensing fence controllers is their generation of electromagnetic noise or interference. Both types of fence controllers deliver a high voltage pulse at their output. The high frequency portions of these pulses radiate from the fence as electromagnetic energy. The resulting electromagnetic energy can interfere with nearby radio communication and other electromagnetic transmission.
In addition to reduced safety and effectiveness and generation of electromagnetic interference, another disadvantage of existing electric fence controllers is their requirement of a ground terminal. To produce a shock, fence controllers require an animal to simultaneously touch (either directly or indirectly) a hot terminal and a ground terminal. The hot terminal or fence terminal is connected to a fence wire while the ground terminal is connected to a separate ground rod embedded in the earth. Even without a ground rod connection, however, existing fence controllers can deliver a shock to an animal contacting the hot fence wire by using the animal as the path to ground. Without an adequate ground, though, the animal may not receive a shock at all, or, if a shock is delivered, a high pulse current will be returned through the neutral of the AC power supply, likely damaging the fence controller and blowing its fuses. To operate at optimum safety, existing fence controllers therefore must be coupled to ground by installing a separate ground rod and connecting it to the fence controller's ground terminal.
Current fence controllers generally require the use of step-up transformers to produce a high-voltage output. Such transformers increase the weight, cost and labor needed to produce the fence controller.

Direct capacitive discharge electric fence controller


In a combustion chamber of a gas-turbine group which essentially comprises a mixing section (2) for premixing an air/fuel mixture (16) and a downstream combustion space (3), a jump (5) in cross section is provided at the transition between the two said flow sections (2/3). This jump (5) in cross section induces the cross section of flow of the combustion space (3) and at the same time forms outer recirculation zones (10) in the combustion space (3). Flow passages (4) branch off in the end phase of the mixing section (2), which flow passages (4) then lead into the outer recirculation zones (10). A portion (9) of the air/fuel mixture flows out of the mixing section (2) through these flow passages (4) and into the outer recirculation zones (10), the portion being enriched here with an additional fuel (6). This fuel (6) is introduced via a circular line (19) provided with bores (18). The branched off mixture (9) constitutes a self-igniting pilot flame in the outer recirculation zones (10), which pilot flame substantially stabilizes the flame front (20).

1. Field the Invention
The present invention relates to a combustion chamber having fuel/air premixing.
2. Discussion of Background
In modern combustion chambers of gas turbines, premix burners which can be operated on a lean mixture are used in order to limit to a minimum the pollutant components, in particular NOx and CO, arising from the combustion. In principle, it is nowadays assumed that very low NOx emission values, below 10 vppm at 15% O2, must be ensured even at very high flame temperatures. In order to be able to achieve such low pollutant emissions during the operation of a gas turbine over a load range of about 40-100%, a perfectly premixed burner has to be ensured over a wide flame-temperature range, typically about 1650.degree.-1850.degree. K. Such burners are characterized in that a conventional air/fuel premix section is followed by a combustion chamber whose cross section of flow is several times larger than the outlet cross section of the mixing section as a result of an essentially immediate jump in cross section. As a result of this configuration, outer recirculation zones form in the combustion chamber in the region of the plane of this transition, which recirculation zones in fact induce stabilization of the premix flame. However, the stabilizing effect of these recirculation zones relative to the premix flame, i.e. relative to the backflow zone forming in the plane of the outlet cross section of the mixing section, depends substantially on how far the hot gases from the combustion can flow back into these recirculation zones in the course of operation and can maintain the feeding there to form a self-igniting combustion zone or at least a combustion zone burning in a stable manner. Especially in the transient ranges, starting, stopping, changing the operating parameters, etc., the backflow of the hot gases into the recirculation zones may take place irregularly, so that their effect on the outflowing mixture is repressed. In such a configuration, the stabilizing effect of the recirculation zones on the outflowing mixture is lost, whereupon extremely detrimental flame extinction and deflagrations may occur.


Improved methods for solution-phase synthesis of purified short-chain oligonucleotide coupling units, such as dimers, trimers, and tetramers, suitable for use in solution-phase or solid-phase oligonucleotide synthesis are provided.

Solid-phase oligonucleotide syntheses initially employed the use of phosphate triesters (the "triester method") or phosphites (the "phosphite method"). With the discovery of relatively stable mononucleoside phosphoramidite coupling units (see, for example, Beaucage and Caruthers, Tetra. Lett., 1981, Vol. 22, 1859-1862), solid-phase oligonucleotide synthesis became practical and common. Typical solid-phase oligonucleotide synthesis involves reiteratively performing four steps: deprotection, coupling, capping, and oxidation.
Standard methods involve stepwise synthesis of the oligonucleotide in the 5'-direction. In the first step ("deprotection"), the growing oligonucleotide, which is attached at the 3'-end via a 3'-O-group to a solid support, is 5'-deprotected to provide a reactive group (i.e., a 5'-OH group). For example, the 5'-OH group is often protected by reaction with 4,4'-dimethoxytrityl chloride (DMT--Cl) in pyridine, to yield a 5'-ODMT group, which is stable under basic conditions, but which is easily deprotected under acid conditions, for example, in the presence of dichloroacetic acid (DCA) or trichloroacetic acid (TCA).
In the second step ("coupling"), the 5'-deprotected supported oligonucleotide is reacted with the desired nucleotide monomer, which itself has first been converted to a 5'-protected, 3'-phosphoramidite. For example, the 5'-OH group may be protected in the form of a 5'-ODMT group and the 3'-OH group may converted to a 3'-phosphoramidite, such as --OP(OR')NR.sub.2, where R is the isopropyl group, --CH(CH.sub.3).sub.2, and R' is, for example, --H (yielding a phosphoramidite diester), or --CH.sub.3, --CH.sub.2 CH.sub.3, or the beta-cyanoethyl group, --CH.sub.2 CH.sub.2 CN (yielding a phosphoramidite triester). The 3'-phosphoramidite group of the monomer reacts with the deprotected 5'-OH group of growing oligonucleotide to yield the phosphite linkage 5'-OP(OR')O-3'. See, for example, Caruthers, M. H. and S. L. Beaucage, U.S. Pat. No. 4,415,732, issued Nov. 15, 1995.
Not all of the growing oligonucleotides will couple with the provided monomer; those which have not "grown" would yield incomplete oligonucleotides and therefore must be withdrawn from further synthesis. This is achieved by the third step ("capping"), in which all remaining --OH groups (i.e., unreacted 5'-OH groups) are capped, for example, in the form of acetates (5'-OC(O)CH.sub.3,) by reaction with acetic anhydride (CH.sub.3 C(O)--O--C(O)CH.sub.3).
Finally, in the oxidation step, the newly formed phosphite group (i.e., 5'-OP(OR')O-3') of the growing oligonucleotide is converted to a phosphate group (i.e., 5'-OP(.dbd.O)(OR')O-3'), for example, by reaction with aqueous iodine and pyridine.
The four-step process may then be reiterated, since the oligonucleotide obtained after oxidation remains 5'-protected (e.g., 5'-ODMT) and is ready for use in the first deprotection step described above.
When the desired oligonucleotide has been obtained, it may be cleaved from the solid support, for example, by treatment with alkali and heat. This step may also serve to convert phosphate triesters (i.e., when R' is not --H) to the phosphate diesters (--OP(.dbd.O).sub.2 O--), as well as deprotect base-labile protected amino groups of the nucleotide bases.
In the preparation of longer oligonucleotides, the earlier triester method offered better yields owing the availability of appropriate triester dimer and trimer coupling units (see, for example, Hirose et al., Tetra. Lett., 1978, pp. 2449-2452). However, recent developments in oligonucleotide synthesis have provided for the use of nucleotide multimers (i.e., short-chain oligonucleotides), such as nucleotide dimer phosphoramidites, as opposed to only nucleotide monomers, so as to reduce the number of required reiterations and permit both an increase in overall yield and a reduction in chemical manipulation. See, for example, Kumar and Poonian, J. Org. Chem., 1984, Vol. 49, pp. 4905-4912. For example, to obtain the oligonucleotide (dGdT).sub.10 dG, one might start with a dG-type solid-phase support (e.g., dG-CPG) and perform 10 reiterations using dGdT-dimer units (e.g., 5'-protected-dG-dT-3'-phosphoramidite), as opposed to starting with a dG-type solid-phase support and performing 20 reiterations using dG- and dT-monomer units (e.g., 5'-protected-dG-3'-phosphoramidite and 5'-protected-dT-3'-phosphoramidite).
For example, with a coupling efficiency of 99% (assumed equal for monomer and dimer couplings), twenty monomer couplings yields only (0.99).sup.20 or 81.8% yield, whereas ten dimer couplings yields (0.99).sup.10 or 90.4% yield. For a 97% coupling efficiency, the monomer and dimer yields are (0.97).sup.20 =54.4% and (0.97).sup.10 =73.7%, respectively. The ratio of the monomer to dimer yields reflects the "break even yield" required for economical synthesis of the dimer. For example, with a 97% coupling efficiency, the break even yield is 54.4/73.7=73.8%; that is, the benefits of dimer-based synthesis may be more fully realized when one is able to prepare the dimer coupling units from monomers units with 73.8% yield or greater, all other factors being equal.
For example, consider theoretically that for 20 monomer couplings, one might perform 20 steps, each step employing 1000 monomer equivalents; for the corresponding 10 dimer couplings, one would perform 10 steps, each step employing 1000 dimer equivalents, which must themselves be prepared from monomers with some inherent losses. If dimers may be synthesized from monomers with only 80% yield, then the required 10,000 useful dimer equivalents may be prepared from 25,000 monomer equivalents, as compared to the 20,000 monomer equivalents needed for monomer coupling. For a coupling efficiency of 97%, one obtains 544 correct oligonucleotides per 1000 solid-phase support sites via the 20-cycle monomer coupling method which employs 20,000 monomer equivalents (i.e., 2.72.times.10.sup.-5 oligos/site/monomer), whereas one obtains 737 correct oligonucleotides per 1000 sites via the 10-cycle dimer coupling method which employs 25,000 monomer equivalents (i.e., 2.95.times.10.sup.-5 oligos/site/monomer).
The success of these "compact" syntheses has relied on the availability of suitable dimer-phosphoramidites. For example, all sixteen di(deoxynucleotide) dimers (in the form of N-blocked-5'-ODMT-3'-2-chlorophenyl!-2'-deoxynucleotidyl-3'.fwdarw.5'!-N -blocked-2-chlorophenyl!-2'-deoxynucleoside-3'-2-cyanoethyl!phosphates) are commercially available. Typically, these dimers are prepared using a solid-phase oligonucleotide synthesis method. Consequently, use of many of the resulting dimers is relatively expensive as compared to the use of the individual monomers.
The present invention provides improved methods for solution-phase synthesis of short-chain oligonucleotides, such as nucleotide dimers, which are useful as coupling units in solution-phase or solid-phase oligonucleotide synthesis.

Selective capping solution phase oligonucleotide synthesis


A device separates foreign particles from cooling air fed to turbine rotor blades. The cooling air is fed directly or indirectly via stationary nozzle units to an annular space between wall parts of a turbine stator and rotating wheel disk as a cooling-air stream in the circumferential direction. The annular space communicates with ducts, arranged in the disk, for feeding the cooling air into the blades. A diverter unit is provided inside the annular space or so as to delimit the annular space on one side, so cooling air emerging from the nozzle units, before entering the ducts, is diverted on one side and foreign particles are centrifugally thrown into a radially outer part of the annular space and separated therefrom with a barrier-air fraction. The diverter unit has a surface region on which the stream impinges so it can be diverted radially outward through an angle greater than 90°.

A device for separating foreign particles out of a cooling-air stream which for cooling purposes is fed to a turbine rotor blade, preferably of a gas turbine installation, of the generic type is known from EP 0 690 202 B1. In the known case, cooling air is fed via stationary swirl nozzles to an annular space, which is delimited between wall parts of the turbine stator and a rotor disk, to form a turbulent flow that propagates in the circumferential direction within the annular space. The swirl nozzles each have a tangential orientation in the circumferential direction of their arrangement within the turbine stator, with the individual nozzle axes in the respective tangential plane being set obliquely with respect to the axis of rotation of the rotor arrangement, in order to form a swirling flow within the annular space.
A metal diverter plate, which is L-shaped in cross-section, is provided inside the annular space, immediately downstream of the swirl nozzles, as seen in the direction of flow; the cooling air, on emerging from the swirl nozzles, impinges perpendicularly on the longer longitudinal limb of this diverter plate, which is preferably oriented radially with respect to the rotor arrangement, and is diverted radially outward. For design reasons, the diverter plate provides, on the radially inner side with respect to the outlet opening of the swirl nozzles, a flow dead space in which foreign particles inevitably accumulate, preferably through accumulation of relatively heavy and/or large foreign particles. Deposits of this nature on the surface of the radially inner, shorter L limb lead to a risk of contamination to the cooling-air stream that forms in the annular space which should not be underestimated yet to which it is quite obvious that no further attention is paid in the above-mentioned document.
Moreover, the same document reveals a further exemplary embodiment, in which an L-shaped part, which is formed with an acute angle in cross-section, is used as the metal diverter plate, with the cooling-air stream that emerges from the swirl nozzles impinging at an angle on the longer L-limb of the diverter plate; this angle causes the cooling-air stream to be at least partially deflected radially inward. In this case, it can be assumed that the deposition of foreign particles described above will occur to an even greater extent than in the first case described.
A further device for removing dust particles from the cooling air of a gas turbine is disclosed by EP 1 174 589 A1. In the case outlined above, as it were, wall parts of the guide vane and rotor blade, positioned axially opposite one another, of a rotor arrangement delimit a type of annular space into which a cooling-air stream is introduced as swirling stream. The foreign particle separation is performed in such a manner that the cooling air that emerges from a first nozzle arrangement impinges on a type of diverter unit, by means of which the cooling-air stream is divided into a partial air stream that is directed radially outward and a partial air stream that is directed radially inward. By providing certain flow links, the radially outwardly directed partial air stream, which has increased levels of foreign particles, is passed radially outward into the hot-gas stream of the gas turbine. The accumulation of foreign particles in the radially outwardly directed partial air stream originates from the centrifugal force that acts on the foreign particles and forms as a result of the swirling flow propagating in the circumferential direction after it has passed through the swirl nozzle openings. Although it is possible to separate out relatively high-mass foreign particles using the separation method described in this document, it is impossible to rule out lightweight and smaller dust or foreign particles being entrained by the radially inwardly directed cooling-air stream for further cooling of the turbine rotor blade.

Device for separating foreign particles out of the cooling air that can be fed to the rotor blades of a turbine


Adding at least one gene involved in plant host cell T-DNA integration enhances transformation by Agrobacterium. The histone H2A gene encoded by the Arabidopsis RAT5 gene increases transformation frequencies of plants, most likely by causing overexpression of a product needed for T-DNA integration. Agrobacterium tumefaciens genetically transforms plant cells by transferring a portion of the bacterial Ti-plasmid, designated the T-DNA, to the plant, and integrating the T-DNA into the plant genome. However, not all plants are transformable by Agrobacterium and transformation frequencies may be too low to be useful. Little is known about the T-DNA integration process, and no plant genes involved in integration have been identified prior to the present invention.

The invention relates enhanced Agrobacterium transformation frequencies of plants due to overexpression of the histone H2A encoded by the Arabidopsis RAT5 gene. At present, many Arabidopsis ecotypes and mutants cannot be easily or efficiently transformed by a root transformation method, generally using Agrobacterium. Agrobacterium tumefaciens is a gram negative soil bacterium that has been exploited by plant biologists to introduce foreign DNA into plants. Although known for this practical application, the actual mechanism of DNA transfer from bacteria to plants is not completely understood. Moreover, there are some limitations on the use of this transforming vector, e.g. difficulties in transforming monocots, and transforming frequencies may be too low to be useful.
Agrobacterium tumefaciens genetically transforms plant cells by transferring a portion of the bacterial Ti-plasmid, designated the T-DNA, to the plant, and integrating the T-DNA into the plant genome. Little is known about the T-DNA integration process, and no plant genes involved in integration have previously been identified. The DNA that is transferred from Agrobacterium to the plant cell is a segment of the Ti, or tumor inducing, plasmid called the T-DNA (transferred DNA). Virulence (vir) genes responsible for T-DNA processing and transfer are reported to lie elsewhere on the Ti plasmid. The role of vir genes in T-DNA processing, the formation of bacterial channels for export of T-DNA, and the attachment of bacteria to the plant cell are reported (Sheng and Citovsky, 1996; Zupan and Zambryski, 1997). In contrast, little is known about the role of plant factors in T-DNA transfer and integration.
An international patent application (WO97/12046) describes how to improve integration of exogenous DNA by delivering the DNA into plant cells with one or more Agrobacterium genes that can encode for proteins within the plant cells. This technique, referred to as "agrolistic transformation" (p. 35) is just an improvement over biolistic transformation by which DNA is delivered to the plants by a non-biological method. In this technique, genes encoding virulence proteins that normally function in Agrobacterium are transferred to the plants along with a T-DNA substrate. The substrate is then acted upon in the plant cell to make a T-DNA molecule. The technique described does not include the use of plant genes, or of histones at all, and does not utilize histones to increase either integration of T-DNA or transformation frequency. The technique was not shown to make a plant more susceptible to transformation. The goal of WO97/12046 was to increase predictability of the location of integration, not its frequency. "Agrolistic transformation" is an expensive procedure requiring much infrastructure and resources; one of skill has to go through the laborious process every time to develop a transgenic plant.
The isolation of a putative plant factor has recently been reported. Ballas and Citovsky showed that a plant karyopherin α (AtKAP α) can interact with VirD2 nuclear localization sequences in a yeast two-hybrid interaction system, and is presumably involved in nuclear translocation of the T-complex. Using a similar approach, a tomato type 2C protein phosphatase, DIG3, that can interact with the VirD2 NLS was identified. Unlike AtKAP α, DIG3 plays a negative role in nuclear import. After the T-DNA/T-complex enters the nucleus, it must integrate into the plant chromosome. Plant chromosomal DNA is packaged into nucleosomes consisting primarily of histone proteins. The incoming T-DNA may have to interact with this nucleosome structure during the integration process. However, T-DNA may preferentially integrate into transcribed regions of the genome. These regions are believed to be temporarily free of histones. How exactly T-DNA integration takes place is unknown. Recent reports have implicated involvement of VirD2 protein in the T-DNA integration process. Plant proteins are also likely to be involved in this process (Deng et al., 1998; Ballas and Citovsky, 1997). Other suggestions for the involvement of plant factors in T-DNA transfer and integration comes from identification of several ecotypes of Arabidopsis that are resistant to Agrobacterium transformation.
Transforming the transformation resistant rat5 mutant with a wild-type RAT5 (histone H2A) gene was reported by the inventors to complement the mutant phenotype.
There are several steps in which plant genes are likely involved in the Agrobacterium-mediated transformation process. First, plant-encoded factors could be involved in the initial step of bacterial attachment to the plant cell surface. Mutants and ecotypes that are deficient in bacterial attachment have been identified, and genes involved in bacterial attachment are currently being characterized. The next step in which a plant factor(s) could be involved is the transfer of T-strands from the bacteria to plant cells across the plant cell wall and membrane. After the T-DNA/T-complex enters the cytoplasm of the plant cell, plant factors are required to transport the T-complex to the nucleus.
T-DNA integration does not appear to take place by homologous recombination, believed to be the most common method of foreign DNA integration in prokaryotes and lower eukaryotes, because no extensive homology between the T-DNA and target sequences has been found. T-DNA is reported to integrate by illegitimate recombination (Matsumoto et al., 1990; Gheysen et al., 1991; Mayerhofer et al., 1991; Ohba et al., 1995). Illegitimate recombination is the predominant mechanism of DNA integration into the genomes of higher plants (Britt, 1996; Offringa et al., 1990; Paszkowski et al, 1988).
Information on factors affecting Agrobacterium transformation frequencies in plants is needed to improve performance of this method.

This patent is subject to a terminal disclaimer.

Enhanced plant cell transformation by addition of host genes involved in T-DNA integration


According to the present, invention, when transferring a pattern of projections and valleys of a stamper to a UV curable resin coated on a disc base plate, the disc base plate is pressed against the stamper while the stamper is maintained at a constant temperature to set the viscosity of the UV curable resin to a value suitable for transferring the pattern of projections and valleys to the UV curable resin from the stamper to realize high fidelity duplication.

Heretofore, as a technique of duplicating a disc base plate of an optical disc, a magneto-optical disc etc., there is proposed a photopolymer method, a so-called 2P method, which makes use of, for example, a synthetic resin curable on irradiation of UV rays (UV curable resin).
With the 2P method, a liquid UV curable resin is applied on the surface of a disc base plate, such as by screen printing, the disc base plate is placed on a stamper so that the UV curable resin is brought into intimate contact with the stamper, the disc base plate is pressed against the stamper by a roll, the UV curable resin is cured by irradiation of UV rays and the disc base plate is peeled from the stamper simultaneously with a cured resin layer for transferring the pattern of fine projections and valleys (grooves or pits) produced on the stamper surface.
The 2P method has an advantage that, by using the liquid resin, duplication may be made faithfully without stamper deterioration and, if a glass base plate is used as a base plate, a disc base plate may be obtained which is excellent in dimensional stability and thermal resistance and low in birefringence.
For duplicating the disc base plate by the above mentioned 2P method, an apparatus comprised of a stamper 101, on the surface of which a pattern of projections and valleys in formed, a rest block 102 for securing the stamper 101 , and a centering pin 104 for peeling a disc base plate 103, on which the pattern of projections and valleys on the stamper 101 has been transferred by photocuring of the UV curable resin, from the stamper 101 , as shown in FIG. 13.
The rest block 102 functions as a supporting block for securing the stamper 101 bearing a pattern of fine projections and valleys on its surface, and also for transferring the pattern to a UV curable resin layer, not shown, provided on the disc base pl ate 103. The block 102 has a through-hole 106, at a mid position thereof, through which a shank 105 of the centering pin 104 is introduced. The block 102 is supported on a base block 108 by means of support columns 107.
The centering pin 104 functions to secure the disc base plate 103 to a predetermined site on the stamper 101 and to peel off the disc base plate 103 from the stamper 101 simultaneously with the cured resin layer. Thus the centering pin 104 is comprised of a disc-shaped head 110 fitting into a centering hole 109 formed at a mid point of the disc base plate 103 for positioning and securing the disc base plate 103 at a predetermined position on the stamper 101 and a shank 105 which is slidable along the inner peripheral surface of the through-hole 106 of the rest block 102 as a guide.
The head 110 is of substantially the same shape as the centering hole 109 of the disc base plate 103, and is adapted to be engaged in the centering hole 109 from a side facing the stamper 101 . On the other hand, the shank 105 is passed through the through-hole 106 and is connected at the lower end thereof to a pneumatic cylinder 111 provided on the base block 108 so as to be moved vertically along the inner peripheral surface of the through-hole 106 as a guide. That is, the lower end of the shank 105 fits in a recess 114 of a connecting member 113 attached to the distal end of a piston rod 112 projecting from the pneumatic cylinder 112, and is secured thereto by a bolt 115 for interconnecting the shank 105 and the pneumatic cylinder 111.
For duplicating the disc base plate with the use of the above described apparatus, the disc base plate 103 coated with the UV curable resin is placed on the stamper 101 secured to the rest block 102 so that the UV curable resin is in intimate contact with the stamper 101. At this time, the disc base plate 103 is secured at a predetermined position on the stamper 101 with a head 110 of the centering pin 104 fitting in the centering hole 109.
The disc base plate 103 is pressed by a roll, not shown, onto the stamper 101, for uniformly charging the liquid UV curable resin uniformly into a space between the stamper 101 and the disc base pl ate 103.
UV rays are then irradiated from the disc base plate side for curing the UV curable resin.
As a result, a disc base plate is produced, on the UV cured resin layer of which the pattern of the projections and valleys of the stamper 101 have been transferred.
Meanwhile, with the above mentioned 2P method, the viscosity of the UV curable resin plays a crucial role and a satisfactory transfer depends on the value of the viscosity. For example, as shown in FIG. 12, the UV curable resin is gradually increased in viscosity and lowered in fluidity as the temperature is lowered. Hence, if the disc base plate 103 coated with the UV curable resin is pressed against the stamper 101 secured on the rest block 102 maintained at an ambient temperature, the UV curable resin is increased in viscosity and becomes poor in fluidity so that the resin can not be intruded satisfactorily into interstices between the projections and valleys on the stamper. The result is that faithfulness of duplication is deteriorated. Thus the UV curable resin has a range of viscosity which is suited to transfer and which needs to be maintained by some means or other.
In view of the above described status of the prior art, it is an object of the present invention to provide a disc transfer method whereby the pattern of projections and valleys of the stamper may be transferred satisfactorily to a UV curable resin layer.


A control system comprising an NH3 storage level determination module that determines an NH3 storage level in an exhaust system, and a fuel control module that controls an air-to-fuel (A/F) ratio in an engine based on the NH3 storage level. A method comprising determining an NH3 storage level in an exhaust system, and controlling an A/F ratio in an engine based on the NH3 storage level.

The background description provided herein is for the purpose of generally presenting the context of the disclosure. Work of the presently named inventors, to the extent it is described in this background section, as well as aspects of the description that may not otherwise qualify as prior art at the time of filing, are neither expressly nor impliedly admitted as prior art against the present disclosure.
Internal combustion engines may be operated at a lean air-to-fuel (A/F) ratio to improve fuel economy. Nitrogen oxide (NOx) emissions produced during lean operation are controlled. Selective catalytic reduction (SCR) catalysts, dosing systems, and lean NOx trap (LNT) catalysts are commonly used with internal combustion engines for emissions reduction.
In a typical SCR process, NOx reacts with a reductant which is injected by the dosing system into the exhaust gas stream to be absorbed onto an SCR catalyst. The injected dosing agent (e.g., urea) breaks down to form ammonia (NH3). NH3 reacts with NOx to reduce NOx into nitrogen (N2) and water (H2O).
LNT catalysts may absorb NOx from exhaust gas when the SCR unit cannot effectively reduce NOx emission during an engine start-up period. LNT catalysts may release the absorbed NOx after the exhaust gas reaches a predetermined temperature where the SCR unit can effectively convert NOx into N2 and H2O. As a result, NOx emission released to the atmosphere during the engine start-up period may be reduced.

Lean nitrogen oxide emission control system and method


Provided herein, inter alia, are compositions and methods for generating a immune response in an individual and/or inducing the expression of neoantigens on the surface of abnormal (such as proliferative) cells via inhibition of nonsense-mediated decay (NMD) of messenger RNAs (mRNAs) bearing premature termination codons (PTCs).

Despite the progress made in the development of cancer therapeutics over the past two decades, treatments based on inducing the immune system to attack abnormally proliferating cells have had only limited success in slowing tumor progression, including progression to metastatic disease. One reason for this lies in the fact that the naturally occurring response by the immune system to cancer cells is weak, in part because cancer cells do not generally express antigens that the immune system recognizes as foreign. For the most part, conventional cancer vaccines rely on weakly immunogenic antigens expressed on tumor cells in order to bring about an immune response throughout the body. However, even the best cancer vaccines are effective at only temporarily delaying disease progression and very few have been shown capable of reversing it.
As such, there is a particular need for improved compositions and methods for inducing the expression of neoantigens on the surface of cancer cells. Such novel antigens would be capable of bringing about a potent immune response in an individual leading to the destruction and elimination of the cancer cells throughout the individual's body.
Throughout this specification, various patents, patent applications and other types of publications (e.g., journal articles, electronic database entries, etc.) are referenced. The disclosure of all patents, patent applications, and other publications cited herein are hereby incorporated by reference in their entirety for all purposes.

Methods for inducing an immune response by inhibition of nonsense mediated decay


The present invention is directed to a unique foldable winglet assembly adaptable for use with an aircraft for maximizing the wing span of the aircraft during cruise operation while reducing wing bending moment during extreme flight maneuvers. A foldable winglet is pivotally joined to the aircraft wing and is rotatable during flight between a retracted position and a fully extended position. An actuator is mounted on the aircraft wing and attached to the foldable winglet. When the aircraft reaches cruise operation, the actuator can be manually or automatically energized to pivot the winglet from a substantially vertical, retracted position to a fully extended position wherein the winglet becomes an extension of the wing. During cruise, the wing and winglet form an enlarged wing that serves to maximize lift of the aircraft. When loads more severe than would occur at or near cruise, such as dive, are encountered, the loads overcome the action of the actuator and pivot the winglet to its initial, vertical position. This action, serves to reduce the bending moment acting on the wing as well as increase aerodynamic efficiency of the aircraft.

The present invention relates generally to the concept of airplanes having folding winglets, and more particularly, to winglet assemblies which can be extended during cruise to increase span and automatically/passively retracted to an upright position as needed to reduce the wing bending moment and aircraft weight when subjected to large loads at conditions such as dive.
Because of the reduced size of the flight deck and reduced hangar space, it has long been known to fold the wings of fighter aircraft when stored onboard aircraft carriers. Such aircraft normally include a power driven actuator system which functions to move an outboard portion of the aircraft wing between an extended position suitable for flight and a retracted storage position. U.S. Pat. No. 5,310,138 entitled "Wing Fold Actuator System for Aircraft" issued May 1994 to Thomas F. Fitzgibbon is believed to be typical of such an aircraft. It is noted that the actuator system is provided to pivot the wing from a folded position when stored to an extended position prior to flight. The disclosure of the '138 patent is herein incorporated by reference. There is no suggestion in the '138 patent of pivoting the wing between deployed and retracted positions during operation of the aircraft.
It is known that having an aircraft's winglets extend at an angle to the remaining portion of the wing can affect the flight characteristic of the aircraft. U.S. Pat. No. 5,072,894 entitled "Apparatus and Method for Increasing the Angle of Attack Operating Range of an Aircraft" issued December 1991 to Daniel R. Cichy, the disclosure of which is herein incorporated by reference, teaches that the by employing vertically downwardly extending tip fins, it is possible to increase the angle of attack operating range of an aircraft. At high angles of attack, the tip fins extend approximately 90.degree. to the inboard portion of the wing. There is no suggestion of raising the tip fins above the wing nor is there any suggestion of extending the tip fins during flight.
Commercial aircraft have been known to employ foldable wing tips which can be raised to reduce the landing space occupied by the aircraft. By raising the wing tips, aircraft having large wings, such as the Boeing 777, can reach current loading gates that would otherwise be unavailable. A latching mechanism for locking the wing tips in their upright position when on the ground is taught in U.S. Pat. No. 5,427,329 entitled "Locking Hydraulic Latch Pin Actuator" issued June 1995 to Michael E. Renzelmann et al, the disclosure of which is herein incorporated by reference. A hydraulic actuator is employed to move the primary lock member between locked and unlocked positions when the aircraft is on the ground. There is no suggestion in the '329 patent that the wing tips are movable when the aircraft is in flight.
None of the cited patents employs a wing including a foldable winglet that can be folded while the aircraft is in flight. As a result, none of the cited patents can take advantage of the extended winglets during cruise and folded winglets during more severe load conditions.
The present invention overcomes the size and structural weight problems associated with a large span while retaining the reduced drag benefit of a large span during cruise.


A mask forming method includes preparing design data of mask including pattern regions having identical repetition patterns respectively, generating mask pattern data of mask based on the design data, generating inspection control information for controlling inspection of defect on mask based on the mask pattern data, the information including positional information of the pattern regions and inspection sensitivity information of the repetition pattern, providing the inspection control information to mask pattern data, forming mask pattern of mask based on the mask pattern data, and inspecting the mask pattern based on the mask pattern data comprising inspecting portion in the mask pattern different from the pattern regions by Die-to-Database comparison method, the inspecting the portion including selecting portion corresponding to repetition pattern from the mask pattern based on the positional information, and inspecting the selected portion by Die-to-Die comparison method at an inspection sensitivity corresponding to inspection sensitivity information.

1. Field of the Invention
The present invention relates to a mask forming method and a semiconductor device manufacturing method used in lithography process of semiconductor process.
2. Description of the Related Art
In recent years, the downsizing of semiconductor devices has been in progress. As a result, in a mask manufacturing process, a correction process for correcting an optical proximity effect (OPC: Optical Proximity Correction) has been carried out. By the OPC process, fine graphics such as fine pattern steps or fine pattern irregularities are formed on design data.
Mask pattern data at the time of forming a mask pattern (data obtained by applying a required process such as an OPC process for design data) includes data that corresponds to fine graphics.
However, fine graphics are not always reflected faithfully on a pattern (mask pattern) actually formed on a mask. Therefore, the degree of faithfulness of a mask pattern relevant to mask pattern data (degree of pattern forming faithfulness) is lowered at a portion of the mask pattern that corresponds to the fine graphics.
In recent years, a mask pattern has been inspected at a high sensitivity of defect detection. Thus, there has been established a situation in which the lowered degree of pattern forming faithfulness cannot be ignored in guaranteeing an inspection result.
For example, in a mask defect inspection of Die-to-Database comparison method (Jpn. Pat. Appln. KOKAI Publication No. 2002-23345), the following problem occurs due to the lowered degree of pattern forming faithfulness.
In the mask defect inspection of the Die-to-Database method, the presence or absence of a defect in a mask pattern is checked with a desired sensitivity of defect detection by comparing the mask pattern and mask pattern data with each other.
Here, in the case where, due to the lowered degree of pattern forming faithfulness, a difference between the mask pattern and the mask pattern data exceeds a critical condition (thresholds indicating whether or not a defect is observed) for the severest defect detection sensitivity (corresponding to a detected minimum defect size) at a portion of the fine graphics formed by OPC process, the portion of the fine graphics formed by OPC process is recognized as a defect.
The above described defect is a harmless defect from the viewpoint of device guaranteeing (hereinafter, referred to as a false defect). There is no need for correcting the false defect. For this reason, a work of classifying a plurality of detected defects into false defect and true defect (harmful defect from the viewpoint of device guaranteeing) is carried out.
In this classifying work, a workload increases due to a trend for downsizing semiconductor devices. Part of the classifying work is automated. However, the automated classifying work is still poor in reliability. Therefore, there has not been established a situation in which a classifying work by visual inspection can be eliminated.
Under such a situation as described above, a tremendous number of false defects occur in one mask due to the downsizing of a pattern and due to the downsizing of an OPC correction grid (correction unit). Specifically, false defects may occur in number exceeding an upper limit of defects in number that can be maintained (stored) in a defect inspection apparatus. In this case, there has been established a situation in which the whole mask cannot be inspected.
An inspection capable of reducing the number of detected false defects includes a mask defect inspection by Die-to-Die comparison method. This inspection selectively extracts regions formed by the same pattern group from the all of patterns formed on one mask, and comparatively checking detection signals between the extracted regions, thereby detecting a defect.
However, in general, a pattern forming region of one mask is not formed of only the same pattern group, and all the defects in a desired region of the mask cannot always be detected by only the defect inspection of the Die-to-Die comparison method.

Semiconductor mask inspection using die-to-die and die-to-database comparisons