The present invention provides hydrophobic heparin conjugates that are soluble in organic solvents but not in water, a method of preparing them, and a method of using them. Particularly, the present invention provides hydrophobic heparin conjugates that are prepared by covalently binding a polymer to heparin and a hydrophobic agent to the polymer. The hydrophobic heparin conjugates of the present invention maintain a good antithrombogenic effect and are insoluble in water due to their hydrophobicity, so they can be effectively used as coating agents for modifying the surfaces of medical devices.

The present invention relates to hydrophobic multicomponent heparin conjugates, which are soluble in certain organic solvents but not in water, and to methods of using and making thereof. Particularly, the present invention relates to hydrophobic multicomponent heparin conjugates that are prepared by covalently binding polymeric and hydrophobic materials to heparin and that are used for treatment of patients as a antithrombogenic agent.
Thromboresistence of vascular walls requires an endothelial lining that is compatible with platelets and the plasma coagulation system. Unlike artificial vascular materials, endothelial linings do not induce serine protease activity during the coagulation process. However, when coagulability of blood is increased, the endothelium inactivates thrombin and other possible coagulation factors. Generally, the inflow site of thrombin is known to be at the surface of endothelium cells (B. Awbrey et al. J. Biol. Chem., 254, 4092–4095, 1979), and the glycosaminoglycan layer on endothelial cells is also known to have thrombin-binding sites. It is reported that if those thrombin binding sites are bound to enzymes such as serine protease, the enzymes are inactivated by antithrombin III in blood serum (C. Busch et al., J. Clin. Invest., 726–729, 1982; M. Dryjski et al., Thromb. Res., 32, 355–363, 1983).
After it was reported that an analogous structure for antithrombin binding exists in heparin molecules (J. A. Marcum et al., J. Clin. Invest., 74, 341–350, 1984; J. A Marcum et al., Biochem. Biophys. Res. Comm., 126, 365–372, 1985), methods for introducing heparin into or on the surface of solid materials to produce endothelium-like thromboresistent properties was soon developed and commercialized. Artificial surfaces, which have obtained endothelium-like thromboresistent properties by using heparin and the like can be widely used for the development of medical techniques.
Among those studies, various methods for improving blood compatibility of macromolecular surface using heparin were developed. Grode et al. synthesized heparin-silicon rubber using cyanuric chloride and radiation grafting (Grode et al., J. Biomed. Mater. Res. Symp., 3, 77–84, 1972). Merrill et al. also synthesized a conjugate wherein polyvinyl alcohol was covalently bound to heparin by glutaraldehyde cross linking (Merrill et al., J. Appl. Physiol., 29, 723–728, 1970). Eriksson and Gillerg developed a cross-linked heparin monomer in which anionic heparin was absorbed on the surface of polypropylene by heparin cross linking and use of a cationic surfactant (Eriksson and Gillerg, J. Biomed. Mater. Res., 1, 301–312, 1967).
Goosen and Sefton synthesized heparinized a styrene-butadiene-styrene elastomer (Goosen and Sefton, Thromb. Res., 20, 543–554, 1980). And, Miyura et al. designed a method of prolongation of plasma recalcification by fixing heparin on Sepharose® or polyhydroxymethacrylate (Miyura et al., J. Biomed. Mater. Res., 14, 619–630, 1980).
Jacobs et al. synthesized a covalently bonded complex of heparin and prostaglandin E1 (Jacobs et al., J. Biomed. Mater. Res., 23, 611–630, 1989). The above heparin complex was fixed on urethane by diamino-terminated polyethylene oxides, and this fixed complex was very effective for prohibiting thrombin formation. Hennink et al. developed a covalently bonded complex of heparin and human serum albumin (Hennink et al., Thromb. Res., 29, 1–13, 1983). This complex increased blood compatibility of macromolecular surfaces that were in contact with blood.
Nagaoka et al. reported the results of animal experiments that showed that a polyethylene oxide (PEO) hydrophilic spacer fixed on a macromolecular surface inhibited the attachment of platelets by absorption of blood proteins and dynamic repulsion (Nagaoka et al., Trans. Am. Soc. Artif. Intern. Organs., 10, 76—76, 1987). The inhibitory effect on platelet attachment by a spacer fixed on a heparinized surface was confirmed by Kim and Ebert (Kim and Ebert, Thromb. Res., 26, 43–57, 1982). They proved that nticoagulant activity of fixed heparin increased according to the length of spacer.
Further, Tay et al. showed that 1) a long spacer, such as PEO, made binding heparin with antithrombin III and thrombin easier; 2) heparin coupled to end groups of polyvinylalcohol was more accessible than heparin coupled to amino groups on non-terminal units of heparin macromolecules; and 3) heparin units on the surface obstructed the access of antithrombin III and thrombin (Tay et al., Biomaterials, 10, 11–15, 1989).
Schmer covalently bound heparin to agarose by using spacers such as thiophosgene or carbodiimide (Schmer, Trans. Am. Soc. Artif. Intern. Organs., 18, 321–324, 1972), and this spacer-fixed heparin had advanced binding capacity to antithrombin III.
Danishefsky and Tzeng produced heparin-agarose macromolecules by using an aminoethyl spacer (Danishefsky and Tzeng, Thromb. Res., 4, 237–246, 1974). Park et al. fixed heparin on a biomer by using a PEO spacer, and they reported that the length of such spacers should be at least 3,400 Daltons to optimize anticoagulation activity of the fixed heparin (Park et al., J. Biomed. Mater. Res., 22, 977–992, 1988). Also, heparin was fixed on the surface of spacers to optimize anticoagulation activity and to amplify surface density of the spacers. (Lin et al., J. Biomed. Mater. Res., 25, 791–795, 1991; Piao et al., Trans. Am. Soc. Artif. Intern. Organs., 38, 638–643, 1992).
Moreover, spacer systems using heparin were used for synthesis of copolymers. Triblock copolymers such as PEO-PDMS-heparin and PDMS-PEO heparin were synthesized (Grainger et al., J. Biomed. Mater. Res., 22, 231–249, 1988). These triblock copolymers coated on a segmented polyurethane surface increased nonthrombogenicity even under low flow. Vulic et al. reported a method of synthesizing polyurethane-PEO-heparin (Vulic et al., J. Polym. Sci. A, Polym. Chem., 26, 381–391, 1988), which was a modification of the solvent casting method. According to this method, coating was easy but synthesis of the heparin complex with polyurethane or polyethylene glycol was not due to problems of low efficiency and of requiring an excessive amount of solvent to suppress cross linking of heparin during the synthesis process.
To overcome the foregoing and other disadvantages, a method of making a heparin complex, comprising heparin and hydrophobic macromolecules, has been developed in which heparin is combined first with a macromolecule having multi-functional groups and then with hydrophobic materials. The result is a synthesized hydrophobic multicomponent heparin conjugate that is soluble in organic solvents but not in water. Finally, the hydrophobic multicomponent heparin conjugates of the present invention can easily be coated on the surface of all medical instruments comprising macromolecules or metals, and such coated instruments exhibit high anti-thrombosis.

This patent is subject to a terminal disclaimer.

Hydrophobic multicomponent heparin conjugates, a preparing method and a use thereof


A display device includes an insulating substrate; a plurality of gate wires formed on the insulating substrate, the plurality of gate wires including a gate electrode; a gate insulating layer covering the plurality of gate wires; a transparent electrode layer formed on the gate insulating layer, the transparent electrode layer including a source electrode and a drain electrode disposed about the gate electrode and spaced apart from each other to define a channel region disposed therebetween; a plurality of data wires covering a predetermined portion of the transparent electrode layer and being crossed insulatedly with the plurality of gate wires to define pixels; and an organic semiconductor layer formed on the channel region for each pixel, a predetermined portion of the organic semiconductor layer being operatively connected with the source electrode, the drain electrode, and the gate electrode to form a transistor having an improved characteristic and a novel structure.

(a) Field of the Invention
The present invention relates to a display device and a method for manufacturing the same, and more particularly, to a display device comprising an organic thin film transistor and a method for manufacturing the same.
(b) Description of the Related Art
Recently, flat panel display devices having the dual advantages of smaller size and lighter weight have received increasing attention in the marketplace. Such a flat display device typically comprises a liquid crystal display (LCD) and an organic light emitting diode (OLED). In general, the liquid crystal display device comprises a thin film transistor substrate on which a thin film transistor is provided, a color filter substrate on which a color filter is provided and a liquid crystal layer interposed between both substrates.
In this case, the thin film transistor substrate is the switching and driving element for controlling the operation of each pixel where each thin film transistor comprises a gate electrode, a source electrode and a drain electrode spaced from each other with the gate electrode as a center to define a channel region and a semiconductor layer. Amorphous silicon or poly silicon typically forms the semiconductor layer. According to a recent study related to applying an organic semiconductor to the semiconductor layer, the organic semiconductor can be formed at a normal temperature and pressure, and so that the manufacturing costs may be reduced and the organic semiconductor layer can be formed on a plastic substrate which is vulnerable to heat.
However, a work function of organic semiconductor is larger than that of aluminum, chrome, molybdenum or the like used as the source and drain electrodes, and so a characteristic of the organic thin film transistor is undesirable. Accordingly, instead of the above metals, transparent electrode material such as indium tin oxide (ITO) or indium zinc oxide (IZO) having a work function which is similar to or larger than that of organic semiconductor is used for forming the source electrode and the drain electrode. However, ITO or IZO is disadvantageous in that a resistance of ITO or IZO is large so that the electrode made of ITO or IZO is not suited to the data wires. In order to solve the above problem, an organic thin film transistor having a buried data wire structure in which data wires made of metal with a low resistance are provided at a lower side, a source electrode and a drain electrode is made of indium tin oxide or indium zinc oxide and data wires are connected to the source and drain electrodes has been developed and manufactured.
However, the above mentioned buried data wire structure is not effective in that a manufacturing process is complicated, and a great number of masks are required for carrying out the manufacturing process so that manufacturing cost is increased.

Display device and method for manufacturing the same


A compound represented by formula (I-1):

As for heterocyclic compounds, compounds in which two heterocycles are condensed to a benzene ring are hitherto known (see, for example, JP-A-63-150273 ("JP-A" means unexamined published Japanese patent application), JP-A-4-85547, JP-T-5-506428 ("JP-T" means published Japanese translation of PCT application), and Journal of the American Chemical Society, 1995, Vol. 117, pages 9995 to 10002). In these publications, there are disclosures relating to tetrathiafulvalene analogs probably because these heterocyclic compounds interested mainly in a charge-transfer complex. Therefore, a majority of the condensed heterocycles disclosed therein is dithiol rings. More specifically, most of the dithiol rings are those having a structure wherein an alkylmercapto group or a dithiol ring is substituted via exomethylene at 2-position of the dithiol ring.
Further, with respect to the use of these compounds having such a structure for various kinds of functional materials, there are one case where these compounds are used as a charge-transfer complex for use in an organic electrophotographic material (see, for example, JP-A-4-85547), and another case where these compounds are used as an inert carbon free radical partial structure (see, for example, JP-T-5-506428). However, these structures are limited to a narrow scope whereby desirable properties can be provided. Since then, new compounds have not been found, probably because studies on other applications of the dithiol rings have not been tried.
Ultraviolet absorbents have been used in combination with various resins for providing the resins with ultraviolet-absorptivity. Both inorganic and organic ultraviolet absorbents are used as the ultraviolet absorbent. The inorganic ultraviolet absorbents (see, for example, JP-A-5-339033, JP-A-5-345639 and JP-A-6-56466) are superior in durability properties such as weather resistance and heat resistance. However, the freedom in selecting the compound is limited, because the absorption wavelength is determined by the band gap of the compound. In addition, there is no inorganic absorbent that absorbs the light in a long-wavelength ultraviolet (UV-A) range of around 400 nm. And any such absorbent that absorbs long-wavelength ultraviolet would have color because it would have absorption also in the visible range.
In contrast, the freedom in designing the absorbent structure is much wider for organic ultraviolet absorbents, and thus, it is possible to obtain absorbents having various absorption wavelengths by designing the absorbent chemical structure properly.
Various organic ultraviolet absorbent systems have been studied, and for absorption in the long-wavelength ultraviolet range, it is conceivable either to use an absorbent having the wavelength of maximal absorption in the long-wavelength ultraviolet range or to use a high concentration of absorbent. However, the absorbents described in, for example, JP-A-6-145387 and JP-A-2003-177235 having the wavelength of maximal absorption in the long-wavelength ultraviolet range are inferior in light stability, and their absorption capacity declines over time.
In contrast, benzophenone- and benzotriazole-based ultraviolet absorbents are relatively higher in light stability, and increase in concentration or film thickness leads to relatively clean blocking of the light in the longer-wavelength range (see, for example, JP-T-2005-517787 and JP-A-7-285927). However, when such an ultraviolet absorbent is applied as mixed with a resin or the like, the film thickness is limited to several tens of μm at the most. For utilizing the film thickness to block the light in the longer-wavelength range, it is necessary to add the ultraviolet absorbent to a considerably high concentration. However, simple increase in concentration only results in a problem of precipitation and bleed-out of the ultraviolet absorbent during long-term use. In addition, among benzophenone-based and benzotriazole-based ultraviolet absorbents, there are some ultraviolet absorbents that may cause concern about skin irritation and accumulation in body. Therefore, intensive care should have been given to these compounds during use.
Meanwhile, as for the heterocyclic compound, compounds represented by any one of the following Formulae (S-1) to (S-5) are known (see, for example, JP-A-63-150273, Tetrahedron Letters, 1977, Vol. 26, page 2223). These compounds interested only in a charge-transfer complex component and an intermediate thereof. In fact, these compounds absorb little visible light in solution. Therefore, they have never been considered the use for a coloring agent.

Heterocyclic compound, ultraviolet absorbent and composition containing the same

Abstract: wherein R21, R22, R23 and R24 each independently represent a hydrogen atom or a monovalent substituent, with the proviso that compounds, in which R21, R22, R23 and R24 each are an alkylthio group, are excluded; R21 and R22 and/or R23 and R24 each may bond to each other to form a ring, with the proviso that compounds, in which the formed ring is a dithiol ring or a dithiolane ring, are excluded;        R25 and R26 each independently represent a hydrogen atom or a monovalent substituent;        X21, X22, X23 and X24 each independently represent a hetero atom;        compounds, wherein R21, R22, R23 and R24 each represent a cyan group; X21, X22, X23 and X24 each represent a sulfur atom; and R25 and R26 each represent a hydroxyl group or a hydrogen atom, are excluded; and        compounds, wherein R21 and R23 each represent a hydrogen atom; R22 and R24 each represent an arylcarbonyl group; X21, X22, X23 and X24 each represent a sulfur atom; and R25 and R26 each represent a hydroxyl group, are excluded; and an ultraviolet absorbent, which has molecular weight of 10,000 or less and molar extinction coefficient at the maximum absorption wavelength of the ultraviolet absorbent of 80,000 or more.


A dental strip comprised of uniformly thick, dead soft polymer, for use as a matrix in molding hardenable restorative materials. Matrixing processes for the strip permit the formation of interproximally contacting restorations without wedging; and the formation of composite restorations with smooth interproximal margins. Other processes for the strip permit the formation of removable restorations which are separated from prepared tooth surfaces by the strip; the formation of restorations with reduced resin excess; and stabilization of the strip on dental surfaces by affixing with a temporary adhesive.

1. Field of Invention
This invention relates to dental restorations, specifically to the contouring of restorative material utilizing matrices and burnishable.
2. Description of Prior Art
Dental matrices of the art are flat, flexible strips of material which may be contoured into shapes which resemble surfaces of teeth. Matrix strips are manipulated to approximate the desired shape of the restoration. The strips provide a contourable surface, whereby hardenable restorative materials may be partially contained and manipulated into desirable contours prior to hardening. Matrices of the art are comprised of flat strips of thin steel, flat strips of mylar, or other similar materials.
The metal strips have a thickness ranging from 0.001 to 0.002 inches. Metal matrices are used more often for restoring posterior teeth, as they are less likely to tear than transparent strips.
Transparent strips are primarily used as matrix strips for esthetic restorations. Theses are typically comprised of 0.002 inch thick acetate, known as Mylar (3M). The transparency provides access for the curing light, as the strip frequently covers the restoration.
Metal and Mylar strips of less thickness than those cited tend to wrinkle or tear, such as when fitting through interproximal contact areas between teeth. It is not practical for a dentist to reduce the thickness of mylar or metal strips, such as by burnishing.
Metal and transparent strips are typically flat, and relatively stiff, and exhibit substantial memory for their shapes. As a result, they readily cut the interproximal gingival papilla, and initiate bleeding. Bleeding is a major impediment for restoration bond strengths and esthetics. Matrix memory also tends to interfere with the operator's efforts to mold the restorative material to physiological contours. As such, restorations formed with matrices of the art tend to be molded somewhat nonphysiologically. This creates any of several problems, including overhangs, food traps, plaque and stain traps, open contacts, ledges, shredding dental floss, open embrasures, poor esthetics, chronic gingival inflammation, voids, and so on.
Further, matrices of the art must be forcefully retained against the critical gingival margin of a tooth cavity preparation as uniformly as is possible. Otherwise the matrix tends to pull away from the restorative material, and the margins. This requires a matrix retainer device, or a continuous operator finger pressure. Such retaining of matrices of the art interferes with the ease of molding restorative materials.
A wedge is used to conform matrix strips of the art, as much as possible, to the shape of the gingival margins of the preparation. However, portions of the strip tend to remain a distance from the preparation margins. This permits the restorative material to form undesirable overhangs along the preparation margins.
Wedges are used simultaneously to temporarily, slightly separate the teeth, to compensate for the thickness of the strip. Steel and Mylar matrices do not readily burnish to a reduced thickness. After the restoration is hardened, the strip is removed, and the teeth move back together. As such, the adjacent tooth is able to maintain proper contact with the restorative material. However, wedges tend to traumatize the interdental papillae, and promote bleeding.
Composites are hardenable restorative materials which contain adhesive resins. The curing, or hardening, of such resins is substantially inhibited in the presence of oxygen. An uncured oxygen inhibited resin layer, which forms at the exposed outer surface, facilitates strong bonding to subsequent additions of restorative material. Matrix strips of the art are nonporous, and thus shield the composite from oxygen. As such, they eliminate the oxygen inhibited layer. Further additions of unhardened restorative material to hardened, noninhibited surface material results in substantially weakened bond strengths.
In addition to contouring restorative materials, matrixes of the art also act as separators. Separators can be defined as any material or device which provides a barrier surface to prevent contact between substances. Separators include paints, gels, and strips of various materials. Howard Stean, in "PTFE Tape: A Versatile Material in Restorative Dentistry", DENTAL UPDATE, Vol. 20, No. 4, May 1993, discloses utilizing a soft polymer strip, PTFE (DuPONT Teflon.RTM. polytetrafluoroethylene), tape as a separator. Dr. Stean specifies utilizing the PTFE tape as a barrier to prevent inadvertent adhesion of luting cement with adjacent teeth, when cementing porcelain veneers. The PTFE tape is preferred as a separator because it can be burnished thin, to prevent displacement of porcelain veneers during cementation. In contrast, the thickness of the metal and mylar strips, as separators, would displace veneers from proper positioning on the teeth. As a result, the cleanup of hardened cement was made easier, without compromising the positioning of the veneers.
However, such use of PTFE tape for cementation of porcelain veneers never achieved widespread use for a variety of reasons. The thread seal tape commonly available in plumbing stores is fragile and difficult to use. Further, the process does not specify a technique for inserting the tape between interproximally contacting tooth preparations. Still further, current cementation technique prefers partly hardening the cement without any separator, followed by cleaning the excess cement, and completely hardening the remaining luting cement.
The above matrix strips suffer from a number of disadvantages:
(a) Matrix strip processes specify concurrent use of a wedge to mold a restoration to contact the adjacent tooth. PA1 (b) Matrix strips are not readily burnishable to insubstantial thickness. PA1 (c) The substantial shape memory of matrix strips tends to interfere with shaping unhardened restorative material. PA1 (d) Matrix strips require applied tension to retain their position. PA1 (e) Matrix strips tend to form overhanging restoration margins. PA1 (f) Matrix strips substantially eliminate the oxygen inhibited layer of composite restorative materials. PA1 (g) Matrix strips tend to cut the gingiva when placed to cover gingival margins. PA1 (h) Matrix strips do not absorb bonding resins. PA1 (i) No matrix strip process substantially blocks out all surface undercuts available to restorative material molded in a prepared tooth, and molded against substantially unshimmed interproximal contact areas. PA1 (j) No matrix strip process provides a separating layer between surfaces of a prepared tooth and permanent restorative material against substantially unshimmed interproximal contact areas. PA1 (k) No matrix strip process provides for molding restorative material in a prepared tooth, against substantially unshimmed interproximal contact areas, without unseating during a pliability stage, then hardened, and removed from the tooth, without substantial deformation, fracture, or abrading of the restorative material. PA1 (l) No matrix strip process provides for molding restorative material by impression imprint in a prepared tooth, against substantially unshimmed interproximal contact areas, then hardened, and removed from the tooth, without substantial deformation, fracture, or abrasion. PA1 (m) Processes utilizing matrix strips to form removable permanent restorations specify the use of separators which create separation spaces which are inconsistently too wide or too narrow. PA1 (a) to provide a matrix strip which permits the restorative material to contact the adjacent tooth without requiring the use of a wedge; PA1 (b) to provide a matrix strip which is readily burnishable to insubstantial thickness; PA1 (c) to provide a matrix strip which is dead soft, so that it adapts readily to the desired shape of the restoration, yet stabilizes the shape of the moldable restorative material; PA1 (d) to provide a matrix strip which does not require applied tension to be retained in position; PA1 (e) to provide a matrix strip which facilitates molding restoration margins without overhangs; PA1 (f) to provide a matrix strip which substantially preserves the oxygen inhibited layer of composite restorative materials; PA1 (g) to provide a matrix strip which does not tend to cut the gingiva when placed to cover gingival margins; PA1 (h) to provide a matrix strip which absorbs bonding resins; PA1 (i) to provide a matrix strip which is readily burnishable to insignificant thickness over the interproximal contact area, and separates restorative material from prepared tooth surfaces, such that the restoration is removable from the prepared tooth; PA1 (j) to provide a matrix strip process that substantially blocks out all surface undercuts available to restorative material molded in a prepared tooth, and molded against substantially unshimmed interproximal contact areas; PA1 (k) to provide a matrix strip process that specifies a separating layer between surfaces of a prepared tooth and permanent restorative material molded against substantially unshimmed interproximal contact areas; PA1 (l) to provide a matrix strip process that specifies molding of restorative material in a prepared tooth, and against substantially unshimmed interproximal contact areas, without removal during a pliability stage, partial hardening of the restorative material, and removal of the hardened restorative material from the teeth without substantial deformation, fracture, or abrasion of such material; PA1 (m) to provide a matrix strip process that permits impression imprint molding of unhardened restorative material in a prepared tooth, against substantially unshimmed interproximal contact areas, partial hardening of the restorative material, and then removal of the hardened restorative material without substantial deformation, fracture, or abrading of such material; PA1 (n) to provide a process utilizing matrix strips to form removable permanent restorations that specifies the use of separators which create separation spaces which are consistently adequate; PA1 (o) to provide a matrix strip process that specifies an interproximal contouring matrix for restorative materials, but leaves interproximal contact areas substantially unshimmed, such that a wedge is not needed; PA1 (p) to provide a matrix strip which has an affinity for dental resins, and resin restorative materials.
A device similar to my matrix strip is not obvious because it is not readily apparent that a soft matrix strip can enhance contouring of restorative materials, especially without wedging, facilitate the formation of flush restoration margins, or be readily inserted into tightly contacting interproximal spaces. Neither is it apparent that a matrix strip can preserve the oxygen-inhibited layer of composite restorative materials, or that a semi-opaque matrix permits sufficient curing of light catalyzed restorative materials. Neither is it apparent that a soft polymer strip can permit accurate formation and removal of hardenable restorative material from a prepared tooth, or that stabilizing a soft polymer strip to dental surfaces is a valuable adjunct to dental processes.

Soft polymer dental strip and process therefor


Apparatus is described for component replacement control in a data processing system, with each component being assigned a label that includes a component identifier and a replacement generation value. The apparatus includes a plurality of tables for redundantly storing replacement generation values for each component. The tables that store the replacement generation values are then updated to indicate the incremented replacement generation value for the new component. Circuitry then increments the replacement generation value assigned to a component identity that is replaced by a new component. The circuitry modifies the new component's label to indicate the incremented replacement generation value. When the system is subsequently started, the replacement generation values in each component's label are compared with the replacement generation values in the tables and wherever a match is not found, the component is rejected.

Fault-tolerant systems have been produced for a variety of applications. Some systems achieve fault tolerance by including redundant computing systems, each of which serves as a standby replacement for some or all of the others. So long as the replacement component is identical to the component being replaced, few problems arise in the handling of such replacements. When the component being replaced has been altered during the operation of the data processing system, the replacement component must be similarly altered. If the original failed component or an earlier replacement is reintroduced into the system, a system malfunction will result. This problem is especially severe in data processing systems with large numbers of inherently similar components that are subject to change in distinct and persistent ways as the data processing system operates. For instance, in large parallel computing systems, nodes are employed that include microprocessors with individual disk drive memories. During operation of the parallel processing system, the disks in such nodes store data and thus become "personalized" in accordance with particular system control functions. If such a node fails, is replaced, and the replacement itself fails and is replaced, only the latest replacement has an up-to-date "personality". A means is required to ensure that none of the older versions are permitted to rejoin the system.
The prior art discloses a number of methods and systems for enabling failed part replacements. In U.S. Pat. No. 3,665,418 to Bouricius et al., a fault-tolerant computer system employing stand-by redundancy is described. In the event of a failure of a subassembly, a switching system enables a routing around the failed subsystem. In U.S. Pat. No. 4,633,467 to Abel et al., a system is described for enabling identification of a failed unit when the unit is "buried" within other units and is difficult to monitor. A probability listing is created that enables the fault to be assigned to the unit that is most probably inoperable. In U.S. Pat. No. 4,814,979 to Neches, shut down of one or more processors in a multi-processor system is immediately communicated throughout the system so that an interrupt sequence can be initiated.
In U.S. Pat. No. 4,412,281 to Works, a bus system is used, to which replacement parts are connected. By the expedient of changing an address on the bus, a replacement part can be substituted for a malfunctioning part and enables the continuation of system operations. A similar reassignment method is taught in U.S. Pat. No. 4,442,502 to Friend et al, wherein redundant devices are substituted for malfunctioning devices by the switching of assigned identities.
In U.S. Pat. No. 4,847,837 to Morales et al., a local area network is disclosed which can identify the existence of a fault or error condition in the network, isolate it and alert service personnel to the existence and location of the problem. In U.S. Pat. No. 4,815,076 to Denney et al., a system reconfiguration technique is described that provides several alternatives for recovering from single or multiple component failures. The system locates and tests one or more configurations of a failure scenario and presents possible reconfiguration scenarios in order of preference. US. Pat. No. 4,891,810 to deCorlieu et al., describes a reconfigurable computing system that includes redundant elements. Reconfiguration of the system involves substitution of the redundant element for a malfunctioning element. However, if the system is in a critical computing operation, reconfiguration is postponed to a later time. Chao in U.S. Pat. No. 4,866,712, describes a method and apparatus for fault recovery which includes an error table and action table. When an error count exceeds a threshold, corrective action is initiated in accordance with the aforesaid tables.
U.S. Pat. No. 3,805,039 to Stiffler and U.S. Pat. No. 4,920,497 to Upadhyaya et al. both teach redundant systems wherein inoperable elements are determined and the systems then maps its operations so as to avoid such inoperable elements Stiffler also teaches the use of spare sub-elements as substitutes for the mapped-around elements In U.S. Pat. No. 3,758,761 to Henrion, an electronic system "on a slice" is described wherein substitute redundant subsystems are provided on the slice and are enabled for substitution for malfunctioning subsystems by an external control circuit.
A consistent feature of the prior art is that the redundant replacement component is assumed to be a one-for-one replacement of a malfunctioned component. So long as the malfunctioned component is not personalized during its operation, this is a valid assumption. However, if personalization occurs during operations, a method and apparatus must be provided to enable the system to assure that any replacement is similarly personalized and that no improperly personalized replacement is used as a substitute.
Another problem that occurs with fault-tolerant systems is that a personalized component may malfunction on a transient basis, be replaced by a redundant unit, and at some later time, be reactivated after the transient malfunction has ended. Under such circumstances, the system must have a means for determining that an already-replaced component is attempting to reassert itself into the system. The system must also ensure that no other component has already been activated as a replacement. Under such circumstances, the system should normally ignore such a reassertion action, as the personalization state of the component attempting reinstatement in the system is probably not as up-to-date as the component that replaced it.
Accordingly, it is an object of this invention to provide a data processing system with means for determining a level of personalization of each replaceable component in the system.
It is another object of this invention to provide a fault-tolerant data processing system wherein component replacement is controlled so as to prevent reactivation of a previously failed component that has already been replaced.
It is still another object of this invention to provide a fault-tolerant data processing system which assures that any replacement component is intended for the particular system in which it is being inserted.

Component replacement control for fault-tolerant data processing system

International Business Machines Corporation


Short-chain peptides replicating fragments of functional domains derived from LFA-1 and ICAM-1 parent protein sequences serve to modulate the ICAM/LFA binding interaction. In one aspect of the invention, this modulation serves to block interprotein binding reactivity, as a peptide of the invention binds to a target protein in a manner that precludes the normal binding reaction between ICAM-1 and LFA-1. In another aspect of the invention, this modulation enhances the reactivity of a first peptide, as a second peptide induces a conformational change in the target protein from a first conformation to a second, more reactive, conformation. The peptides are used according to a method including the steps of providing the proteins and applying them to a population of cells.

1. Field of the Invention
The invention pertains to the field of protein chemistry and, more particularly, to short-chain peptides that serve to modulate interprotein interactions. More specifically, these short chain peptides have functional residue sequences that essentially replicate fragments of functional domain sequences in corresponding parent protein molecules, but without replicating the entire parent protein. A first such peptide may be mixed with a second peptide to enhance the functionality of the first peptide by inducing a conformational change in a target protein that is reactive with the first peptide. Similarly, the second peptide may induce a conformational change in the first peptide. Particularly preferred short-chain peptides are taken from parent protein molecule sequences selected from the family of integrins, proteins that react with integrins, and the superfamily of immunoglobulins. The peptides are utilized according to methods including the steps of providing the peptides and applying them to a population of cells.
2. Description of the Prior Art
Certain immune system functions rely upon a critical interprotein binding interaction as a necessary element of immune response. One such binding interaction pertains to a heterophilic interaction between the glycoproteins including Intercellular Adhesion Molecule ("ICAM-1") and Leucocyte Function Associated antigen-1 ("LFA-1"). Examples of published sequences for LFA-1 and ICAM-1 are submitted as Sequence ID No.'s 1, 2, and 3.
It is possible to derive immunological benefits by disrupting the intercellular ICAM/LFA binding interaction through the application of specific monoclonal antibodies ("mAbs"), i.e., anti-ICAM-1 or anti-LFA-1. As reported in Isobe et al., Specific Acceptance of Cardiac Allograft After Treatment With Antibodies to ICAM-1 and LFA-1, 255 SCIENCE 1125-1127 (Feb. 1992), an induced immune tolerance enables the indefinite survival of cardiac allografts between fully incompatible mouse strains subsequent to a six day treatment including the simultaneous application of anti-ICAM-1 and anti-LFA-1 mAbs. Unfortunately, a major problem with the use of mAbs for the purpose of inducing immune-tolerance in a mammal is that these large (e.g., 80-150 kDa) molecules typically also induce an effectiveness-limiting immune response to the mAbs.
LFA-1 has special significance in that it belongs to a family or class of proteins that are known as integrins, and is associated with leukocytes such as T and B cells. The integrin family includes similar glycoproteins that combine two separate protein units as a functional member, i.e., a functional heterodimer formed of a .beta. unit and an .alpha. unit. These respective units each comprise separate proteins that are anchored within interactive proximity to one another, and can extend outwardly from a cytoplasmic domain, across a transmembrane domain, and beyond the cell membrane. In LFA-1, binding avidity for ICAM-1 involves Mg.sup.2+ and Ca.sup.2+ ions that, in part, govern the interaction between the .beta. and .alpha. units.
The integrin family may be subdivided into two groups wherein common group members share common .beta. units. A first group of proteins share the common .beta.1 (CD29) unit, and typically function by binding to extracellular matrix proteins. This first group includes the VLA-1 (CD49a/CD29), VLA-2 (CD49b/CD29), VLA-3 (CD49c/CD29), VLA-4 (CD49d/CD29), VLA-5 (CD49e/CD29) and VLA-6 (CD49f/CD29) proteins. A second group shares the .beta.2 unit (CD18), and typically functions in cell to cell interactions. This second group includes LFA-1 (CD18/CD11a), MAC-1 (CD18/CD11b), and p150,95 (CD18/CD11c). The LFA-1.alpha. unit (CD11a protein, i.e., Sequence ID No. 2) is the specific heterodimer counterpart to the .beta.2 unit in LFA-1.
Li et al., A Leukocyte Integrin Binding Peptide from Intercellular Adhesion Molecule-2 Stimulates T Cell Adhesion and Natural Killer Cell Activity, 268 J. Biol. Chem. 21474-21477 (Jul. 20, 1993), report that .beta.2 integrins, and particularly LFA-1, have a cytoplasmic domain which serves to alter protein configuration via a cellular phosphorylation pathway communicating the integrin and respective cell receptor areas. That is to say, phosphorylation may be activated at a remote receptor site with the result of indirectly inducing conformational changes in the integrin via cytoplasmic phosphorylation.
On the other hand, ICAM-1 proteins are not known to incur phosphorylation induced conformational changes. ICAM-1 is found primarily upon monocytes and endothelial cells, and is widely inducible, or upregulated, on many cells including B and T lymphocytes, thymocytes, dendritic cells, endothelial cells, fibroblasts, keratinocytes, chondrocytes, and epithelial cells. This protein has a co-stimulatory effect upon cytotoxic T-cell interaction, and is utilized in a number of intercellular binding interactions.
Recent developments in the field of protein chemistry confirm that short-chain peptides, which have amino acid residue sequences representing mere fragments of a corresponding parent protein molecule, may exhibit significant levels of biofunctionality. Short-chain peptides that derive from the ICAM-1 protein are known to have utility in blocking binding interactions between cells and viruses. Even so, only a very limited number of specific ICAM-1 based peptides have been shown to be useful.
European Patent Publication No. EP 391,088 A2 indicates that functional derivatives of the intercellular adhesion molecule ("ICAM-1") may be used in anti-viral therapy. These functional derivatives may include functional domains and fragments of the ICAM-1 molecule. The method of using these fragments includes administering them in a manner that prevents viral infection of potential viral host cells by impairing a binding interaction between the cells and rhinoviruses that may contact the cells. The binding interaction to be impaired includes one between an ICAM-1 cellular receptor and a corresponding viral adhesion site. The ICAM-1 fragments impair the cell-to-virus binding interaction by competing with normal cellular ICAM-1 molecules for adhesion to the corresponding viral binding site.
Another publication, PCT/AU91/00205, describes the use of short-chain ICAM-1 based peptides for inhibiting intercellular adhesion in mammals.

ICAM-1/LFA-1 short-chain peptides and method of using same


Apparatus and method of providing an estimate of a transmit sequence from a receive sequence. The transmit sequence includes transmit sequence values. The transmit sequence value is transmittable by one of a group of transmitting points through a communication channel of a plurality of communication channels to a receiving point. The communication channel extends from a transmitting point to a receiving point. The receive sequence includes an interference of transmit sequence values.

1. Field of the Invention
The present invention is in the field of telecommunications and, in particular, in the field of equalization in a multiple input scenario, in which a receiver receives signals from more than one transmit antenna.
2. Description of Related Art
The steadily-increasing demand for high data rates necessary for todays and future mobile radio applications requires high data rate transmission techniques efficiently exploiting the available bandwidth or, in other words, the achievable channel capacity. Therefore, multiple input multiple output (MIMO) transmission systems have achieved considerable importance in recent years. MIMO systems employ a plurality of transmitting points, each of the transmitting points having a transmit antenna, and a plurality of receiving points, each of the receiving points having a receiving antenna, for receiving signals being transmitted by the multiple transmitting points through different communication channels.
For example, an enormous capacity increase can be achieved on a multiple input multiple output channel in rich scattering environments. The capacity increase is linear with a number of transmit antennas unless it exceeds a number of receive antennas. In order to enable highly reliable communications in such a system, maximum-likelihood detection would be the optimum way, however, as the number of transmit antennas increases, the complexity of the receiver becomes prohibitive.
The increasing receiver complexity with increasing number of transmit antennas results from an increasing number of communication channels to be taken into account in order to detect the information transmitted by the number of transmit antennas from a signal received by a further number of receive antennas. In P. W. Wolniansky, G. J. Foschini, G. D. Golden and R. A. Valenzuela, "V-Blast: An Architecture for Realizing Very High Data Rates Over the Rich-Scattering Wireless Channel", in URSI International Symposium on Signals, Systems, and Electronics, September 1998, pp. 295-300, a vertical bell labs layered space-time (V-Blast) detection scheme with lower complexity is disclosed. Independent data streams associated with different transmit antennas, called layers, are detected at a receiver by nulling out interference of other layers from each other in a successive manner.
Moreover, it was suggested, to perform an optimum detection ordering which is of great importance for the successive interference cancellation, whereby, at each detection stage, a transmit signal value estimate associated with a smallest estimation error is provided.
The V-Blast detection scheme mentioned above calculates the nulling vector based on a zero forcing (ZF) criterion. S. Böro, G. Bauch, A. Pavlic, and A. Semmerl. "Improving BLAST Performance using Space-Time Block Codes and Turbo Decoding," in Proc. IEEE Global Telecommunications Conference (GLOBECOM 2000), vol. 2, November/December 2000, pp. 1067-1071 and A. Benjebbour, H. Murata, and S. Yoshida. "Comparison of Ordered Successive Receivers for Space-Time Transmissions," in Proc. IEEE Vehicular Technology Conference (VTC 2001-Fall), Atlantic City, USA, October 2001, pp. 2053-2057, disclose detection schemes where a minimum mean square error (MMSE) criterion is adapted to the V-Blast architecture improving the performance. These detection schemes require calculation of either pseudo inverse (ZF V-Blast) or inverse (MMSE V-Blast) of a matrix at each detection stage, i.e., at every step of layer detection, which is still computationally expensive and prohibitive for large number of data streams. Therefore, the estimation complexity associated with the above-mentioned detection schemes is enormous.
For the ZF criterion, a reduction of complexity is possible. In D. Wübben, R. Böhnke, J. Rinas, V. Kühn and K. D. Kammeyer, "Efficient Algorithm for Decoding Layered Space-Time Codes," IEE Electronics Letters, vol. 37, no. 22, pp. 1348-1350, October 2001 and in D. Wübben, J. Rinas, R. Böhnke, V. Kühn and K. D. Kammeyer, "Efficient Algorithm for Decoding Layered Space-Time Codes," in Proc. Of 4. ITG Conference on Source and Channel Coding, Berlin, January 2002, pp. 399-405, computational reduction schemes are proposed which are based on QR decomposition with suboptimum detection ordering.
In W. Zha and S. D. Blostein, "Modified Decorrelating Decision-Feedback Detection of BLAST Space-Time System," in Proc. IEEE Int. Conference on Communications (ICC 2002), vol. 1, New York, USA, April/May 2002, pp. 335-339 discloses a Cholesky factorization which is utilized with reordering by unitary transformation at every detection stage leading to optimum ordering.
A similar contribution based on QR decomposition for MMSE criterion is disclosed in R. Böhnke, D. Wübben, V. Kühn, and K. D. Kammeyer, "Reduced Complexity MMSE Detection for BLAST Architecture," in Proc. IEEE Global Telecommunications Conference (GLOBECOM 2003), vol. 4, San Francisco, USA, December 2003, pp. 2258-2262. The ordering disclosed therein is suboptimum which leads to an increased detection error.
In B. Hassibi, "An Efficient Square-Root Algorithm for BLAST," in Proc. IEEE Int. Conference on Acoustics, Speech, and Signal Processing. (ICASSP'00), vol. 2, Istanbul, June 2000, pp. II737-II740, a unitary transformation is disclosed for reordering. In E. Biglieri, G. Taricco and A. Tulino, "Decoding Space-Time Codes With BLAST Architectures," IEEE Transactions on Signal Processing, vol. 50, no. 10, pp. 2547-2552, October 2002, a Cholesky factorization is disclosed which, however, does not involve an ordering strategy and, therefore, does not lead to an optimum performance.
In other words, the prior art approaches disclose either a reduction of complexity associated with a suboptimum detection ordering, which leads to an increased estimation error, or an optimum reordering for reduction of the estimation error at a cost of an increased complexity.
FIG. 10 shows a system model of MIMO channel. The system is equipped with NT transmit antennas and NR receive antennas, where NT≦NR. In the following, it is assumed, that the signals are narrow band so that a non-dispersive fading channel is present. Moreover, FIG. 10 shows a discrete time system model in an equivalent complex baseband.
The channel inputs xi, i=1, . . . , NT are complex valued baseband signals and are transmitted from NT antennas simultaneously. In other words, each transmit antenna transmits a channel input value of the channel input sequence. The channel tap gain from transmit antennas i to receive antenna j is denoted by hj,i.
These channel taps are independent zero mean complex Gaussian variables of equal variance E[|hj,i|2]=1. This assumption of independent paths holds if antenna spacing is sufficiently large and if the system is surrounded by rich scattering environment. The signal at receive antenna j can be expressed by
            y      j        =                            ∑                      i            =            1                                N            T                                                        h                          j              ,              i                                                      x            i                              +              n        j              ,where y=Hx+n is an additive noise at receive antenna j. By collecting the receive signal values determined by the above equation for NR receive antennas, the receive signals can be concisely expressed in matrix formy=Hx+njwhere
      H    =          [                                                  h                              1                ,                1                                                          ⋯                                              h                              1                ,                                  N                  T                                                                                ⋮                                ⋰                                ⋮                                                              h                                                N                  R                                ,                1                                                          ⋯                                              h                                                N                  R                                ,                                  N                  T                                                                        ]        ,y=[y1, . . . , yNR]T, x=[x1, . . . , xNT]T, n=[n1, . . . , nNR]T, and (•)T denotes transposition.
FIG. 11 demonstrates a detection procedure of V-Blast. The receive signal y=y1, which is a vector, is filtered by a filter with coefficients fk1H to estimate the k1-th data stream which is the most reliable estimate among all NT entries of x, i.e., with minimum MSE at this first stage. The output is quantized by Q(•) and decision is made on xk1. Assuming that this decision is correct ({circumflex over (x)}k1=xk1), contribution of xk1 on the receive signal y1 is subtracted by multiplying xk1 with the corresponding channel impulse response hk1, which is a vector, which is the k1-th column of H. This procedure is repeated NT times until all the entries of x are detected.
In the following, a detailed filter calculation and ordering strategy according to the above prior art approach will be described.
An error signal of a linear filter FH is expressed asε=FHy−x.
The linear MMSE filter can be found by applying an orthogonality by principle, i.e., E[εyH]=0. From the above equations, a solution is given byFH=ΦxxHH(HΦxxHH+Φnn)−1,where covariance matrices of channel input and noise are defined asΦxx=E[xxH]undΦnn=E[nnH].
Assuming that the covariance matrices in the above equation are invertible, the above equation for the linear filter may be represented in an alternative form
      F    H    =                    (                              Φ            xx                          -              1                                +                      H                                                                                Φ              nn                              -                1                                                                H              H                                      )                    -        1                        H      H                  Φ      nn              -        1            where the known matrix inversion lemma has twice been applied to obtain the above equation. From the above, the error covariance matrix reads as
      Φ    εε    =            E                    [                              ∈∈                    H                ]              =                            (                                    Φ              xx                              -                01                                      +                                          H                H                                                          Φ                nn                                  -                  1                                                          H                                )                          -          1                    .
It is to be noted that the diagonal entries of Φεε are MSE, i.e., E[|xi−{circumflex over (x)}i|2], i=1, . . . , NT. Thus, the k1-th data stream having the minimum diagonal entry of Φεε can be seen as the most reliable one in the MMSE sense and must be detected at the first stage in order to avoid error propagation, which corresponds to the optimum ordering mentioned above.
The corresponding filter fk1H corresponds to the k1-th row of FH. At the second stage, since k1-th entry of x has been detected, the k1-th column of the channel matrix H can be neglected, leading to an updated system only with NT−1 transmit antennas.
In order to generalize the procedure, a deflated channel matrix H(i) is introduced where columns k1, . . . , ki−1 of H are replaced by zeros for i=2, . . . , NT and H(1)Δ=H. At i-th stage, Φεε(i) and F(i),H are calculated from the above equations by replacing H with H(i). Then, the optimum detection scheme can be described as
            k      i        =                  argmin                  k          ∉                      {                                          k                i                            ,                                                                        …                                                                        ,                              k                                  i                  -                  1                                                      }                                            e        k        T                          Φ                  ∈          ∈                          (          i          )                                  e        k                                f                  k          i                H            =                                    e                          k              i                        T                                          F                                          (                i                )                            ,              H                                      =                              e                          k              i                        T                                          Φ                          ∈              ∈                                      (              i              )                                                      H            H                                          Φ            nn                          -              1                                            ,  where ek is the k-th column of an identity matrix of size NT and the last step follows from the equations mentioned above. Therefore, MMSE-V-Blast repeats the procedure and requires matrix inverse calculations NT times for each receive sequence, which is computationally expensive. In other words, the above-discussed detection scheme applies an optimum ordering, so that a resulting estimation error is reduced. This error reduction is however, associated with an enormous computational complexity.
In E. Bigliei, g. Taricco and A. Tulino, "Decoding Space-Time Codes With BLAST Architectures," IEEE Transactions on Signal Processing, vol. 50, no. 10, pp. 2547-2552, October 2002, and in G. Ginis and J. M. Cioffi, "On the Relation Between V-BLAST and the GDFE," IEEE Communications Letters, vol. 5, no. 9, pp. 364-366, September 2001, the V-Blast architecture is described by a pair of forward and backward block filters with certain constraint on the backward filter structure. A resulting block diagram is shown in FIG. 12.
The sequence estimator shown in FIG. 12 comprises a forward filter 1201 having a number of inputs corresponding to a number of receive antennas, and a number of outputs coupled to a subtractor 1203. The subtractor 1203 has a number of outputs 1205 and a number of further inputs 1207. In other words, the filter 1201 is the previously mentioned forward filter. The number of outputs 1205 of the subtractor 1203 is coupled to a quantizer 1209 being operative for performing a hard decision. The quantizer has a number of outputs 1211 corresponding to the number of transmit antennas (or number of channel inputs). The number of outputs 1211 is fed back to a backward filter 1213 having a number of outputs corresponding to the number of receive antennas. The number of outputs of the backward filter 1213 is coupled to the number of further inputs 1207 of the subtractor 1203.
The estimate of a transmit sequence is provided via the number of outputs 1211 of the quantizer 1209. The estimates detected by the quantizer 1209 are filtered by the backward filter 1213, and filtered detected estimates are subtracted from filtered values provided by the forward filter 1201 in order to reduce intersymbol interferences. Therefore, the structure shown in FIG. 12 can be considered as a decision-feedback equalizer (DFE) structure, which is equivalent to the structure of FIG. 11.
The feedback filter BH must be unit lower (or upper) triangular so that the outputs of BH−1 are not subtracted from already detected signals. This is the causality constraint which is necessary to describe the successive interference cancellation procedure properly. In this context, a unit lower (upper) triangular matrix is a lower (upper) triangular matrix with one ("1") values along the main diagonal.
However, the above-discussed approach suffers from the disadvantage, that there is no concern about detection ordering. In other words, the approach shown in FIG. 12 assumes that the detection ordering is already optimum, which is not the case all the time. Although the detection scheme associated with the structure shown in FIG. 12 has reduced complexity with respect to the estimation scheme of FIG. 11, it suffers from an increased estimation error in a case of a non-optimum decision ordering, i.e., in the case when the input sequence values are not reordered in such a way that the decision ordering is optimum.

Apparatus and method for providing an estimate of a transmit sequence


A process for the recovery of C.sub.2 components (ethylene and/or ethane) and heavier hydrocarbon components from a gas stream containing a significant quantity of components more volatile than methane (e.g., hydrogen, nitrogen, and/or others) is disclosed. The cooled, partially condensed hydrocarbon bearing gas stream is separated into a vapor containing substantial quantities of the component(s) more volatile than methane and a liquid containing predominantly hydrocarbons. The vapor is expanded to the distillation column pressure and then supplied to the column at an upper mid-column feed position. The liquid is expanded to column pressure and supplied to the column at a lower mid-column feed position. A recycle stream is withdrawn from the column at a point below the upper mid-column feed position where the bulk of the volatile components are supplied to the column. The recycle stream is compressed and cooled so that a substantial portion is condensed and then supplied to the column as reflux at the top column feed position. The major portion of this reflux is liquid methane which allows the recovery of a significant portion of the C.sub.2 and heavier components that are in the vapors in the upper section of the distillation column. The distillation column overhead vapor contains predominantly methane and the more volatile components The major portion of the desired components is recovered in the distillation column bottom liquid product.

This invention provides an improved process for separating a hydrocarbon bearing gas stream containing significant quantities of components more volatile than methane (e.g., hydrogen, nitrogen, etc.) into two fractions: one fraction contains predominantly methane and the more volatile components and the second fraction contains the recovered desirable ethylene/ethane and heavier hydrocarbons components.
Ethylene/ethane, propylene/propane and heavier hydrocarbons can be recovered from a variety of gases, such as natural gas, refinery gas and synthetic gas streams obtained from other hydrocarbon materials such as coal, crude oil, naphtha, oil shale, tar sands and lignite. Hydrocarbon bearing gas typically contains components more volatile than methane (e.g., hydrogen, nitrogen, etc.) and often unsaturated hydrocarbons (e.g., ethylene, propylene, etc.) in addition to methane, ethane and hydrocarbons of higher molecular weight such as propane, butane and pentane. Sulfur-containing gases and carbon dioxide are also sometimes present. The present invention is generally concerned with the recovery of ethylene/ethane and heavier (C.sub.2 +) hydrocarbons from such gas streams.
Recent changes in ethylene demand have created increased markets for ethylene and derivative products. In addition, fluctuations in the prices of both natural gas and its NGL constituents have increased the incremental value of ethane and heavier components as liquid products. These market conditions have resulted in a demand for processes which can provide high ethylene recovery and more efficient recoveries of all these products. Available processes for separating these materials include those based upon cooling and refrigeration of gas, oil absorption and refrigerated oil absorption. Additionally, cryogenic processes have become popular because of the availability of economical equipment which produces power while simultaneously expanding and extracting heat from the gas being processed. Depending upon the pressure of the gas source, the richness (C.sub.2 + content) of the gas and the desired end products, each of these processes or a combination thereof may be employed.
The cryogenic expansion process is now generally preferred for ethylene/ethane recovery because it provides maximum simplicity with ease of start up, operating flexibility, good efficiency, safety and good reliability. U.S. Pat. Nos. 4,061,481, 4,157,904, 4,171,964, 4,27S,457 and 4,617,039 describe relevant processes.
In a typical cryogenic expansion recovery process, a feed gas stream under pressure is cooled by heat exchange with other streams of the process and/or external sources of refrigeration such as a propane compression-refrigeration system. As the gas is cooled, liquids may be condensed and collected in one or more separators as high-pressure liquids containing some of the desired C.sub.2 + components. Depending on the richness of the gas and the amount of liquid formed, the high-pressure liquids may be expanded to a lower pressure and fractionated. The vaporization occurring during expansion of the liquid results in further cooling of the stream. Under some conditions, pre-cooling the high pressure liquid prior to the expansion may be desirable in order to further lower the temperature resulting from the expansion. The expanded stream, comprising a mixture of liquid and vapor, is fractionated in a distillation (demethanizer) column.
If the feed gas is not totally condensed (typically it is not), the vapor remaining from the partial condensation is passed through a work expansion machine or engine, or an expansion valve, to a lower pressure at which additional liquids are condensed as a result of further cooling of the stream. The pressure after expansion is usually the same as the pressure at which the distillation column is operated. The combined vapor-liquid phases resulting from the expansion are supplied as feed to the column.
In the column, the expansion-cooled stream(s) is (are) distilled to separate residual methane, nitrogen, and other volatile gases as overhead vapor from the desired ethylene/ethane, propylene/propane and heavier components as bottom liquid product.
In the ideal operation of such a separation process, the residue gas leaving the process will contain substantially all of the methane and more volatile components in the feed gas with essentially none of the heavier hydrocarbon components and the bottoms fraction leaving the demethanizer will contain substantially all of the heavier components with essentially no methane or more volatile components. In practice, however, this ideal situation is not obtained for the reason that the conventional demethanizer is operated largely as a stripping column. The residue gas from the process, therefore, typically comprises vapors leaving the top fractionation stage of the column, together with vapors not subjected to any rectification step. Considerable losses of ethylene/ethane (C.sub.2) occur because the top liquid feed contains substantial quantities of C.sub.2 + components, resulting in
corresponding equilibrium quantities of C.sub.2 + components in the vapors leaving the top fractionation stage of the demethanizer. This problem is exacerbated if the gas stream(s) being processed contain relatively large quantities of components more volatile than methane (e.g., nitrogen, hydrogen, etc.), because the volatile vapors rising up the column strip C.sub.2 + components from the liquids flowing downward. The loss of the desirable C.sub.2 + components could be significantly reduced if the rising vapors could be brought into contact with a significant quantity of liquid (reflux), containing very little C.sub.2 + components; that is, reflux capable of absorbing the C.sub.2 + components from the vapors. The present invention provides the means for achieving this objective and significantly improving the recovery of the desired products.
In accordance with the present invention, it has been found that ethylene recoveries in excess of 99 percent can be obtained. In addition, the present invention makes possible higher ethylene and ethane recoveries (up to several percentage points higher) than prior art processes with the same energy requirements. The present invention is particularly advantageous when processing feed gas that contains more than 10 mole % of components more volatile than methane (e.g., hydrogen, nitrogen, etc.).


A server for campaign optimization is described. An experience content dataset is generated for an augmented reality application of a device based on analytics results. The analytics results are generated based on analytics data received from the device. The experience content dataset is provided to the device. The device recognizes a content identifier of the experience content dataset and generates an interactive experience with a presentation of virtual object content that is associated with the content identifier.

A device can be used to generate additional data based on an image captured with the device. For example, augmented reality (AR) is a live, direct or indirect, view of a physical, real-world environment whose elements are augmented by computer-generated sensory input such as sound, video, graphics or GPS data. With the help of advanced AR technology (e.g. adding computer vision and object recognition) the information about the surrounding real world of the user becomes interactive. Artificial information about the environment and its objects can be overlaid on the real world.

Campaign optimization for experience content dataset


A threaded joint for steel pipes comprising a pin (1) and a box (2). The pin has a male thread (11) and a lip (12) which comprises (i) a sealing surface (13) and (ii) a nose portion (16) provided with a shoulder surface. The box has a female thread (21), a sealing surface (23) and a shoulder surface. The shoulder surface of the pin comprises two distinct adjacent surfaces, main shoulder (14) in the inner side and sub shoulder (15) in the outer side. Correspondingly, the shoulder surface of the box comprises two distinct adjacent surfaces, main shoulder (24) in the inner side and sub shoulder (25) in the outer side. The main shoulder surfaces of the pin and box are disposed such as to prevent a radially inward deformation of the lip end, and the sub shoulder surfaces of pin and box are disposed such as to limit a radially outward deformation of the lip end. The main shoulder of the pin has a greater radial dimension than said sub shoulder of the pin, and at least the main shoulder surface of the pin is in axial abutment with at least the corresponding main shoulder surface of the box.

Technology used for connecting steel pipes used in equipment of the oil production industry such as oil country tubular goods, riser pipes, and line pipes includes threaded joints. Threaded joints for steel pipes are constituted by a pin having a male thread element provided at the end of a first tubular member and a box which is a female thread element provided at the end of a second tubular member. The joint is tightened by engaging the male thread and the female thread.
Standard threaded joints are prescribed by API (American Petroleum Institute) standards but in recent years, the environments for exploration and production of crude oil and natural gas are becoming more severe. As a result, there is increasing use of high performance special joints referred to as premium joints which are not prescribed by API standards.
In a typical premium joint, in addition to a tapered thread for firmly connecting steel pipes, the pin and the box have sealing surfaces which can form a metal-to-metal seal for providing sealing performance and torque shoulder surfaces for acting as stoppers during tightening (make-up).
In the past, since vertical wells were predominant, it was sufficient for a threaded joint for OCTG to resist the tensile load due to the weight of pipes and to prevent leakage of high pressure fluid passing through it. However, in recent years, wells are becoming deeper, and deviated wells and horizontal wells which bend underground are increasing, and the development of wells in difficult environments such as in the sea or in polar regions is increasing. Therefore, the properties required for threaded joints are becoming more varied and more strict as exemplified by resistance to compression, resistance to bending, ability to seal against external pressure, and ease of use in the field.
As a result, qualification tests for threaded joints are becoming more severe. In the Series A test of recent ISO 13679 standards; alternances of internal pressure and external pressure combined with tension or compression (internal pressure+tension, internal pressure+compression, external pressure+tension, and external pressure+compression) (herein referred to as repeated combined loads) are applied three times. Such severe test conditions were not taken into consideration in the past in the development of threaded joints.
As shown in FIG. 2, a typical premium joint has a structure in which an unthreaded portion 12 referred to as a lip portion is provided at the end of a threaded portion having a tapered male thread 11 provided on a pin 1 which is a male threaded element. A sealing surface 13 for forming a metal-to-metal seal is provided on the outer peripheral surface of the lip portion. A torque shoulder surface 14 is provided on the end surface of the lip portion (and accordingly on the end surface of the pin).
Naturally, a box 2 which is a corresponding female threaded element is provided with a female thread 21, a sealing surface 23, and a shoulder surface 24 at the rear of the box which correspond to or mate with the male thread 11, the sealing surface 13, and the end surface shoulder surface 14, respectively, of the pin 1.
An overlap in the radial direction referred to as interference is provided between the sealing surfaces of the pin and the box. This type of threaded joint is designed so that if the joint is tightened until the shoulder surfaces of the pin and the box contact each other, the sealing surfaces of both members are in intimate contact around their entire periphery and sealing is provided by metal-to-metal contact.
The above-described sealing performance is exhibited to the highest degree when tightening is carried out with a suitable torque in the period from when the shoulders abut until the shoulders begin to undergo plastic deformation (when a normal tightened state occurs).
The shoulder surfaces act not only as stoppers for tightening but also act to bear almost all of a compressive load acting on the joint. Therefore, if the shoulder surfaces are not thick or if the shoulders are not stiff, they cannot withstand a large compressive load.
Prior art for increasing the resistance to external pressure and resistance to compression of a premium joint is described in WO 2004/109173 (Patent Document 1). That threaded joint greatly increases resistance to external pressure by providing a portion which does not contact the box (referred to below as a nose portion) between the shoulder surface and the sealing surface of the end surface of the pin. At the same time, the taper angle of the nose portion is made 0 degrees (a cylindrical surface) or is made smaller than that of the sealing surface. Due to the provision of the nose portion, a decrease in the thickness of the end surface shoulder surface is prevented, and an increase in resistance to compression can be achieved.
However, in the threaded joint described in Patent Document 1, when a high compressive force and external pressure are simultaneously applied, and when a tensile force and internal pressure are subsequently simultaneously applied, it has been found by the inventors that there can be a risk of developing a leak.
WO 00/08367 (Patent Document 2) discloses a threaded joint in which a tight contacting region is provided in two locations of a lip portion, namely, a tight contacting region near the threaded portion is defined as a sealing surface and a tight contacting region near the end surface (shoulder surface) is defined as a protecting portion. The protecting portion which is a second contact region provided in a location close to the end of the lip portion has the object of supplying a first seal to internal pressure (and thus to protect the sealing surface) and to optimize the forces and moments undergone by the lip.
In the threaded joint described in Patent Document 2, the amount of interference of the protecting portion is set to be higher than the amount of interference of the sealing surface (at least 1.15 times and at most 1.3 times) in order to retain a sufficient amount of contact pressure on the protective portion while a moderate contact pressure is obtained on the sealing surface. In addition, as Patent Document 2 incites to set sufficient distances from the shoulder to the protective portion, from the protective portion to the sealing surface and from the sealing surface to the thread, the lip portion is designed to be extremely long, so a sufficient thickness (radial dimension) of the shoulder surface may not be obtained. As a result, when a high compressive load is applied, the joint may not sufficiently withstand the compressive load, and it is thought that its compressive performance may be inadequate.
DE 4446806 (Patent Document 3) discloses a threaded joint of the same type as disclosed in Patent Document 2.
U.S. Pat. No. 4,473,245 (Patent Document 4) discloses a threaded joint in which a metal-to-metal seal is provided on the exterior of the pipe and a torque shoulder provides an additional metal-to-metal seal. In the threaded joint disclosed in Patent Document 4, however, the thickness of a lip portion is designed to be very thin, so it is difficult to ensure the resistance to high external pressure and high compression.
U.S. Pat. No. 3,489,437 (Patent Document 5) discloses a threaded joint in which a metal-to-metal seal and a shoulder are provided. However, in the threaded joint disclosed in Patent Document 5, the lip portion is designed according to the same rule as a typical premium joint in FIG. 2, so it is not considered to ensure the resistance to high external pressure and high compression.
U.S. Pat. No. 3,870,351 (Patent Document 6) discloses a threaded joint characterized by its shoulder surfaces having a particular profile. In the threaded joint disclosed in Patent Document 6, the shoulder surfaces are rounded profiles (the shoulder surface of one of the pin and box being convex and that of the other being concave), and they function to form a second seal. This structure is intended to equalize the contact between the sealing surfaces of the first seal by suppressing misalignment or the flexure of the lip toward the pipe axis at the time of make-up.
However, in a threaded joint disclosed in Patent Document 6, although equalization of the sealing contact or sealing pressure of the first seal is taken into account, it is out of consideration to use the threaded joint in a situation where a high compression force and high external pressure simultaneously act thereon. As shown in FIG. 7 of this patent document, there is a space between the outer side of the concave shoulder surface of the box and the outer edge of the convex shoulder surface of the pin. In a situation where a high tension force and high external pressure act thereon, the shoulder surfaces of pin and box can separate easily due to the high tensional force and the tip of lip can easily be deformed or be moved towards the outer side (that is, in the direction which expands the diameter). Therefore, in a threaded joint disclosed in Patent Document 6, it is difficult to control and suppress the deformation or movement of the tip of the pin towards the outer side as described above. Furthermore, if the shoulder surface of the pin has a convex profile, the innermost edge part of the shoulder surface of the box which is concave is so thin that the shoulder surface of the box tends to undergo a heavy plastic deformation when a high compression load is applied to the joint.
Patent Document 1: WO 2004/109173
Patent Document 2: WO 00/08367
Patent Document 3: DE 4446806
Patent Document 4: U.S. Pat. No. 4,473,245
Patent Document 5: U.S. Pat. No. 3,489,437
Patent Document 6: U.S. Pat. No. 3,870,351

NIPPON STEEL & SUMITOMO METAL CORPORATION


A method of monitoring relative nerve health and the presence of neuropraxia is described. The methods utilize the integration of a waveform function of an elicited or monitored nerve response to provide an indication of the strength of a detected signal from a nerve and thus the relative health and integrity of the nerve. In some embodiments motor nerve stimulation innervates muscle and an EMG waveform is obtained in response thereto. The integration under the waveform is expressed and an indexed value indicating a percentage of a certain threshold value. Methods set forth provide a more reliable status of a nerve in real-time and allow action to be taken to reduce neuropraxia or prevent permanent nerve damage.

Field of the Invention
The present invention relates generally to methods for the monitoring of nerves and specifically to the detection of reversible nerve injury.
Description of the Related Art
Reversible Nerve Injury, known as "neuropraxia," is a medical condition where a motor nerve is stressed, often occurring during surgery, by surgical trauma, stretching, and/or devascularization. Because neuropraxia is preventable, it is of value to identify degrees of neuropraxia early and to quantify the extent of nerve injury. An insult capable of causing neuropraxia may be capable of resulting in irreversible nerve palsy. This is an additional concern and reason for detecting and preventing neuropraxia.
Historically, neuropraxia prevention was attempted by Intraoperative Nerve Monitoring (IONM). This technique involved collection of electromyographic responses (EMG) from the target muscle innervated by target nerves and "monitoring" those responses for waveform patterns typical of irritation of the nerve. IONM response might include sustained EMG activity due to stretch or tension on the nerve from retraction. IONM EMG response of significance might also include bursts of activity associated with a dissection recognized as being risky by the surgeon (surgeon identified response) or activity which is seen by an individual monitoring the IONM equipment, such as visual or auditory feedback from the EMG.
A relatively new modality of neuropraxia detection is the observation of evoked responses of the nerve. In this method, a nerve response is "evoked" by an electronic nerve stimulator and the response is examined for indications of the functional integrity of the stimulated nerve. Indications might include latency of response (the time from the stimulation to the onset of the evoked response), the morphology of the response waveform, and the amplitude of the evoked response voltage. This type of testing can be automatic by "ping" testing with an implantable stimulator probe, or manually by the surgeon using a hand held stimulation probe. FIG. 1 depicts an example of a waveform 100 of an evoked EMG response 102 wherein the response plotted on a graph wherein the y-axis 104 represents electric response output and the x-axis 106 represents time. Prior art methods observe changes in the amplitude (peak-to-peak) values 108 or differentiation (i.e. the slope of the waveform) to infer the onset of neuropraxia. However, this is not a completely accurate representation of the strength of a nerve response or the integrity of the monitored nerve.
Present methods of Neuropraxia detection, especially those requiring implantation of dedicated stimulation devices and those relating to voltage response algorithms may be costly, time consuming, suffer from lack of reliability, and counter-intuitive in conceptualization, possibly leading to misdiagnosis during the stress of performing live surgery. In addition, voltage responses do not always truly reflect the degree of injury to a nerve, the response also being dependent on the strength of stimulation, the size and excitability of the target muscle, and the effectiveness of the pickup electrodes. Of particular disadvantage is the fact that nerve response can occur without actual muscle movement, giving a false negative indication of advancing neuropraxia. A more reliable and efficient method for monitoring the heath and response strength of a nerve is therefore needed.

Method of detecting reversible nerve injury


A module for generating ions in a flowing air stream includes a support structure having a central region adapted to pass a flowing air stream therethrough, and including a plurality of supports for positioning a filamentary ion-generating electrode in a polygonal configuration within the central region. The supports and filament are relatively moveable to wipe the surface of the filament at each support for removing accumulated contaminants on the filament.

Air ionizers that use gas, such an air, to disperse ions typically operate by moving the gas past ionizing electrodes that produce ions due to corona discharge in response to high ionizing voltage applied to the electrodes.
The moving gas disperses ions in a flowing stream toward objects to be charged or discharged. Particles, usually present in air, accumulate on a highly-charged surface of ionizing electrodes, thus reducing ion output and changing a balance between generated positive and negative ions produced by the ionizing electrodes.
Conventional methods and apparatuses for cleaning pointed or needle-like ionizing electrodes commonly include manually operated brushes that sweep tips of ionizing electrodes and dislodge accumulated particles. Alternatively, brushes installed on a rotating hub of a fan that produces the flow of gas relies upon centrifugal force to move the brushes in and out of contact with ionizing electrodes to dislodge accumulated particles.
In ionizers having an ionizing electrode formed as a thin wire (filament), the ionizing electrode also attracts particles and requires periodic cleaning. Such filament can also be cleaned manually as by brushing but over a substantially larger area than for ionizers with emitter points. And, areas next to supports for a filament cannot be sufficiently cleaned by a rotating brush.


A turbine blade for a turbine engine having an internal cooling system formed from a plurality of cooling chambers extending radially in the blade and configured to create vortices within the chambers. In at least one embodiment, the cooling system may be formed from leading edge cooling chambers, trailing edge cooling chambers, suction side mid-chord cooling chambers, and pressure side mid-chord cooling chambers that are configured to receive cooling fluids from supply channels in a root of the blade and to create vortices in the cooling chambers. The vortices of cooling fluids increase heat removal from the turbine blade. The cooling fluids may be exhausted from the turbine blade through film cooling orifices.

Typically, gas turbine engines include a compressor for compressing air, a combustor for mixing the compressed air with fuel and igniting the mixture, and a turbine blade assembly for producing power. Combustors often operate at high temperatures that may exceed 2,500 degrees Fahrenheit. Typical turbine combustor configurations expose turbine blade assemblies to these high temperatures. As a result, turbine blades must be made of materials capable of withstanding such high temperatures. In addition, turbine blades often contain cooling systems for prolonging the life of the blades and reducing the likelihood of failure as a result of excessive temperatures.
Typically, turbine blades, as shown in FIG. 1, are formed from a root portion and a platform at one end and an elongated portion forming a blade that extends outwardly from the platform. The blade is ordinarily composed of a tip opposite the root section, a leading edge, and a trailing edge. The inner aspects of most turbine blades typically contain an intricate maze of cooling channels forming a cooling system. The cooling channels in the blades receive air from the compressor of the turbine engine and pass the air through the blade. The cooling channels often include multiple flow paths that are designed to maintain all aspects of the turbine blade at a relatively uniform temperature. However, centrifugal forces and air flow at boundary layers often prevent some areas of the turbine blade from being adequately cooled, which results in the formation of localized hot spots. Localized hot spots, depending on their location, can reduce the useful life of a turbine blade and can damage a turbine blade to an extent necessitating replacement of the blade.
Conventional turbine blades have many different designs of internal cooling systems. Many of the cooling systems include channels for passing cooling fluids through a plurality of cooling channels before exhausting the fluids through film cooling holes. While many of these conventional systems have operated successfully, the cooling demands of turbine engines produced today have increased and outgrown the cooling capacities of these conventional systems. Thus, an internal cooling system having increased cooling capabilities is needed.

Vortex cooling system for a turbine blade


A method for manufacturing a semiconductor device may comprise forming a conductive layer on a substrate, removing at least one portion of the conductive layer to form a plurality of separate conductive lines, forming a first stress-inducing layer of a first stress type on the conductive lines and the substrate, and removing a portion of the first stress-inducing layer such that a remaining portion of the first stress-inducing layer is disposed on a first subset of the conductive lines but not a second subset of the conductive lines and has a boundary disposed between two of the conductive lines. This method, along with other methods and various semiconductor devices, are described.

Many semiconductor devices incorporate a dual-stress liner that blankets the various transistors of the devices and enhances their performance. In a dual-stress liner, a compressive stress liner is disposed over a region containing P-type field-effect transistors (PFETs) such that a compressive stress is induced on the PFET channels, and a tensile stress liner is disposed over a region containing N-type field-effect transistors (NFETs) such that a tensile stress is induced on the NFET channels. Thus, at least one boundary exists between the compressive and tensile stress liners.
There are various issues that should be dealt with when incorporating a dual-stress liner. For instance, at the boundary, the compressive and tensile stress liners may either overlap each other or there may be a gap between the two liners. Exact butting together of the two liners is neither a reliably repeatable nor practical structure to manufacture.
If the boundary has a gap between the two liners, then etching during manufacturing of through-holes in the stress liners intended for conductive contacts may also undesirably etch underlying silicide and silicon layers through the gap.
On the other hand, where the boundary is an overlapping boundary, then difficulties arise in simultaneously etching both the double-thickness overlap region and the single-thickness non-overlap regions of the stress layers. To effectively etch holes through the double layer thickness region, over-etching will typically occur in the single layer thickness regions. This over-etching may damage the device and reduce the yield of operational devices in a given batch. Moreover, since the majority of contacts are located in the single-layer thickness regions of the stress liners, the potential for device damage by over-etching in those regions is very high, thus even further negatively impacting the yield.

Contact configuration and method in dual-stress liner semiconductor device

Toshiba America Electronic Components, Inc.