It is well known that interlaced video result in flicker artifacts that are annoying and tiring for the viewer. The technology for displaying progressive video have improved over the years and is now feasible. At the same time digital video compression have also advanced with the introduction of MPEG2 standard. However digital progressive video requires a lot of processing power. A method of decoding compresses digital video of a progressive video sequences at 60 frames per second using multiple decoders operating at 30 frames per second is disclosed in this invention. This invention describes the method and apparatus by which the compress digital video bitstream can be partition into independent units that can be decoded by the multiple decoders in parallel.

1. Field of the Invention
The present invention relates to the field of digital video compression and decoding. In particular it enables a compressed video bitstream to be decoded by multiple decoders each of which has a lower decoding frame rate capability than that of the target display frame rate.
2. Related art of the Invention
Most video material today are available in interlaced format at 60 fields per second. Interlaced format introduces many artifacts such as screen flicker that are annoying to the viewer. With current display technology it is now possible to display progressive format at 60 frames per second. This means that the viewer need not have to content with the interlace artifacts. In fact by using progressive format the subjective image quality is improved significantly.
MPEG 2 is the latest international standard for coding digital video. The digital video is compressed into bitstreams that can be decoded by a decoder for display. Using the Main Profile at High Level it is possible to code progressive video at 60 frames per second. The current invention deals with the method for achieving the above decoding method.
Currently decoder chips conforming to the Main Profile at Main Level are available and are able to decode compressed bitstream at up to 30 frames per second. In order to decode at twice the frame rate required by the progressive format a faster decoder have to be designed. On the other hand, the mismatch in the decoding and display frame rate can be solve by using more than one decoder in parallel. However the solution is not as trivial as simply to put two decoders together and dividing up the bitstream among the decoders. The reason is that the compressed bitstream is organized in groups of pictures, GOP, and each GOP contains intra coded pictures, I-pictures, forward predicted pictures, P-pictures, as well as bidirectionally coded pictures, B-pictures. This is depicted in FIG. 1 which shows the organization of the bitstream for the I-, P- and B-pictures in transmission order starting from left to right.
It is not possible to simply assign one GOP to one decoder because the decoding of the first two B-pictures in the GOP requires the reference to the last P-picture of the previous GOP as shown in FIG. 2. Similarly it is not feasible to partition the bitstream at the position indicated by the arrow in FIG. 2 as the P-picture after the arrow requires the reference to the preceding I-picture. Since more than one decoder is used in parallel, and each decoder only receives its share of the bitstream the reference picture will not be available at the boundary where the bitstream is partitioned. If we simply duplicate the bitstream then there will be a duplication of the I-picture and B-pictures at the boundary of the GOP.

Method and apparatus for partitioning compressed digital video bitstream for decoding by multiple independent parallel decoders

Matsushita Electric Industrial Co., Ltd.


Methods of preparing a carbon doped oxide (CDO) layer with a low dielectric constant (<3.2) and low residual stress without sacrificing important integration properties such as refractive index and etch rate are provided. The methods involve, for instance, providing a substrate to a deposition chamber and exposing it to TMSA, followed by igniting and maintaining a plasma in a deposition chamber using radio frequency power having high and low frequency components or one frequency component only, and depositing the carbon doped oxide film under conditions in which the resulting dielectric layer has a net tensile stress of less than about 40 MPa, a hardness of at least about 1 GPa, and a SiC:SiOx bond ratio of not greater than about 0.75.

There is a general need for materials with low dielectric constants (low-k) in the integrated circuit manufacturing industry. Using low-k materials as the interlayer dielectric of conductive interconnects reduces the delay in signal propagation and signal crosstalk due to capacitive effects. Further, the use of low k materials as interlayer dielectrics reduces power consumption of complex integrated circuits.
Low-k dielectrics are conventionally defined as those materials that have a dielectric constant (k) lower than that of silicon dioxide (SiO2), that is k<˜4. Generally, they have a dielectric constant of 3.2 or less. Typical methods of obtaining low-k materials include introducing pores into the dielectric matrix and/or doping silicon dioxide with various hydrocarbons or fluorine. In technology nodes of 90 nanometers and beyond, carbon doped oxide dielectric materials look extremely promising. However, wide spread deployment of these materials in modern integrated circuit fabrication processes presents some technological hurdles.
Specifically, in comparison with silicon dioxide, low k CDO materials typically have inferior mechanical properties due to the incorporation of ending methyl groups (—CH3) in order to lower the k value of CDO materials. These mechanical properties include hardness, modulus, film residual stress, blanket film cracking threshold or limit, fracture toughness, etc. These properties are derived primarily from the strength of the atomic bonds and their binding energy. For instance, when using conventional Si containing organics as precursors in a conventional plasma enhanced chemical vapor deposition (PECVD) process, the resulting dielectric CDO film will usually possess a dielectric constant of 2.7-2.95 with a hardness of 1.2-2.0 GPa, modulus of 6.6 to 12 GPa, and a blanket film cracking limit between 2.3-2.7 μm. It is noted that the cracking limit is an overall measure of mechanical properties of a CDO film. Many applications will require cracking thresholds of greater than 3 μm, and more preferably greater than 5 μm. CDO materials of inferior mechanical properties will have adhesive (delamination) and cohesive (cracking) failures during the Cu-low k integration and packaging steps. These failures are exacerbated by the increasing complexity of integrated circuits and manifest as growing numbers of metallization layers. It is not uncommon for a modern IC design to require nine metallization layers, each with a separate dielectric layer. Each of these dielectric layers will have to withstand mechanical stresses from, for example, Chemical Mechanical Polishing (CMP) and/or thermal and mechanical stresses incurred during IC packaging operations.
In addition to modulus, a mechanical property of growing importance is the residual (or internal) stress in a dielectric film. As explained below, residual stress is comprised of an extrinsic stress component and an intrinsic stress component. Further, residual stress can be either compressive or tensile. Conventional low k films (k<3.2), including CDO films, typically have a tensile stress in excess of 50 MPa. The residual stresses within a deposited dielectric film are of particular interest for this invention. In IC fabrication contexts, these stresses can manifest in different ways, including cracking initiation and propagation and bowing or arching of die, which indicate net tensile or compressive stress. Low residual stress leads to a low cracking driving force, a high cracking or buckling limit and hence a low failure rate during Cu-low k integration and packaging.
Many device failures can ultimately be traced to stresses and their variations at various stages of IC processing. Those failures include interfacial delamination between different materials and cracking within one material during chemical mechanical polishing (CMP) and packaging. Excessive stress of thin films, such as CDO films, will also accumulate through multiple layer integration and will result in wafer warping and CMP issues. Since device feature size is continuously shrinking, stress related problems are expected to become more severe.
Thus, there is a need for low-stress dielectric films. However, methods that create lower stress CDO films often produce films with significantly different chemical properties than the CDO films in use in many current applications. Generally, the suitability of a low dielectric constant film can be determined by the ease with which it can be integrated into an interconnect stack. Ideally, it is desirable that low-stress films have comparable etch rates when compared with existing low-k material layers. Some current methods of creating low-stress CDO films result in low-k films with refractive indices/etch rates which are very similar to oxygen doped carbide materials which are often used as barrier layers, resulting in comparable etch rates for barrier layers and low-k material layers-potentially complicating integration and creating a need for new integration schemes. Thus, there is a high demand for methods that will produce low-stress, low-k CDO films with refractive indices/etch rates similar to existing conventional low-k films.
To achieve the foregoing, methods of improving the mechanical properties of thin films, including CDO films, are disclosed. Further, this invention relates to techniques for creating low-stress, low-k carbon-doped oxide (CDO) layers by modifying the CDO film's structure using chemical bond reconstruction to alter SiC/SiO ratios such that the refractive index/etch rate of the CDO material is similar to that of existing conventional low-k films. In particular, this invention presents methods to modify the film structure of a low-stress CDO film without an appreciable loss in film performance, thus allowing easier integration of low-stress CDO films into an interconnect stack.
In one embodiment of the invention, a carbon doped silicon oxide (CDO) film is deposited on a substrate by contacting the substrate with one or more CDO precursors having a high carbon content to form a CDO film with a SiC:SiOx bond ratio of not greater than about 0.75, a net tensile stress of less than about 40 MPa, a hardness of at least about 1 GPa, and a dielectric constant of less than about 3.2.
In some embodiments, the CDO film is formed on the substrate by a chemical deposition process (for example PECVD), using one or more precursors carried in a carrier gas such as CO2, Ar, or He. In a specific implementation, the CDO precursor is Ethynyltrimethylsilane (ETMS), also known as trimethylsilaneacetylene (TMSA).
In other embodiments, a secondary precursor is added. In one implementation diethoxymethylsilane (DEMS) and/or tetramethylcyclotetrasiloxane (TMCTS) are added. Further, in one or more of these embodiments, another reactant, hexafluoroethane (C2F6), is introduced into the deposition chamber.
Flow rates of the various precursors, carrier gases, and reactants vary broadly. A typical flow rate for TMSA is the range of between about 0.3 mL/min to 10 mL/min, preferably in the range of between about 2.5 mL/min to 3.5 mL/min. If DEMS is added, the flow rates range broadly from between about 0.3 mL/min to 5 mL/min for each and more preferably in the range of between about 1.5 mL/min to 2.5 mL/min for each. If TMCTS is added, the flow rates range broadly from 1 mL/min to 3 mL/min and more preferably in the range of 1 mL/min to 2 mL/min. The flow rate of O2 ranges broadly between about 100 mL/min to 1000 mL/min, more preferably in the range of 100 mL/min to 400 mL/min. The flow rate for hexafluoroethane varies between about 0 mL/min to 1000 mL/min, preferably between about 0 mL/min to 500 mL/min.
The flow rates of the various carrier gases range broadly as well. For CO2, the broad range is between about 1000 sccm to 15000 sccm, while the preferred range is between about 1500 sccm to 8000 sccm. In some embodiments, Ar and He are substituted for CO2. When Ar and/or He are added, flow rates range broadly from between about 1000 sccm to 10000 sccm for each and, more preferably, between about 1500 sccm to 2500 sccm for He and 1500 sccm to 3500 sccm for Ar. In embodiments where Ar and/or He are added, He and Ar flow rates may be the same or different.
In another embodiment of the invention, an integrated circuit (IC) with one or more CDO dielectric layers having carbon-carbon triple bonds or both and/or their derivative forms generated during the deposition is provided. In some embodiments, the CDO layer serves as an interlayer dielectric in the IC. In a preferred embodiment, the CDO dielectric layer has a dielectric constant of less than about 3.2, a net tensile stress of less than about 40 MPa, a hardness of at least about 1 GPa, and a SiC:SiOx bond ratio of not greater than about 0.75.
In still another embodiment, deposited CDO films have a SiC:SiOx bond ratio of between about 0.2 to 0.7, a SiH/SiOx bond ratio of between about 0.01 to 0.18, and a refractive index (RI) of 1.4-1.65 measured at 633 nm.
These and other features and advantages of the invention will be presented in more detail below with reference to the associated drawings.

This patent is subject to a terminal disclaimer.

Methods for producing low-stress carbon-doped oxide films with improved integration properties


A process for producing methanol reduces the emission of carbon dioxide which is responsible for global warming. The process involves the steps of generating steam by the use of nuclear heat of a high-temperature gas-cooled nuclear reactor, decomposing the steam into hydrogen with a steam electrolyzer, and synthesizing methanol from this hydrogen and carbon dioxide obtained from a carbon dioxide source. The process also involves the steps of converting carbon dioxide and hydrogen into carbon monoxide and steam by carrying out a reverse shift reactor, forming hydrogen and carbon monoxide, and reacting the hydrogen and carbon monoxide into methanol in a methanol synthesis column. The process permits the use of an existing methanol production facility. The process may be modified such that the gas composed of carbon monoxide, carbon dioxide, and hydrogen is mixed with hydrogen gas generated by the steam electrolyzer, and the resulting gas is converted into methanol. Also, a power generating plant is provided in which oxygen-enriched air, generated by the steam electrolyzer using nuclear heat of the high-temperature gas-cooled nuclear reactor, is used as combustion air.

1. Field of the Invention
The present invention relates to a process for producing methanol by the use of high-temperature nuclear heat generated by a high-temperature gas-cooled nuclear reactor (HTGR for short hereinafter), and a power generating plant using high-temperature nuclear heat generated by an HTGR.
2. Description of the Prior Art
Reducing the amount of carbon dioxide (CO.sub.2) emitted by the plants of various industries is a key to solving the problem associated with global warming. Automobiles are responsible for about 20% of the total amount of carbon dioxide emitted in Japan. Therefore, it is important to reduce the amount of carbon dioxide in automotive exhaust gas. As a means to cope with this situation, methanol has attracted public attention. Methanol is a promising substitute for gasoline because it gives rise to less carbon dioxide per calorific value and a very small amount of nitrogen oxides (NO.sub.x). Methanol is conventionally produced from natural gas through its decomposition into hydrogen and carbon monoxide (CO) by the steam reforming reaction and their synthesis into methanol with the aid of a copper catalyst.
The conventional process comprises, as FIG. 5 shows, the steps of decomposing natural gas or naphtha (as the feedstock) into hydrogen (H.sub.2), carbon monoxide (CO), and carbon dioxide (CO.sub.2) by a steam reforming reaction carried out in a reformer 01, compressing these gases with a compressor 02, supplying them to a methanol synthesis tower 03, in which the reaction of CO and H.sub.2 takes place to obtain crude methanol with the aid of a copper catalyst, separating the crude methanol with a high-pressure separator 04, and refining the crude methanol in a distillation column 05.
Synthetic methanol produced by the conventional process as mentioned above does not contribute to the reduction of carbon dioxide emitted by the industry, because when such methanol is combusted it gives rise to the same amount of carbon dioxide as natural gas, so long as it is produced from natural gas.
The present invention was developed with the foregoing in mind to provide a new process for producing methanol which meets recent environmental requirements.

Method for producing methanol by use of nuclear heat and power generating plant


Novel oxy- and thio-substituted fatty acid analog substrates of myristoylating enzymes are provided which contain an oxygen or sulfur in place of a methylene group in a carbon position from 4 to 13 in the fatty acid chain of a C.sub.13 -C.sub.14 fatty acid or alkyl ester thereof.

This invention relates to novel fatty acid analog substrates of myristoylating enzymes and, more particularly, to oxy- and thio-substituted fatty acid analogs which are useful in the fatty acid acylation of peptides and proteins.
Fatty acid acylation of specific eukaryotic proteins is a well established process which can conveniently be divided into two categories. On the one hand, palmitate (C.sub.16) is linked to membrane proteins via ester or thioester linkage post-translationally, probably in the Golgi apparatus.
On the other hand, it is known that myristate (C.sub.14) becomes covalently bound to soluble and membrane proteins via amide linkage early in the protein biosynthetic pathway. In the N-myristoylated proteins, amino-terminal glycine residues are known to be the site of acylation.
A variety of viral and cellular proteins have been shown to be thus modified by the covalent attachment of myristate linked through an amide bound to glycine at their amino termini. An example of a most thoroughly studied myristoylated protein is the transforming protein of Rous sarcoma virus, p 60.sup.v-src.
The myristoylation reaction can be represented as follows: ##STR1##
Further background information on the above protein fatty acid acylation can be had by reference to the following series of articles by scientists associated with the Washington University School of Medicine:
Towler and Glaser, Biochemistry 25, 878-84 (1986); PA1 Towler and Glaser, Proc. Natl. Acad. Sci. USA 83, 2812-2816 (1986); PA1 Towler et al., Proc. Natl. Acad. Sci. USA 84, 2708-2712 (1987); PA1 Towler et al., J. Biol. Chem. 262, 1030-1036 (1987); and PA1 Towler et al., Ann. Rev. Biochem. In Press (1988). PA1 Gly-Asn-Ala-Ala-Ala-Ala-Arg-Arg and PA1 Gly-Asn-Ala-Ala-Ser-Tyr-Arg-Arg. PA1 A. 11-(Ethylthio)undecanoic acid PA1 B. 11-(Ethoxy)undecanoic acid PA1 C. 5-(Octylthio)pentanoic acid PA1 D. 11-(Methoxy)undecanoic acid PA1 E. 12-(Methoxy)dodecanoic acid PA1 F. 5-(octyloxy)pentanoic acid PA1 G. 10-(Propylthio)decanoic acid PA1 H. 10-(Propoxy)decanoic acid PA1 I. 11-(1-Butoxy)undecanoic acid PA1 J. 10-(2-Propynoxy)decanoic acid
Unique synthetic peptides having relatively short amino acid sequences which are useful as substrates of myristoylating enzymes are described in U.S. Pat. No. 4,740,588. Examples of such peptides are


A composite of an insulative layer and a fire retardant fabric which is used to make protective articles for laser surgery and which possesses favorable burning, flashing, and resistance to burn through properties. The insulative layer is preferably a hydrogel or other hydrophilic material such as a polyurethane, collagen, polyacrylonitrile, polyvinyl alcohol, or polyvinyl acetal. The fire retardant fabric is preferably a fabric woven or knitted from polyamide or polyimide fibers having a thickness sufficient to provide the desired degree of protection.

The present invention relates to articles for protection of the patient as well as surgical personnel during laser surgery. In more detail, the present invention relates to a composite for use in making articles such as gloves, surgical drapes, aprons and other items of apparel for use in protecting both patient and surgical personnel from damaged tissue resulting from direct incidence of a laser on that tissue during surgery or from fire resulting from incidence of a laser on flammable materials.
Although most damage to the skin or other tissue from a laser is repairable, the extent of the damage varies depending upon the degree of absorption of the laser wavelength and the duration of exposure such that there is potential for serious damage. Adding to that potential is the fact that reflection of the laser beam is potentially as damaging as direct contact with the beam. Various safety measures are employed depending upon the surgical procedure to protect against such damage. For instance, a back drop is used behind the tissue being lased, when possible, and in the abdominal cavity, a wet wooden tongue blade, titanium rod or wet laparotomy sponge can be used to protect underlying tissue. Abdominal and cranial cavities are filled with sterile saline to absorb the energy of the beam. Non-involved, exposed tissue is covered with wet laparotomy sponges, four by fours, or cottonoids. Patients are restrained from movement, and beaded or other non-reflective instruments are used.
Fires can occur by ignition of a drape, endotracheal tube, or article of clothing, plastic, or rubber in the treatment area. On information and belief, none of the standard surgical drapes will resist impact from a laser beam, Precautions against fire include, for instance, the covering of surgical drapes with wet towels and/or laparotomy sponges, the wetting of all the drapes, sponges and gauzes used in the area of laser application, and the precautions listed above for protecting against laser burns.
The protection provided by even the most careful application of all of these precautions simply is not sufficient. Depending upon the wavelength, time of exposure, type of laser and several other factors, the laser is capable of vaporizing these "protective" articles in exactly the same manner as the tissue on which the laser is intended to be used. There is, therefore, a need for effective protective articles for use in the treatment area.
At least one attempt has been made to provide such an article. U.S. Pat. No. 4,601,286 is directed to an "Article for the Protection of Living Tissues", said to protect ". . . living tissue from damage due to exposure to lasers . . . ". That patent describes the use of a hydrogel in the form of a drape or dressing having an opening through which the laser light can pass to impinge on the portion of the tissue to be lased, the opening having a size and shape approximating that of the tissue site to be lased (col. 5, lines 13-20, 56-60). In practice, however, such an article does not protect against laser burns; at best, such articles may provide some protection against ignition because of the high water content of the hydrogel. Experimentation has shown that penetration of a twenty-five watt or greater laser through such articles is instantaneous; further, the hydrogels are clear, making them of limited use for argon lasers which "seek" color. Penetration of the laser through the hydrogel does not appear to depend on the thickness of the hydrogel--instead, the laser penetrates instantaneously no matter what the thickness. There is, therefore, still a need for a material from which effective protective articles can be made for use in laser surgery.

Protective articles for use in laser surgery


A super-conducting electro-magnet for use in an MRI system comprising a helium vessel within which magnet windings are positioned, a vacuum chamber within which the helium vessel is contained, at least one thermal shield positioned between the helium vessel and the vacuum chamber in spaced apart relationship, a service turret including a refrigerator thermally coupled to the said at least one shield for cooling purposes, a tube which extends through the turret from the windings to facilitate filling, and conductors which extend through the turret from the windings to facilitate current injection to the windings and to provide a vent for the helium gas.

This invention relates to super-conducting electro-magnets for use in magnetic resonance imaging (MRI) apparatus.
Super-conducting electro-magnets for MRI apparatus comprise windings immersed in liquid helium so that they are cooled to temperatures of about 4.degree. K at which they become super-conductors. A helium vessel containing the windings is positioned within a vacuum chamber which serves to reduce heat gain by convection and in order to reduce heat gain by radiation, thermal shields are positioned between the helium vessel and the vacuum chamber. The thermal shields, are usually cooled by a refrigerator which in known apparatus is provided in a refrigerator turret. Such an arrangement is described in European patent specification EP0260036. The refrigerator turret extends into the vacuum chamber to facilitate thermal coupling of the shields to the refrigerator. In order to provide access to the windings for current injection purposes, and access to the helium vessel for filling and topping up purposes, in known apparatus a service turret is additionally provided.
Although generally satisfactory in operation, this known arrangement has the disadvantage that it tends to be expensive to fabricate and time consuming to assemble. It also has the disadvantage that a current probe must be inserted to make electrical contact with a connector in the helium vessel when it is desired to inject current into the windings. The insertion of the current probe is an undesirable operation because the turret must be opened to atmosphere, and air/water vapour from the atmosphere could enter the turret where it would freeze on the cold surfaces, creating a blockage. In addition, inserting the current probe into a magnet which is energised can cause the magnet to quench if insufficient care is taken to cool the probe fully before engagement with the connector on the windings. Magnets with the known service turret may be fitted with permanently connected current leads, but because these are cooled only by gas boiling off from the helium vessel, they impose a considerable heat load onto the helium vessel by virtue of having to have good electrical conductivity (and therefore good thermal conductivity) to connect electrical current to the windings. The reasons for this are well understood by those skilled in the art, and further detailed explanation is therefore believed to be unnecessary.


A steam supply apparatus (1) for enhanced oil recovery from an oil field (10). The steam supply apparatus includes a water circulating portion (50) providing a continuous flow of water to a water heater (4) for the production of a mixture of steam and water, and a separator (5) for directing the steam to the oil field. Water returned from the oil field is purified in a water treatment apparatus (3) to provide make-up water to the water circulating portion. A buffer volume (3b) is provided in fluid communication between the water treatment apparatus and the water circulating portion. The buffer is sized to provide a time lag between a degradation of the quality of the purified water and an occurrence of an unacceptable scale production in the water heater, thereby allowing continued safe system operation until the water quality problem is corrected.

Various enhanced oil recovery techniques are known for increasing the production of heavy crude oil, including gas injection, chemical injection, microbial injection and thermal recovery. Thermal recovery methods involve the introduction of a heated fluid, such as steam, into an oil field in order to decrease the viscosity of the oil and thus to facilitate its removal.
U.S. Pat. No. 5,058,675 discloses a method and apparatus for the extraction of oil and gas from oil shale wherein solar-heated steam is injected into a well in an open system wherein there is no water recovery from the well. Such systems consume a large quantity of water and are not practical for all applications.
The recovery and reuse of water for a steam injection enhanced oil recovery system requires the removal of minerals from the recovered water prior to reuse as feed water for a boiler, since such minerals will concentrate in the boiler and cause an unacceptable scale buildup which inhibits heat transfer and necessitates periodic cleaning operations. U.S. Pat. No. 8,167,041 discloses a method for the recovery of hydrocarbon from oil sands which avoids such scaling problems. A solar thermal power plant is used to generate steam. The steam in injected via an injection well into a formation in the ground to extract bitumen at an oil producing well. FIG. 7 of that patent shows a solar heating system which has a first closed circuit of a heat transfer fluid. A heat exchange unit (steam generator) is provided to exchange heat from the heat transfer fluid to a water steam mixture in a second circuit. Steam is produced in the second circuit which is injected into the ground formation via the injection well. Produced water from the formation is separated from the extracted oil and recirculated in the second circuit. The first circuit utilizes a clean heat transfer fluid, which may be clean water, to prevent scaling of the solar collection panels. The second circuit uses a relatively dirty water steam mixture. The water returned from the formation includes oil residuals and minerals which would cause scaling of the heat transfer surfaces of the solar collector if this dirty water were directly supplied to the solar field.


The present disclosure provides a voice signaling transmission method and device. The voice signaling transmission method includes: sending, by a second device, a request signaling to a first device; receiving, by the second device, a signaling for requesting the second device to try a call sent by the first device, and sending a signaling for trying a call to the first device; receiving, by the second device, a ringing signaling sent by the first device and sending a temporary response signaling to the first device; and receiving, by the second device, a signaling for confirming the response and a signaling for confirming the request which are sent by the first device and sending a response signaling to the first device.

In mobile communication, a voice call flow is complex, and a voice signaling volume is too large. It is easy to generate a problem that voice signaling cannot be effectively transmitted when environment of a channel for transmitting signaling is complex. For example, in satellite communication, environment of an air interface is complex, and if a standard Session Initiation Protocol (SIP) is adopted, it is easy to generate problems that voice signaling cannot be reliably transmitted and a success rate of voice telephone service is low.
Therefore, a new technical solution for transmitting voice signaling is needed to ensure the reliability of voice information transmission.

Voice signaling transmission method and device


A pair of optical profile measuring systems 10, 20 are provided at positions faced to both sides of a wafer 1 vertically supported at its edge. Each system 10, 20 includes a light emitter 11, 21 for discharging a measuring light beam 12, 22, a collimator lens 14, 24 for rectifying the light beam 12, 22 into a collimated beam, an optical flat 15, 25 for transmitting the collimated light beam 12, 22, a light detector 16, 26 receiving the light beams 12, 22 reflected on a surface of the wafer 1 and on a referential plane of the optical flat 15, 25 through the collimator lens 14, 24 and a computer 17, 27 for processing interference fringes which occur between the surface of the wafer 1 and the referential plane of the optical flat 15, 25. Profiles of main and back surfaces of the wafer as well as its thickness variation are easily measured utilizing light interference fringes corresponding to both sides of a wafer.

The present invention relates to an optical apparatus which enables high-speed measurement of profiles of both sides as well as a thickness variation of a wafer.
A thickness variation of a wafer has been measured so far by either an optical method using interference fringes or a physical method using displacement sensors for scanning both sides of the wafer. The term thickness variation in this specification means a thickness distribution calculated as a distribution in height of one surface from the other surface of the wafer which is regarded as an ideal flat plane.
In the conventional optical method, thickness variation is calculated from interference fringes which occur between a referential plane of an optical lens and a surface of a wafer. The method enables high-speed measurement, but uses a vacuum chuck for holding the wafer. When the wafer is fixed to the vacuum chuck, its backside attracted to the vacuum chuck is likely deformed. Deformation of the wafer at the backside may be incorporated as an error in measurement results, so that the thickness variation of the wafer can not be obtained with high accuracy. There is also a defect that chucking flaws are likely formed on the backside, since the wafer is held in direct contact with the vacuum chuck.
Use of interference fringes derived from light beams reflected on both sides of a wafer is for detecting a thickness variation of a wafer is disclosed in Japanese Patent Application Laid-Open 1-143906. In this method, light beams discharged from a light source are split to transmitting and reflecting beams by a beam splitter, reflected on both sides of a wafer and then inputted to light detectors. Optical interference fringes occur in correspondence with a difference in an optical path between the transmitting and reflecting beams.
On the other hand, in the physical method using displacement sensors, a deviation in thickness of a wafer is calculated on the basis of signals detected by capacitance type displacement sensors provided at both sides of the wafer, to detect a thickness variation of the wafer regarding a back side as an ideal flat plane. For instance, Japanese Patent Publication No. 5-77179 discloses provision of displacement sensors faced to both sides of a wafer for production of deviation signals from every part of the wafer being rotated.
The physical method using displacement sensors has been commonly used so far for detecting a thickness variation of a wafer, since measurement is performed with high reproductivity without any defects caused by a vacuum chuck. However, the wafer necessarily rotated for scanning due to a small probe of the displacement sensor, so that it takes a therefor long time to scan the whole surface of the wafer.
When a part of the wafer attracted to a vacuum chuck is scanned, the wafer is re-held, and then movement of the sensors is changed to a swinging mode for scanning the part which was attracted with the vacuum chuck, as disclosed in Japanese Patent Publication No. 5-77179. The re-holding prolongs a measuring time in total and needs troublesome works.
During measuring, the wafer is rotated. Due to rotation, both sides of the wafer come in contact with a large quantity of the air, so that the wafer is exposed to adhesion of particles suspended in the air. Particles are also transferred from the vacuum chuck to the backside of the wafer. Adhesion of particles often unfavorably affects therefor the measurement results.
When a wafer is scanned with displacement sensors, an outer part of the wafer is not subjected to scanning in order to avoid incorporation of edge effects into detected signals. That is, the outer part of the wafer is treated as an unmeasurable zone, resulting in reduction of a surface part which can be measured.
A wafer for measurement is held by attracting its backside center to a vacuum chuck. Due to this holding means, measurement results are likely affected by gravity as enlargement of the wafer in size. Deformation of the wafer at its periphery is often incorporated as an error into measurement results.
Defects caused by holding a wafer with a vacuum chuck is eliminated by an optical method of measuring a thickness variation of a wafer in such a state kept free from a holding force, as disclosed in Japanese Patent Application Laid-Open 1-143906. According to this method, measurement is performed with ease in a short time, since the thickness variation is calculated from interference fringes. However, the interference fringes which occur between transmitted and reflected light beams reflected on both sides of the wafer are used for calculation of the thickness variation. Consequently, the thickness variation is merely judged from the interference fringes, but undulation or inclination of the wafer which is not accompanied with a thickness deviation can not be detected. In addition, affections of particles floating in the air, positioning of a wafer, dimensional accuracy of various parts to a measuring apparatus, etc. are likely incorporated as errors into measurement results due to a long light path necessarily designed for occurrence of interference fringes.

Optical apparatus for measuring profiles of a wafer

Super Silicon Crystal Research Institute Corporation


A semiconductor memory device includes a die having a semiconductor memory circuit formed thereon and a plurality of pads at the periphery of the die that are electrically coupled to the circuit. Electrically conductive leads have a pin end for external coupling, and a free end electrically connected by bond wires to certain pads on the die. An encapsulating material such as epoxy encapsulates the die, bond wires and free ends of the leads to form a packaged chip. A superfluous lead such as an address lead unused during testing, redundant voltage supply lead or non-connected lead is coupled, by means of a bond wire, to a pad that, in turn, is coupled through a switching transistor to a common cell plate or DVC2 node for all storage capacitors in the memory circuit. External power can thereby be provided to the DVC2 node to simultaneously apply a high voltage to this node of all capacitors during stress testing of the chip. The arrangement allows for efficient testing for dielectric defects in the capacitors while the die is in packaged chip form.

Various types of defects and failures can occur during the manufacture of semiconductor devices. A "failure" occurs when a semiconductor device fails to meet its specifications. A "defect" occurs when a semiconductor device has an improper circuit structure that currently presents a failure of the device, or has the potential to fail during the expected lifetime of the device. For example, due to a manufacturing error, an insulator or dielectric such as nitrite between electrodes in a capacitor can be thinned or include pin holes which could currently provide a short or decreased capacitance therebetween, or could break down over a period of time ("a dielectric defect"). After this period of time, typically during prolonged use of the device, the thinned or apertured dielectric provides a conductive path between the electrodes so that a "high" voltage stored on one electrode forces a "low" voltage on the adjacent electrode to rise to a high value, resulting in a failure of the device.
Therefore, an aperture between electrodes that presently reduces the capacitor's ability to hold a charge is a defect resulting in a failure of the semiconductor device. An apertured or thinned dielectric that has not yet formed a sufficient short between the two electrodes, however, is a defect that has not yet evidenced itself as a failure. As a result, the semiconductor device can be operated for a brief time under standard operating conditions and voltages before the defect manifests itself as a failure.
Testing is performed on semiconductor devices to locate defects and failures in such devices. As circuit density on semiconductor devices increases, the number of defects and failures can increase. Semiconductor manufacturers, therefore, have an increasing need to detect for defects and failures in semiconductor devices as circuit density on these devices increases.
Thus, for quality control and to improve yields of acceptably operable semiconductor devices, semiconductor devices are tested, often before a die containing the semiconductor device is packaged into a chip. A series of probes on a test station electrically contact pads on each die in a wafer to thereby access portions of the individual semiconductor devices on the die. For example, in a semiconductor memory device, the probes contact address and data input/output pads to access selected memory cells in the memory device. Typical dynamic random access memory devices ("DRAM") include one or more arrays of memory cells that are each arranged in rows and columns. Each array of memory cells includes word or row lines that select memory cells along a selected row, and bit, digit or column lines (or pairs of lines) that select individual memory cells along a row to read data from, or write data to, the cells in the selected row.
During testing, predetermined data or voltage values are typically written to selected row addresses, or row and column addresses, that correspond to certain memory cells, and then the voltage values are read from those memory cells to determine if the read data matches the data written to those addresses. If the read data does not match the written data, then the memory cells at the selected addresses likely contain defects and the semiconductor devices fail the test.
A person testing the several dies on the wafer can then examine a particular die itself, by means of a microscope, to determine if failures occurred from masking defects, during the deposition of certain layers, and so forth. During the initial development of a semiconductor device, and while the device is in die form, changes to masks can be made to compensate for most detected failures. However, once a semiconductor device is in production and packaged as a chip, redundant circuitry on the semiconductor device can be employed to compensate for only certain detected failures. Redundant circuitry on the semiconductor device cannot compensate for many detected failures, and therefore, such failed devices must generally be discarded.
To increase output of acceptable semiconductor devices, semiconductor manufacturers strive to perform rapid testing of the semiconductor devices to expose defects in the devices before shipping them to a vendor or user. A semiconductor device can be most thoroughly tested when the device is still in die form on the semiconductor wafer. Semiconductor wafers, however, are often difficult to manipulate, and typically require a test bed or other apparatus to releasably secure the wafer while the probes are adjusted to contact the pads on each die on the wafer. As a result, testing of semiconductor devices in die form is time consuming. Therefore, semiconductor manufacturers desire to test a given semiconductor device after it has been packaged as a semiconductor chip, because the chip can be automatically inserted into a test socket for testing using pick and place machinery. Automated testing circuitry can then apply predetermined voltages and signals to the chip, write test patterns thereto, and analyze the results therefrom to detect for failures in the chip.
Often, the number of pads on a die is greater than the number of pins on the packaged semiconductor chip. Therefore, as noted above, certain tests performed while the semiconductor device is in die form cannot be performed on the device after it has been packaged. As a result, package chips necessarily undergo less rigorous testing than unpackaged dies. Packaged chips can include manufacturing defects that are not yet failures and thus are undetectable by the limited number of tests capable of being performed on the packaged chips.
For example, in typical semiconductor memory devices, such as DRAMs, the capacitor in each memory cell has a "storage electrode" that stores a voltage value representing the data written to the memory cell (a high voltage value indicating a logical "1" value and a low voltage value indicating a logical "0" value). "Ground" electrodes for each of the capacitors are typically electrically intercoupled at a "DVC2 node" as a single conductive layer in the semiconductor device to form a "cell plate." The DVC2 node is typically maintained at a voltage value approximately half that of the positive supply voltage or Vcc/2 to thereby provide a maximum voltage differential between the storage and cell plates of each capacitor, regardless of whether a high or low voltage is written to the storage plate.
To test for the dielectric defect discussed above, a test circuit writes low voltage values (as logical "0" values) to all capacitors in the memory cells of the memory cell array. The test circuit thereafter raises the voltage at the DVC2 node to a voltage value approximately equal to Vcc. The test circuit then determines whether all the memory cells have maintained a logical "0"value. If not, then the "high" voltage value applied to the DVC2 node has leaked or shorted to the storage plate of a capacitor in a memory cell, causing the low voltage or logical "0" value initially stored thereon to rise and become a high voltage or logical "1" value.
The time required for the high voltage value on the DVC2 node to raise the voltage on the storage plate of a capacitor will vary depending upon the severity of the defect in the dielectric between the cell and storage plates. As a result, a high voltage value over a continuous period of time must be applied to the DVC2 node to force the failure in one or more of the memory cells in the semiconductor device. External test circuitry typically must apply such a continuous, high voltage value to the semiconductor memory device while the device is still in its die form.
Many semiconductor memory devices include an on-chip voltage pump that provides the Vcc/2 voltage to the DVC2 node. The on-chip voltage pump, however, typically does not have the capacity to raise the voltage of the DVC2 node well beyond the Vcc/2 value for a prolonged period of time. Consequently, dielectric defects cannot be efficiently tested in packaged chips. As a result, dielectric defects can typically only be tested efficiently when the semiconductor memory device is in die form. Probes access the DVC2 node and apply supplemental power to the device being tested to thereby provide the high voltage value to the cell plate over the continuous test period. Such a dielectric stress test, however, suffers from the above-described difficulties in testing semiconductor memory circuits when in die form. Therefore, while such a test is desirable, its value is offset by the time consuming process of manipulating and testing semiconductor wafers.

Method and apparatus for testing of dielectric defects in a packaged semiconductor memory device


Methods are described for treating a whey protein mixture to increase a relative concentration of α-lactalbumin protein in the mixture. The methods may include the step of adjusting a temperature of the whey protein mixture to about 10° C. or less, and adjusting the pH of the mixture to greater than 7. The may further include adding a protease enzyme to the whey protein mixture that selectively hydrolyzes β-lactoglobulin protein in the mixture. The activity of the protease enzyme in the hydrolyzed whey protein mixture may be terminated before a substantial portion of the α-lactalbumin protein has been hydrolyzed by the enzyme. In some instances, the whey protein mixture may also include glycomacropeptides that are selectively hydrolyzed with the β-lactoglobulin protein. The β-lactoglobulin and glycomacropeptide hydrolysates may be separated to produce an enhanced α-lactalbumin protein composition for infant formula, among other products.

Whey is a liquid by-product of cheesemaking processes that provides a source of high quality protein for foods, cosmetics, and other products. Whey protein from cow's milk is actually a collection of different proteins that primarily include β-lactoglobulin (β-Lg), and α-lactalbumin (α-La), as well as glycomacropepties (GMPs) cleaved from the native casein proteins in the milk that coagulate into the cheese curd. While β-Lg has the greatest wt. % in cow's milk, this protein has a much lower concentration or is absent in human milk and can be more difficult to digest than α-La. Efforts have been made to reduce the high concentration of β-Lg in whey protein from cow's milk and bring the relative concentration of β-Lg to α-La closer to that of human milk.
These efforts have included contacting the whey protein with resins that selectively absorb or attach one or more of the whey proteins. These separation processes may include passing the native whey protein over a column of resin beads that selectively capture one or more of the protein components in the whey. Unfortunately, there have been significant challenges in developing resin materials that selectively bind α-La or β-Lg that do not capture significant amounts of the other. There have also been challenges releasing the bound proteins from the resin once the whey has passed through the column. Processes and resins have also been developed for the selective binding of GMPs, but these resins do not substantially alter the relative concentration of β-Lg to α-La, which is still heavily tilted towards β-Lg in bovine whey.
Additional efforts to separate and purify native whey include the addition of one or more chemical elements to whey that selective precipitate one or more of the proteins. Examples of these processes include the addition of ferric chloride to the whey under tightly controlled temperature and pH conditions to precipitate β-Lg. Like the resin separation techniques, there have been problems selectively precipitating the β-Lg without also precipitating significant amounts of α-La. Furthermore, removal of the precipitation salts on a commercial scale adversely impacts the economics of purifying bovine whey that is intended for human consumption.
Still other approaches have used targeted enzymatic hydrolysis to denature one or more of the whey proteins. There remains significant unpredictability in the selection of—among other factors—the enzymes, temperature, reaction time, and acidity when targeting a specific whey protein for hydrolysis without also hydrolyzing significant amounts of other proteins. In addition, small protein hydrolysates made of just one or a few amino acids (i.e., oligopeptides) often create bitter flavors and brothy solutions that have a very disagreeable taste for the average consumer.
There remains a need for processes and systems that can increase the concentration of α-La from sources of native whey such as cow's milk and sweet whey. There also remains a need for purified whey compositions with increased concentrations of α-La and reduced concentrations of β-Lg and/or GMPs that can be produced economically on a commercial scale and that are palatable to most consumers. These and other challenges are address in the present application.

Alpha-lactalbumin enriched whey protein compositions and methods of making and using them


The invention provides a roof reinforcement member including an extruded aluminum alloy part which is upwardly convex and extends in a vehicle lateral direction. The extruded aluminum alloy part includes a pair of upper and lower flanges approximately parallel-facing each other as seen in a cross-section thereof and a pair of webs formed to stand along the vehicle height direction. The pair of flanges and the pair of webs form a closed sectional part. The pair of flanges each have a projecting flange portion. In the cross-section, the lower flange is thicker than the upper flange and/or the lower flange is wider than the upper flange, and the neutral axis of upward/downward bending is positioned lower than the middle of the height of the cross-section. This arrangement can reduce the stress generated on the lower side of the cross-section when the extruded aluminum alloy part is bent, so that the extruded aluminum alloy part can be effectively made stronger against deformation.

The present invention relates to an automobile roof reinforcement member extending in the vehicle lateral direction under an automobile roof panel and, more particularly, to an automobile roof reinforcement member made of extruded aluminum alloy highly deformation resistant under an axial compressive load (applied in the longitudinal direction of the roof reinforcement member).
An automobile roof reinforcement member (hereinafter also referred to simply as a "roof reinforcement member) is installed in proximity to a roof panel member of an automobile such that it extends in the vehicle lateral direction with each end portion thereof in the vehicle lateral direction joined to a frame part, for example, a body side panel or a center pillar included in the corresponding side of the vehicle body either directly or via a bracket provided in the end portion. This is to secure rigidity and strength in the vehicle lateral direction of the roof reinforcement member and also to secure dent resistance and tensile rigidity of the roof panel member.
With the side crash standard for vehicles intensified in recent years, automobile roof reinforcement members have come to be required to have high strength against deformation caused by a compressive load applied, from a vehicle side, in the vehicle lateral direction. What is generally done to enhance the strength against axial compression of a roof reinforcement member is to form a closed sectional part in the roof reinforcement member. Aluminum alloy for extrusion is suitable for forming a shape having a closed sectional part while also being suitable to form light-weight items. Hence, various cross-sectional shapes having a closed sectional part of roof reinforcement members have been proposed (refer to, for example, Japanese Patent Laid Open Nos. 2003-112656, 2006-240420, and 2006-240543).
As stated in Japanese Patent Laid Open No. 2006-240543, the strength against axial compression of a roof reinforcement member is defined by the axial compressive load that causes the roof reinforcement member subjected to the load to start bending upward or downward. Namely, to increase the strength against deformation caused by axial compression of a roof reinforcement member, it is most effective to increase the strength against upward/downward bending of the roof reinforcement member.
As shown in FIG. 8, an extruded aluminum alloy part disclosed in Japanese Patent Laid Open No. 2006-240543 includes, as seen in a cross-section thereof perpendicular to the direction in which the aluminum alloy part was extruded, a pair of upper and lower flanges 1 and 2 approximately parallel-facing each other and a pair of webs 3 and 4 formed approximately perpendicularly to the flanges 1 and 2. The flanges 1 and 2 and webs 3 and 4 form an approximately rectangular closed sectional part 5. The flanges 1 and 2 each project, in the vehicle longitudinal direction, forward and rearward from the closed sectional part 5 thereby forming projecting flange portions 1a, 1b, 2a, and 2b, respectively. The extruded aluminum alloy part having the above described cross-sectional shape, i.e. including the flanges 1 and 2 with portions projecting from the closed sectional part 5, has higher strength against upward/downward bending than an extruded aluminum alloy part having a closed sectional part only without any projecting portion, provided that the two extruded aluminum alloy parts have an equal cross-sectional area (refer to paragraph 0025 of Japanese Patent Laid Open No. 2006-240543).


An apparatus and method are provided for identifying a call record of a telephone call to be overflowed from a source automatic call distributor to a destination automatic call distributor. The call record is of a type having been previously stored under a call identifier of the source automatic call distributor in a memory of the host computer serving both the source automatic call distributor and destination automatic call distributor in an area of the memory reserved for the source automatic call distributor. The method includes the step of storing a call action provided message in a call overflow table of the host computer including the call identifier of the telephone call and an identifier of the source automatic call distributor. The method further includes the step of transferring an overflow request to the destination automatic call distributor including the call identifier and searching the overflow table using the call identifier transferred to the destination automatic call distributor to locate the identifier of the source automatic call distributor. Finally, the method includes the step of locating the call record using the call identifier and located identifier of the source automatic call distributor.

Automatic call distribution systems are known. Such systems are typically used in an organizational context within private branch telephone exchanges (PBXs)as a means of distributing telephone calls among a group of agents of the organization. While the automatic call distributor (ACD) may be a separate part of the PBX, often the ACD is integrated into and is an indistinguishable part of the PBX.
Often the organization disseminates a single telephone number to its customers and to the public in general as a means of contacting the organization. As calls are directed to the organization from the public switched telephone network (PSTN), the automatic call distribution system directs the calls to its agents based upon some algorithm, typically based upon availability. For example, where all agents are consider equal, the ACD may distribute the calls based upon which agent position (telephone) has been idle the longest.
In order to distribute incoming calls from the PSTN to the available agents, the interaction of a controlling computer with a switching fabric of the PBX and ACD becomes essential. Often a connection to a local PSTN is in the form of a number of trunk connections. Each of the trunk connections is monitored by the controller for incoming calls. Where a call is detected, the controller searches for and selects an idle agent. Upon selecting an agent, the controller commands the switch to form a connection between the incoming trunk and selected agent.
In more complicated systems, the organization may use a number of telephone numbers to identify different individuals and functions within the organization. Each telephone number may be assigned to a particular incoming trunk or group of incoming trunk lines. As such, the controller may be required to recognize a call target based upon an identity of an incoming trunk line and route the call accordingly.
In other systems, the ACD of an organization may receive calls directed to different call targets over the same trunk lines. In such a case, the call target may be identified to the ACD by a pulse code modulated (PCM) signal transferred from the PSTN to the controller of the ACD by a dialed number identification service (DNIS) operating from within the PSTN.
In systems associated with service organizations, where many calls are received and handled by many agents, it may be important for an agent to have ready access to customer files. In such a situation, a database is maintained of existing customers. Customer records may be displayed on agent terminals as the agents converse with specific customers. In some cases, the customer may be identified to the database for display of records on the terminal by the agent entering a customer identifier into a keyboard associated with the terminal. Alternatively, the controller of the ACD may transfer an identifier of the customer to the database based upon an automatic number identification (ANI) facility, operating from within the PSTN.
Where ANI is used, the controller of the ACD receives the ANI digits (identifying the caller via the caller's telephone number) at the same time the call arrives from the PSTN. Upon selecting an agent, the controller may transfer a call to a queue for the selected agent or directly to the selected agent. At the same time that the call is delivered to the agent, the controller sends an identifier of the selected agent and ANI number of the customer to a controller of the database (the host). The host, in turn, displays the customer records via a computer monitor of the selected agent at the same time the call is delivered.
As a further feature, calls may be transferred among agents. Where a first agent finds that he or she cannot help a particular customer, the agent may activate a key on a keyboard of the agent and may enter an identity of another agent or agent group that may be better able to help the customer. The controller of the ACD may immediately connect the call to the newly identified agent, or may place the call in a queue until the identified agent becomes available.
In either case, the controller transfers a message to the host identifying the previous and newly identified agent. Since the host knows the identity of the customer displayed at the terminal of the previous agent, the host may now display those same customer records at the terminal of the newly selected agent.
Where a call is placed in a queue, the ACD controller may monitor a total time that the call has been in the queue. Where the time exceeds a threshold value, the controller may transfer (overflow) the call to a newly selected agent at another less heavily loaded ACD (overflow ACD) within the same organization. The controller of the transferring ACD transfers DNIS and ANI information as well as a call sequence number assigned by the transferring ACD to the overflow ACD. The overflow ACD, upon receiving the call, transfers the information to the host including an identifier that the call is an overflow call. The host in turn then polls each ACD to identify the transferring ACD and any newly created call records created by the transferring ACD.
While the existing method of ACD operation is relatively satisfactory, it is dependent upon a record of connection transactions as a method of identifying a call to the host. Where a connection to an agent is completed, a transaction identifier is sent to the host memorializing the transaction. The record of the connection is placed in a call record held in an area reserved for the transferring ACD. Where a call is received and placed in a queue for delivery to the next available agent, a call arrival message is sent to the host and saved in the transferring ACD's record area. Where the call is then transferred to another ACD, there is no means for directly identifying the transferring ACD and the host must poll each ACD to identify the call record of the call. Accordingly, a need exists for a better method of tracking overflow calls among ACDs.

Apparatus and method for identifying records of overflowed ACD calls


The present invention describes a process for pretreatment of lignocellulosic biomass that comprises the step of contacting a lignocellulosic biomass with an ionic liquid consisting of a phthalic salt of dicholine in the weight ratio from 1:1 to 1:100 of biomass:ionic liquid, said step taking place for a period of time that varies from 0.4 to 48 hours and in a temperature range that varies from 60 to 200° C. Furthermore, the present invention also relates to the use of the pretreated lignocellulosic biomass in an enzymatic hydrolysis process.

In the search for sustainable alternatives to replace petroleum derivatives, the use of lignocellulosic biomass as a raw material or energy source is an attractive resource owing to its great availability and its low cost.
The lignocellulosic materials may be waste products, such as sugar cane bagasse and maize straw; hardwood, such as aspen and poplar; coniferous wood, such as pine and fir; cellulosic wastes, such as recycled paper pulp and newsprint; herbaceous biomass, such as alfalfa hay and reed canary grass; municipal solid waste; among others.
By fermentation of the sugars derived from this type of biomass, for example, it is possible to release a wide range of bioproducts, such as ethanol, succinic acid, lactic acid, 2,3-butanediol, citric acid, acetic acid, itaconic acid, fumaric acid, n-butanol, among others.
However, the chemical composition of the lignocellulosic materials makes it difficult to produce these derivatives directly by fermentation, since they are polymers of complex carbohydrates basically consisting of cellulose (C6H10O5)x, hemicellulose (C5H8O4)m and lignin (C9H10O3(OCH3))n.
To facilitate access to the carbohydrates in the biomass for biological conversion, thus maximizing fermentation of the sugars, it is necessary to apply some pretreatment on the biomass for solubilization and separation of one or more of its components, especially lignin.
The pretreatment of the biomass has the following objectives: to reduce the degree of polymerization of the cellulose molecules, to make them accessible for the hydrolysis process, to avoid the formation of byproducts that are inhibitors of the processes of hydrolysis and fermentation, and primarily, to be economically viable.
At present there are various methods of pretreatment, which may be physical, chemical or physicochemical.
The chemical pretreatments may employ organic or inorganic compounds, normally employing acids, bases or organic solvents.
Ionic liquids also represent a promising alternative as solvents in the chemical pretreatment of biomass.
Brandt et al., in "Deconstruction of lignocellulosic biomass with ionic liquids"—Green Chem., 2013, 15, 550-583, describe a biomass pretreatment that uses ionic liquids as solvents. The ionic liquids described comprise cations selected from imidazoles, pyridine, piperidine, pyrrolidine, ammonium, sulfonic and phosphonium, and anions selected from sulfates, sulfonates, bromides, chlorides, iodides, acetates, phosphates and cyanamides.
The investigation by Perez-Pimienta et al., in "Comparison of the impact of ionic liquid pretreatment on recalcitrance of agave bagasse and switchgrass"—Bioresource Technology 127 (2013) 18-24, also describes ionic liquids as being excellent solvents for the pretreatment of lignocellulosic biomass. The ionic liquid assessed in this work was 1-ethyl-3-methyl imidazole acetate in various concentrations.
However, solvents based on imidazoles present risks with respect to the operational safety of the reaction, besides having the disadvantage of the occurrence of parallel reactions of degradation, both in laboratory processes and in industrial processes.
Therefore an aim of the present invention is to provide an alternative chemical pretreatment of lignocellulosic biomass that does not have the drawbacks identified in the prior art.

Method for pretreating lignocellulosic biomass


An image record apparatus for recording a visible image on each of image record media 14 has a light application section 30 for applying exposure light to the plurality of placed image record media 14, a voltage application section 20 for applying an image write voltage to each of the plurality of placed image record media 14, and a control section 40 for controlling the light application section 30 and the voltage application section 20 so that exposure light for representing a visible image is applied to the plurality of placed image record media and the image write voltage is applied to the image record medium 14 on which the same visible image as the image is to be recorded.

1. Field of the Invention
This invention relates to an image record apparatus for copying information from a display used with an office automation (OA) machine, an information communication terminal, a POS terminal, etc. and a record medium such as paper, an image record method used with the image record apparatus, an image record medium holder, and an image record medium onto which information is written.
2. Description of the Related Art
Hitherto, a display panel formed using a plastic film substrate of a polymer film, etc., has fully showed as a display, etc., of a hand-held electronic machine, the advantages that the display panel is thin and lightweight and can be bent in comparison with a display panel formed using a glass substrate.
Most of all, attention is focused on a liquid crystal display device using a composite of self-hold liquid crystal comprising a cholesteric liquid crystal dispersed in a transparent resin material and a resin because the liquid crystal display device has a stable memory property and can produce high-definition display by simple matrix drive without the need for an active drive circuit required for TFT liquid crystal, etc.
Particularly, the liquid crystal display device provided by making use of a light dispersion mode of a cholesteric liquid crystal capable of providing a high reflection contrast in a light reception type display to provide compatibility between high-speed display and high resolution is free of flicker and thus produces easy-to-see display and makes user's eyes hard to get tired, so that it satisfies the need for being easy on eyes of human beings. In addition, it can memorize the display contents and moreover can display and store information with no power supply and thus also satisfies the need for energy conservation and being friendly to the environment.
Further, a system wherein a composite of self-hold liquid crystal and a resin and a photoconductor are combined into an image record medium and a voltage is applied to the image record medium and exposure light is also applied for displaying a visible image is predominant as a printer, etc., using an image record medium in place of paper and is also predominant as a tool for innovating the former mode in which a hardcopy of information displayed on an electronic display is made before the information is read, and can also realize resource savings and waste reduction by making the most of the feature of being reusable.
Assuming that the user sees the image record medium using liquid crystal with the medium picked up like paper and carries the image record medium with the hand, it is considered that if a record apparatus for applying a voltage to the image record medium and applying exposure light to the image record medium to write information and the image record medium are made separatable for use, the convenience is enhanced.
However, if the image record medium and the record apparatus are separated, the image record medium holds only the currently recorded information like a paper medium and full use of the feature of being repeatedly rewritable is not made.
On the other hand, the record apparatus for applying exposure light while applying a voltage requires both a light emission section for applying exposure light to an image displayed on an image display body including a luminous, electronic display for displaying image information or on a translucent material from behind and a voltage application section for applying a voltage to an image record medium and thus it is not easy to configure the record apparatus as a portable type.
JP-A-Hei. 11-237644 discloses a method of sequentially exposing while moving a laser beam and a light emitting diode array to miniaturize an image record apparatus of an image record medium.
According to the method, it is not necessary to expose the full face of an image record medium at a time and thus the light application section can be miniaturized, thereby miniaturizing the whole image record apparatus.
In this disclosed method, however, writing image information to an image record medium is slowed down and thus the need for displaying image information at high speed cannot be satisfied; this is a problem.
To rewrite new image information onto an image record medium separated from the image record apparatus, the user involves a burdensome procedure of bringing the image record medium into a location where the image record apparatus is placed, setting the image record medium in the image record apparatus, and exposing while applying a voltage. Further, to record the same or different image information on a plurality of image record media and distribute the image record media to a plurality of persons or locations, the burdensome procedure of setting one image record medium at a time in the image record apparatus and applying a voltage to each image record medium and exposing it is also involved. It is considered that the burdensome step of setting an image record medium in the image record apparatus is not eliminated if the image record apparatus is miniaturized to a portable size. To stack a plurality of image record media on each other and expose the image record media from the same light exposure unit for writing an image, it is necessary not only to provide the compatibility between a function of shielding the scene and a function of transmitting exposure light, but also to record an image of similar contrast on each of the stacked image record media.
A sheet enabling an image to be recorded not only on one side, but also on double sides and an image record apparatus for recording an image on both sides of the sheet has been developed.
For example, JP-A-Hei. 5-165002 discloses a double-sided record sheet and a double-sided image record apparatus for recording an image on both sides of the record sheet.
FIG. 17 is a drawing to show the double-sided image record apparatus disclosed in JP-A-5-165002.
In FIG. 17, the double-sided image record apparatus comprises an image record medium 100, light exposure units 102A and 102B, voltage application unit 103, and electrodes 112A and 112B. The image record medium 100 comprises an electrode 112C, substrates 111A and 111B formed on both sides of the electrode 112C and image record layers 104A and 104B for indicating a transparent state and an opaque state depending on light beams different in wavelength in a specific frequency electric field. The image record layer 104A, 104B uses a material including polymeric liquid crystal, monomeric liquid crystal, and photosensitive molecules.
However, when an image recorded on the surface of the image record medium with images recorded on both sides is observed, if the image recorded on the back or the scene through the medium is seen through the surface, the visibility and the display quality of the image are impaired remarkably. Then, it is common practice to place a light shield member between the image record layers on the surface and the back of the medium so that the image on one side is not seen through the other. In the disclosed double-sided image record apparatus, the electrode 112C comprising a metal-evaporated layer and a resin with metal powder or carbon dispersed corresponds substantially to the light shield member.
If such a light shield member is placed, however, light from light exposure unit is also shielded and thus it is necessary to place light exposure unit on both sides of the image record medium or reverse the image record medium after exposing one side to expose the other; there is a problem of upsizing the image record apparatus and increasing the cost.

Image record medium and image record apparatus


A variable decision threshold apparatus includes a comparator for receiving the electrical signal and for comparing it to a threshold level. A signal strength monitor monitors the strength of the electrical signal and a scaler scales the decision threshold level to the measured amplitude of the electrical signal so that the percentage set as the threshold level is maintained.

In a digital communications system, data is represented by a number of discrete signal levels, for example, where the system allows only two discrete signal levels, the digital system is known as a binary system. In a binary system, the discrete signal levels are named bits and are given a LOGIC 1 or a LOGIC 0 value. In an optical communications system employing a binary system, a data stream comprising on (LOGIC 1) and off (LOGIC 0) bits can be transmitted by a transmitter in the form of an optical signal across an optical network of fibres and amplifiers to a receiver.
In order to interpret the transmitted data stream, the optical signal can be detected at the receiver by a photodetector to generate an electrical signal. On being communicated to a comparator, for example, a limiting amplifier, the electrical signal is compared to one or more threshold levels. A threshold level is a signal level, for example a voltage, defining a boundary between the upper and lower signal levels (the amplitude) of the electrical signal. An electrical signal having a signal level above the threshold is given a LOGIC 1 value, and an electrical signal having a signal level below the threshold is given a LOGIC 0 value. A threshold level can be expressed as a percentage of the amplitude of the electrical signal by:
                              Threshold                                                              %                =                              (                                                                                V                    TH                                    -                                      V                                          D                                                                                C                                                                                V                  AMP                                            +                              1                2                                      )                    ×          100                                    (        1        )
Where, VTH is the threshold level expressed as a voltage; VDC is a DC level of the electrical signal representing an average fixed reference value of the amplitude of the electrical signal; and VAMP is the amplitude of the electrical signal expressed as a voltage being the difference between the upper and lower voltage levels of the electrical signal.
A measure of the quality of a communications link between a receiver and a transmitter is known as a Bit Error Rate (BER). The BER is a measure of the fraction of transmitted bits incorrectly interpreted at the receiver. For adequate performance of the communications link, a Network Equipment Manufacturer (NEM) typically requires a BER below one error bit in 1010 bits. One significant factor affecting the BER of an optical communications system is the signal to noise ratio of the optical signal. Noise can be added to the optical signal as a result of factors such as amplification of the optical signal, timing jitter and the bandwidth limitations of components employed in the communications network which process the data stream; As is known in the art, in terms of a data stream viewed as an eye diagram on a digital communications analyser, noise can cause the eye to close and optical amplifiers can add noise that cause the eye to become asymmetrical. As the eye closes and becomes asymmetrical, the margin or distance between the two logic levels becomes less, and therefore errors in determining whether a received signal represents a LOGIC 1 or a LOGIC 0 bit increases, thereby increasing the BER.
For example, for a 101010 data stream having a high signal to noise ratio and therefore a nearly ideal eye diagram, the optimum threshold level would correspond to substantially half-way between the maximum and minimum signal levels of the electrical signal generated by the receiver in response to the received data stream. Such a threshold level is known as a 50% threshold level in the art and can be derived from equation (1) above. However, should the 101010 data stream undergo several stages of amplification prior to being received at the receiver, noise may be introduced into the data stream causing the probability statistics of the data stream to change and the eye diagram to become asymmetrical. For such a data stream, the optimum threshold level could be at a signal level corresponding to a 40% threshold level. In order to maintain the BER at an acceptable level, it is known in the art that the optimum threshold level must be determined accurately and maintained to within a few per cent of its optimum value.
It is common for the threshold level to be controlled by a microprocessor, for example, it is known to interface a Digital-to-Analogue Converter (DAC) to a limiting amplifier. A suitable DAC may comprise 10 bits to provide 1024 discrete output levels and is typically programmed to operate over the full amplitude range of the electrical signal. For example, if the DAC is set for an amplitude of 400 mV, each discrete level of the 1024 discrete levels is set to a step resolution of 0.39 mV and is therefore capable of adjusting the threshold level to a resolution of 0.1% over the full amplitude range of the electrical signal. However, should the amplitude of the electrical signal fall to, for example, 5 mV as a result of a fall in the power of the received optical signal, each discrete level at a step resolution of 0.39 mV would only be capable of adjusting the threshold level to a resolution of 8% of the 5 mV amplitude of the electrical signal. Such a coarse resolution can result in poor control of the threshold value and therefore an increase in the BER as discussed above.
As such, NEMs must have the capacity to select an optimum threshold level at any value from the full amplitude range of an electrical signal. Also, a NEM must have the capability, at a suitable resolution, to maintain control of the threshold level to within a few per cent of its optimum value in an event of a change in power of a received optical signal and hence a change in amplitude of the generated electrical signal.
In an attempt to meet the above requirements, it is known to employ an Automatic Gain Control (AGC) amplifier prior to the limiting amplifier in order to provide a fixed value for the amplitude of the generated electrical signal independently of a change in the power of the received optical signal. In the above case, the AGC output would be fixed to 400 mV thereby ensuring that the amplitude range of the electrical signal communicated to limiting amplifier is fixed at 400 mV despite a fall in input signal power in order to ensure that the DAC is capable of adjusting the threshold level to a resolution of 0.1% over all input optical signal powers. A disadvantage of employing an AGC amplifier is that the extra amplifier increases manufacturing costs and power consumption in addition to using valuable circuit real estate.
Alternatively, an adaptive decision threshold setting circuit such as one disclosed in GB 2 293 931 can be employed. In GB 2 293 931, an input digital signal developed by a signal source is time averaged and mirrored by a current mirror to generate one or more decision thresholds. The thresholds may be a set or variable fraction of the average current and track any variation in the average current obviating a need for an AGC amplifier. A disadvantage of GB 2 293 931 is that in order to keep noise in the low level digital signal developed by the signal source to a minimum, it is necessary to redesign existing integrated circuits to realise the design on the first amplifier chip, thereby increasing costs and development times.

Avago Technologies Fiber IP(Singapore) Pte. Ltd.


The present invention relates to methods of producing a polypeptide, comprising: (a) introducing into a respiratory-defective mutant of a cell (i) one or more first nucleic acid sequences which complement the respiratory defect and (ii) a second nucleic acid sequence which encodes the polypeptide; (b) cultivating the cell containing the first and second nucleic acid sequences in a culture medium under aerobic conditions suitable for expression of the first and second nucleic acid sequences; and (c) isolating the polypeptide from the cultivation medium of the cell. The present invention also relates to methods for disrupting a gene in a respiratory-deficient mutant cell. The present invention further relates to respiratory-deficient mutant cells and methods for obtaining such mutant cells.

1. Field of the Invention
The present invention relates to methods of producing polypeptides in respiratory-deficient mutant cells. The present invention also relates to methods for disrupting a gene in a respiratory-deficient mutant cell. The invention further relates to respiratory-deficient mutant cells and methods for obtaining such mutant cells.
2. Description of the Related Art
There are a variety of methods for selecting and maintaining a recombinant DNA molecule in a host cell. One method involves complementation of an auxotrophic mutation with a cloned wild-type gene. However, maintenance of complementing DNA in complex media is difficult where, for example, an amino acid or a nucleic acid may be present, which also relieves the auxotrophy. Another method employs marker genes that can be selected in wild-type recipients, particularly, resistance marker genes such as antibiotic resistance genes. The use of antibiotic resistance genes generally requires an expensive antibiotic in the culture medium and its subsequent removal from the desired product. A further method involves the use of a lethal chromosomal marker which is repressed by a gene borne by a recombinant DNA cloning vector. This method has been successfully applied to bacteria, but is difficult to apply to other hosts, e.g., fungi. Furthermore, the method requires the use of a plasmid-borne repressor gene that does not interfere with the transcriptional activating sequence driving expression of the recombinant DNA molecule.
The instability of an expression vector containing a recombinant DNA molecule in a host cell poses a serious problem for the consistent high-level expression of the recombinant DNA molecule. Upon subculturing of the transformant, the yield of a product encoded by the recombinant DNA molecule may decline dramatically and unpredictably. This is particularly true if expression of the recombinant DNA molecule imparts a deleterious effect on the host cell, e.g., toxicity of the expressed product toward the cell. It is desirable that a microbial culture of the transformant containing the recombinant DNA molecule be selected and maintained so that substantially all of the microbial cells in the culture will contain the recombinant DNA molecule.
There is a particular need in the art for alternative selection and maintenance systems that insure both high level expression and genetic stability of a transformant during cultivation.
U.S. Pat. No. 4,902,620 discloses the introduction of a heme biosynthetic enzyme (5-aminolevulinic acid synthase) gene into a heme-deficient cell for the production of 5-aminolevulinic acid.
It is an object of the present invention to provide new methods for selecting and maintaining recombinant cells in the heterologous expression of genes.

Methods for producing polypeptides in respiratory-deficient cells


A query framework system is provided. The query framework system comprises a query framework service for consuming a query and returning a result set, a provider application programming interface for defining a consistent application programming interface for providers, one or more providers incorporating query processing logic, and a configuration repository for storing the list of the providers in the query framework system and their properties.

Prior business intelligence (BI) query engines are not extensible, are not data agnostic, and can not support the various requirements of a corporate performance management or a BI solution in a consistent manner. They can only support some of the BI requirements using fragmented and inconsistent sub-engines, each providing a subset of the solution. This inconsistency filters up to the front end of the solution and present the BI user with an inconsistent user experience.

International Business Machines Corporation


The image forming apparatus is provided with: plural image carriers; and plural exposure apparatuses that are arranged corresponding to the plural image carriers respectively. The exposure apparatus has a light emitting element member that exposes the image carrier and is arranged on a substrate. A predetermined exposure apparatus among the plural exposure apparatuses includes a heating unit that heats the substrate, and other exposure apparatus other than the predetermined exposure apparatus does not include the heating unit.

1. Technical Field
The present invention relates to an image forming apparatus and the like such as a printer and a copy machine, an exposure apparatus and an image forming method.
2. Related Art
In a color image forming apparatus with an electrophotographic type such as a printer and a copy machine, as an exposure apparatus that is used at the time of forming color toner images, there is a known apparatus that is formed by arranging light emitting elements such as LED in the main scanning direction. In such an exposure apparatus, since heat is generated at the time of lighting the light emitting elements, a substrate that supports the light emitting elements elongates and retracts due to an influence of the heat. Therefore, different displacement of the light emitting elements is generated for each exposure apparatus. When the color toner images are combined, there is sometimes a case where color drift is generated.

Image forming apparatus, exposure apparatus and image forming method


The present invention relates to synthetic peptides having selectively protected amines of untargeted sites and to methods for production thereof and for specifically conjugating PEG to targeted sites of the synthetic peptides using the same. The present invention provides a much higher yield of PEG conjugated peptides in which PEG is specifically combined to amines at targeted sites.

Technologies for conjugating PEG to peptides and proteins are based on Davis and Abuchowski study (Abuchowski A. et al., J. Biol. Chem., 252, 3571-3581, 1977; Abuchowski A. et al., J. Biol. Chem., 252, 3582-3586, 1977). PEG is a polymer which is hydrophilic, biocompatible and harmless having the structure of H(OCH2CH2)nOH and it is known that in case of being conjugated to peptide and protein, it inhibits enzymatic metabolism via steric hindrance as the same way as sugar chain in glycoprotein does, decreases renal glomerular filtration with increased molecular size of peptide and protein having conjugated PEGs, thereby increasing the duration of physiological activity. Covalent bond between polypeptide and PEG was published in U.S. Pat. No. 4,179,337, and it was described that modification of proteins and enzymes with PEG leads to reduced immunogenicity and antigenicity and increased half life within blood.
For covalent bonding of PEG to polypeptide, it is necessary that "activation" process of converting the terminal hydroxyl moiety of PEG to a reactive functional group. As an "activated PEG", alkylating agents such as PEG aldehydes, PEG epoxides and PEG tresylates, and acylating agents such as PEG esters can be enumerated, and the representative example is PEG succinimidyl succinate. Poly(ethyleneglycol)-N-succinimide carbonate and producing method thereof was known from Abuchowski et al., Cancer Biochem. Biophys. 7:175-186(1984) and U.S. Pat. No. 512,614 etc. PEGs in molecular range of 2,000-40,000 can be employed and PEGs such as methoxylated PEGs and branched PEGs can be used. The branched PEG can be represented with the structure of R(-PEG-OH)m [herein, R defines central core moiety such as pentaerythritol or glycerol, m defines the number of branching arm in a range of 3-100]. Hydroxyl group can be used for chemical modification. Other branched PEG with the structure of (CH3O-PEG-)pR—X (WO96/21469) is employed [herein, p is 2 to 3, R represents central core moiety such as lysine and glycerol, and X defines a functional group such as carboxyl group used for activation. Pendant PEG of another branched PEG has functional group such as carboxyl moiety on PEG backbone, other than terminus of PEG chain. All these branched PEGs can be used via "activation" as described previously.
In the reaction of conjugating "activated" PEGs to peptide amines, generally, PEGs bond to one or more amines nonspecifically, thus the core of this technology lies in the method of specifically combining PEG molecules to amines at specific positions. However, in case of peptides containing at least one lysine within the amino acid sequence, as two or more amines exist therein, it is very difficult to specifically conjugate PEGs to amines at specific sites. In case PEGs are conjugated to peptide according to general methods, various conjugates can be generated, from a conjugate having one conjugated PEG to a conjugate having multiple-conjugated PEGs as many as the number of amines, and even in case of the conjugate having one PEG (a mono-PEG conjugate), positional isomers in which conjugation sites of PEG are different one another, can be formed. Usually, as PEG conjugates of peptide differ in activity and enzymatic metabolism according to the number of combined PEGs and combined sites thereof, the method producing such mixture containing various conjugates is disadvantageous for the reason of very low activity yield and being a mixture. To separate and purify specific isomer from the mixture is very complicated, accompanied by very low yield and high cost. To compensate such disadvantages, various methods for site-specific PEGylation have been proposed, however, efficient methods for specific conjugation of PEGs to amines on specific positions has not yet been developed.
Chem. Pharm. Bull. 39(12): 3373-3375(1991) reported on a conjugate of fibronectin-related tripeptide(Arg-Gly-Asp) and amino-poly(ethyleneglycol) and activity thereof. Herein, a method for preparing PEG conjugate by combining amino PEG to aspartic acid activated with dicyclohexylcarbodiimide(DCC)/1-hydroxybenzotriazole(HOBt), was proposed. However, this method is defective in that it can be used only for modification of C-terminus and racemization of adjacent amino acids can occur during the C-terminal activation of peptide. Such racemization can occur in every amino acids except glycine, resulting in reduction of activity of peptide.
Methods for combining monomethoxy poly(ethyleneglycol)(mPEG) or polyvinylalcohol(PVA) to peptide using synthetic resin were published in Journal of Protein Chemistry 10(6):623-627(1991). Since only the conjugate in which a single polymer is combined to N-terminus of the peptide from the method, it fails to provide a method for combining PEG to positions that can maximize the effect of PEGylation (maximizing the duration of peptide activity and minimizing enzymatic metabolism).
PCT patent application No. PCT/US94/06953(1994) provides methods for preparing site-specific PEG peptide in which PEG is introduced during synthetic process of the peptide. That is, it provides a method for preparing PEG-conjugated peptide in which peptide is partially synthesized until its sequence reaches lysine at targeted position, and then PEG is combined, and finally the remaining portion of the peptide is synthesized to complete PEG peptide, a method for preparing PEG-conjugated peptide by using, as the lysine of targeted site, lysine in which Nα-amine thereof was protected with Fmoc(9-fluorenylmethoxycarbonyl) and branched amine thereof was combined with PEG, and a method wherein peptide fragment having PEGs combined to the amines of targeted sitse and the remaining peptide fragment were separately synthesized and combined to complete the PEG-conjugated peptide. Nevertheless, such methods might bring undesirable result due to the effect of the previously combined PEG on subsequent step of the synthesis. For example, in case PEG is introduced during the peptide synthesis and synthesis of the remaining portion is to be continued, a peptide lacking at least one amino acid of the amino acid sequence might be produced, and such peptide can b harmful to a living body and its purification is almost impossible. Therefore, such method is not desirable as a method for preparing a PEG-conjugated peptide usable as a medicine.
PCT patent application No. PCT/EP98/07748 provides methods for combining PEG to amine of GRF in an organic solvent and purifying the resulting mixture of Lys(PEG)12-GRF, Lys(PEG)21-GRF, Lys(PEG)12,21-GRF and [Nα-PEG-Try1, Lys(PEG)12,21]-GRF by gel chromatography and reverse phase chromatography. However, this method cannot provide specificity between amine moieties of Nα, Lys12 and Lys21. Said patent also provides methods for synthesis of [Lys(Alloc)12,21]-GRF(1-29) and [Nα-isopropyl-Try1, Lys(Alloc)12]-GRF(1-29) and specific PEGylation using them, though, in case of [Lys(Alloc)12,21]-GRF(1-29), PEG can be conjugated to only Nα amine, and fails to provide a preparing method for Lys21-PEG conjugate which is most effective as described in said patent. In addition, in case PEG conjugate is prepared by using [Nα-isopropyl-Try1, Lys(Alloc)12]-GRF(1-29), not PEG conjugate of GRF(1-29)-NH2 but PEG conjugate of [Nα-isopropyl-Try1]-GRF(1-29)-NH2, i.e. [Nα-isopropyl-Try1, Lys(PEG)21]-GRF(1-29) is to be formed. Therefore, this method fails to provide completely specific PEGylation for the original peptide having N-terminal amine, GRF(1-29)-NH2.
The inventors of the present invention intended to develop specific PEGylation by which product yield can be noticeably raised and efforts and cost needed for separation and purification of the final product can be reduced, by forming the final product in which PEGs are conjugated only to amines at targeted sites while preventing the formation of impurity product having PEGs conjugated to amines of untargeted sites.
The present invention provides method for preparing specific PEG-conjugated peptide in which the effect of PEG conjugation is maximized by allowing PEGs to be conjugated to amines at targeted sites only with complete selectivity.

Peptides having protected amines of untargeted sites, methods for production thereof and of specifically conjugated PEG peptides using the same