The present invention relates to a novel IL-20 protein which is a member of the cytokine polypeptide family. In particular, isolated nucleic acid molecules are provided encoding the human IL-20 protein. IL-20 polypeptides are also provided as are vectors, host cells and recombinant methods for producing the same. The invention further relates to screening methods for identifying agonists and antagonists of IL-20 activity. Also provided are diagnostic methods for detecting immune system-related disorders and therapeutic methods for treating immune system-related disorders.

The present invention relates to a novel human gene encoding a polypeptide which is a novel human cytokine. More specifically, isolated nucleic acid molecules are provided encoding a human polypeptide named Interleukin 20, hereinafter referred to as xe2x80x9cIL-20xe2x80x9d. IL-20 polypeptides are also provided, as are vectors, host cells and recombinant methods for producing the same. Also provided are diagnostic methods for detecting disorders related to the immune system, and therapeutic methods for treating such disorders.
The invention further relates to screening methods for identifying agonists and antagonists of IL-20 activity.
Cytokines typically exert their respective biochemical and physiological effects by binding to specific receptor molecules. Receptor binding will then stimulate specific signal transduction pathways (Kishimoto, T., et al., Cell 76:253-262 (1994). The specific interactions of cytokines with their receptors are often the primary regulators of a wide variety of cellular processes including activation, proliferation, and differentiation (Arai, K.-I, et al., Ann. Rev. Biochem. 59:783-836 (1990); Paul, W. E. and Seder, R. A., Cell 76:241-251 (1994)).
Human interleukin (IL)-17 was only recently identified. IL-17 is a 155 amino acid polypetide which was molecularly cloned from a CD4+ T-cell cDNA library (Yao, Z., et al., J. Immunol. 155:5483-5486 (1995)). The IL-17 polypeptide contains an N-terminal signal peptide and contains approximately 72% identity at the amino acid level with a T-cell trophic herpesvirus saimiri (HVS) gene designated HVS13. High levels of IL-17 are secreted from CD4-positive primary peripheral blood leukocytes (PBL) upon stimulation (Yao, Z., et al., Immunity 3:811-821 (1995)). Treatment of fibroblasts with IL-17, HVS13, or another murine homologue, designated CTLA8, activate signal transduction pathways and result in the stimulation of the NF-xcexaB transcription factor family, the secretion of IL-6, and the costimulation of T-cell proliferation (Yao, Z., et al., Immunity 3:811-821 (1995)).
An HVS13-Fc fusion protein was used to isolate a murine IL-17 receptor molecule which does not appear to belong to any of the previously described cytokine receptor families (Yao, Z., et al., Immunity 3:811-821 (1995)). The murine IL-17 receptor (mIL-17R) is predicted to encode a type I transmembrane protein of 864 amino acids with an apparent molecular mass of 97.8 kDa. mIL-17R is predicted to possess an N-terminal signal peptide with a cleavage site between alanine-31 and serine-32. The molecule also contains a 291 amino acid extracellular domain, a 21 amino acid transmembrane domain, and a 521 amino acid cytoplasmic tail. A soluble recombinant IL-17R molecule consisting of 323 amino acids of the extracellular domain of IL-17R fused to the Fc portion of human immunoglobulin IgG1 was able to significantly inhibit IL-17-induced IL-6 production by murine NIH-3T3 cells (supra).
Interestingly, the expression of the IL-17 gene is highly restricted. It is typically observed primarily in activated T-lymphocyte memory cells (Broxmeyer, H. J. Exp. Med. 183:2411-2415 (1996); Fossiez, F., et al., J. Exp. Med. 183:2593-2603 (1996)). Conversely, the IL-17 receptor appears to be expressed in a large number of cells and tissues (Rouvier, E., et al., J. Immunol. 150:5445-5456 (1993); Yao, Z., et al., J. Immunol. 155:5483-5486 (1995)). It remains to be seen, however, if IL-17 itself can play an autocrine role in the expression of IL-17. IL-17 has been implicated as a causitive agent in the expression of IL-6, IL-8, G-CSF, Prostaglandin E (PGE2), and intracellular adhesion molecule (ICAM)-1 (Fossiez, F., supra; Yao, Z., et al., Immunity 3:811-821 (1995)). Each of these molecules possesses highly relevent and potentially therapeutically valuable properties. For instance, IL-6 is involved in the regulation of hematopoietic stem and progenitor cell growth and expansion (Ikebuchi, K., et al., Proc. Natl. Acad. Sci. USA 84:9035-9039 (1987); Gentile, P. and Broxmeyer, H. E. Ann. N.Y. Acad. Sci. USA 628:74-83 (1991)). IL-8 exhibits a myelosuppressive activity for stem cells and immature subsets of myeloid progenitors (Broxmeyer, H. E., et al., Ann. Hematol. 71:235-246 (1995); Daly, T. J., et al., J. Biol. Chem. 270:23282-23292 (1995)). G-CSF acts both early and late to activate and stimulate hematopoiesis in general, and more specifically on neutrophil hematopoiesis, while PGE2 enhances erythropoiesis, suppresses lymphopoiesis and myelopoiesis in general, and strongly suppresses monocytopoiesis (Broxmeyer, H. E. Amer. J. Ped. Hematol./Oncol. 14:22-30 (1992); Broxmeyer, H. E. and Williams, D. E. CRC Crit. Rev. Oncol./Hematol. 8:173-226 (1988)).
Thus, there is a need for polypeptides that function as immunoregulatory molecules and, thereby, function in the transfer of an extracelluIlar signal ultimately to the nucleus of the cell, since disturbances of such regulation may be involved in disorders relating to cellular activation, hemostasis, angiogenesis, tumor metastasis, cellular migration and ovulation, as well as neurogenesis. Therefore, there is a need for identification and characterization of such human polypeptides which can play a role in detecting, preventing, ameliorating or correcting such disorders.
The present invention provides isolated nucleic acid molecules comprising a polynucleotide encoding at least a portion of the IL-20 polypeptide having the complete amino acid sequence shown in SEQ ID NO:2 or the complete amino acid sequence encoded by the cDNA clone deposited as plasmid DNA as ATCC Deposit Number 209232 on Aug. 29, 1997. The nucleotide sequence determined by sequencing the deposited IL-20 clone, which is shown in FIG. 1 (SEQ ID NO:1), contains an open reading frame encoding a complete polypeptide of 180 amino acid residues, including an initiation codon encoding an N-terminal methionine at nucleotide positions 45-47, and a predicted molecular weight of about 20.4 kDa. Nucleic acid molecules of the invention include those encoding the complete amino acid sequence excepting the N-terminal methionine shown in SEQ ID NO:2, or the complete amino acid sequence excepting the N-terminal methionine encoded by the cDNA clone in ATCC Deposit Number 209232, which molecules also can encode additional amino acids fused to the N-terminus of the IL-20 amino acid sequence.
The present invention also provides isolated nucleic acid molecules comprising a polynucleotide encoding at least a portion of the IL-20 polypeptide having the complete amino acid sequence shown in SEQ ID NO:15 or the complete amino acid sequence encoded by the cDNA clone deposited in a pool of 50 distinct plasmid DNA molecules as ATCC Deposit Number 209138 on Jul. 3, 1997. The sense and antisense nucleotide sequences determined by 209138 on Jul. 3, 1997. The sense and antisense nucleotide sequences determined by respectively, contain an open reading frame in the sense sequence (SEQ ID NO:28) encoding a polypeptide of 118 amino acid residues, including an initiation codon encoding an N-terminal methionine at nucleotide positions 59-61. Nucleic acid molecules of the invention include those encoding the complete amino acid sequence excepting the N-terminal methionine shown in SEQ ID NO:15, or the complete amino acid sequence excepting the N-terminal methionine encoded by the cDNA clone in ATCC Deposit Number 209138, which molecules also can encode additional amino acids fused to the N-terminus of the IL-20 amino acid sequence. Nucleic acid molecules of the invention further include those encoding any of the N-terminal and/or C-terminal IL-20 deletion mutations with termini of n3 and/or m3 as set forth below.
IL-20 has a predicted leader sequence of 20 amino acids underlined in FIG. 1; and the amino acid sequence of the predicted mature IL-20 protein is also shown in FIG. 1, as amino acid residues 21-180 and as residues 1-160 in SEQ ID NO:2. The encoded polypeptide also has a predicted leader sequence of 20 amino acids of the IL-20 polypeptide of the invention as shown as amino acid residues 1-20 in SEQ ID NO:15, and a predicted mature protein comprising amino acids residues 21-118 of the IL-20 polypeptide of the invention as shown in SEQ ID NO:15.
Thus, one aspect of the invention provides an isolated nucleic acid molecule comprising a polynucleotide having a nucleotide sequence selected from the group consisting of: (a) a nucleotide sequence encoding the IL-20 polypeptide having the complete amino acid sequence in SEQ ID NO:2 (i.e., positions xe2x88x9220 to 160 of SEQ ID NO:2); (b) a nucleotide sequence encoding the IL-20 polypeptide having the complete amino acid sequence in SEQ ID NO:15 (i.e., positions 1 to 118 of SEQ ID NO:2); (c) a nucleotide sequence encoding the IL-20 polypeptide having the complete amino acid sequence in SEQ ID NO:2 excepting the N-terminal methionine (i.e., positions xe2x88x9219 to 160 of SEQ ID NO:2); (d) a nucleotide sequence encoding the IL-20 polypeptide having the complete amino acid sequence in SEQ ID NO:15 excepting the N-terminal methionine (i.e., positions 2 to 118 of SEQ ID NO:15); (e) a nucleotide sequence encoding the predicted mature IL-20 polypeptide having the amino acid sequence at positions 1 to 160 in SEQ ID NO:2; (f) a nucleotide sequence encoding the predicted mature IL-20 polypeptide having the amino acid sequence at positions 21 to 118 in SEQ ID NO:15; (g) a nucleotide sequence encoding the IL-20 polypeptide having the complete amino acid sequence encoded by the cDNA clone contained in ATCC Deposit No. 209232; (h) a nucleotide sequence encoding the IL-20 polypeptide having the complete amino acid sequence encoded by the cDNA clone contained in ATCC Deposit No. 209138; (i) a nucleotide sequence encoding the IL-20 polypeptide having the complete amino acid sequence excepting the N-terminal methionine encoded by the cDNA clone contained in ATCC Deposit No. 209232; (j) a nucleotide sequence encoding the IL-20 polypeptide having the complete amino acid sequence excepting the N-terminal methionine encoded by the cDNA clone contained in ATCC Deposit No. 209138; (k) a nucleotide sequence encoding the mature IL-20 polypeptide having the amino acid sequence encoded by the cDNA clone contained in ATCC Deposit No. 209232; (l) a nucleotide sequence encoding the mature IL-20 polypeptide having the amino acid sequence encoded by the cDNA clone contained in ATCC Deposit No. 209138; and, (m) a nucleotide sequence complementary to any of the nucleotide sequences in (a), (b), (c), (d), (e), (f), (g), (h), (i), (j), (k) or (l), above.
Further embodiments of the invention include isolated nucleic acid molecules that comprise a polynucleotide having a nucleotide sequence at least 90% identical to (that is to say, at most 10% different from), and more preferably at least 95%, 96%, 97%, 98% or 99% identical to (that is to say, at most 5%, 4%, 3%, 2% or 1% different from), any of the nucleotide sequences in (a), (b), (c), (d), (e), (f), (g), (h), (i), (j), (k), (l) or (m), above, or a polynucleotide which hybridizes under stringent hybridization. conditions to a polynucleotide in (a), (b), (c), (d), (e), (f), (g), (h), (i), (j), (k), (l) or (m), above. This polynucleotide which hybridizes does not hybridize under stringent hybridization conditions to a polynucleotide having a nucleotide sequence consisting of only A residues or of only T residues. An additional nucleic acid embodiment of the invention relates to an isolatled nucleic acid molecule comprising a polynucleotide which encodes the amino acid sequence of an epitope-bearing portion of an IL-20 polypeptide having an amino acid sequence in (a), (b), (c), (d), (e), (f), (g), (h), (i), (j), (k) or (l), above. A further nucleic acid embodiment of the invention relates to an isolated nucleic acid molecule comprising a polynucleotide which encodes the amino acid sequence of an IL-20 polypeptide having an amino acid sequence which contains at least one conservative amino acid substitution, but not more than 50 conservative amino acid substitutions, even more preferably, not more than 40 conservative amino acid substitutions, still more preferably not more than 30 conservative amino acid substitutions, and still even more preferably not more than 20 conservative amino acid substitutions. Of course, in order of ever-increasing preference, it is highly preferable for a polynucleotide which encodes the amino acid sequence of an IL-20 polypeptide to have an amino acid sequence which contains not more than 10, 9, 8, 7, 6, 5, 4, 3, 2 or 1 conservative amino acid substitutions.
The present invention also relates to recombinant vectors, which include the isolated nucleic acid molecules of the present invention, and to host cells containing the recombinant vectors, as well as to methods of making such vectors and host cells and for using them for production of IL-20 polypeptides or peptides by recombinant techniques.
The invention further provides an isolated IL-20 polypeptide comprising an amino acid sequence selected from the group consisting of: (a) the amino acid sequence of the full-length IL-20 polypeptide having the complete amino acid sequence shown in SEQ ID NO:2 (i.e., positions xe2x88x9220 to 160 of SEQ ID NO:2); (b) the amino acid sequence of the full-length IL-20 polypeptide having the complete amino acid sequence shown in SEQ ID NO:15 (i.e., positions 1 to 118 of SEQ ID NO:2); (c) the amino acid sequence of the full-length IL-20 polypeptide having the complete amino acid sequence shown in SEQ ID NO:2 excepting the N-terminal methionine (i.e., positions xe2x88x9219 to 160 of SEQ ID NO:2); (d) the amino acid sequence of the full-length IL-20 polypeptide having the complete amino acid sequence shown in SEQ ID NO:15 excepting the N-terminal methionine (i.e., positions 2 to 118 of SEQ ID NO:15); (e) the amino acid sequence of the predicted mature IL-20 polypeptide having the amino acid sequence at positions 1 to 160 in SEQ ID NO:2; (f) the amino acid sequence of the predicted mature IL-20 polypeptide having the amino acid sequence at positions 21 to 118 in SEQ ID NO:15; (f) the complete amino acid sequence encoded by the cDNA clone contained in the ATCC Deposit No. 209232; (g) the complete amino acid sequence encoded by the cDNA clone contained in the ATCC Deposit No. 209138; (h) the complete amino acid sequence excepting the N-terminal methionine encoded by the cDNA clone contained in the ATCC Deposit No. 209232; (i) the complete amino acid sequence excepting the N-terminal methionine encoded by the cDNA clone contained in the ATCC Deposit No. 209138; (j) the complete amino acid sequence of the predicted mature IL-20 polypeptide encoded by the cDNA clone contained in the ATCC Deposit No. 209232; and, (k) the complete amino acid sequence of the predicted mature IL-20 polypeptide encoded by the cDNA clone contained in the ATCC Deposit No. 209138. The polypeptides of the present invention also include polypeptides having an amino acid sequence at least 80% identical to (that is to say, at most 20% different from), more preferably at least 90% identical to (that is to say, at most 10% different from), and still more preferably 95%, 96%, 97%, 98% or 99% identical to (that is to say, at most 5%, 4%, 3%, 2% or 1% different from) those described in (a), (b), (c), (d), (c), (f), (g), (h), (i), (j) or (k), above, as well as polypeptides having an amino acid sequence with at least 90% similarity, and more preferably at least 95% similarity, to those above.
An additional embodiment of this aspect of the invention relates to a peptide or polypeptide which comprises the amino acid sequence of an epitope-bearing portion of an IL-20 polypeptide having an amino acid sequence described in (a), (b), (c), (d), (e), (f), (g), (h), (i), (j) or (k), above. Peptides or polypeptides having the amino acid sequence of an epitope-bearing portion of an IL-20 polypeptide of the invention include portions of such polypeptides with at least six or seven, preferably at least nine, and more preferably at least about 30 amino acids to about 50 amino acids, although epitope-bearing polypeptides of any length up to and including the entire amino acid sequence of a polypeptide of the invention described above also are included in the invention.
A further embodiment of the invention relates to a peptide or polypeptide which comprises the amino acid sequence of an IL-20 polypeptide having an amino acid sequence which contains at least one conservative amino acid substitution, but not more than 50 conservative amino acid substitutions, even more preferably, not more than 40 conservative amino acid substitutions, still more preferably not more than 30 conservative amino acid substitutions, and still even more preferably not more than 20 conservative amino acid substitutions. Of course, in order of ever-increasing preference, it is highly preferable for a peptide or polypeptide to have an amino acid sequence which comprises the amino acid sequence of an IL-20 polypeptide, which contains at least one, but not more than 10, 9, 8, 7, 6, 5,14, 3, 2 or 1 conservative amino acid substitutions.
In another embodiment, the invention provides an isolated antibody that binds specifically to an IL-20 polypeptide having an amino acid sequence described in (a), (b), (c), (d), (e), (f), (g), (h), (i), (j) or (k), above. The invention further provides methods for isolating antibodies that bind specifically to an IL-20 polypeptide having an amino acid sequence as described herein. Such antibodies are useful diagnostically or therapeutically as described below.
The invention also provides for pharmaceutical compositions comprising IL-20 polypeptides, particularly human IL-20 polypeptides, which may be employed, for instance, to treat disorders relating to the proliferation or differentiation of T-cells, cellular activation, hemostasis, angiogenesis, tumor metastasis, cellular migration and ovulation, as well as neurogenesis. Methods of treating individuals in need of IL-20 polypeptides are also provided.
The invention further provides compositions comprising an IL-20 polynucleotide or an IL-20 polypeptide for administration to cells in vitro, to cells ex vivo and to cells in vivo, or to a multicellular organism. In certain particularly preferred embodiments of this aspect of the invention, the compositions comprise an IL-20 polynucleotide for expression of an IL-20 polypeptide in a host organism for treatment of disease. Particularly preferred in this regard is expression in a human patient for treatment of a dysfunction associated with aberrant endogenous activity of IL-20.
The present invention also provides a screening method for identifying compounds capable of enhancing or inhibiting a biological activity of the IL-20 polypeptide, which involves contacting a receptor which is enhanced by the IL-20 polypeptide with the candidate compound in the presence of an IL-20 polypeptide, assaying the IL-6 secretion or lymphocyte proliferation activity of the receptor in the presence of the candidate compound and of IL-20 polypeptide, and comparing the receptor activity to a standard level of activity, the standard being assayed when contact is made between the receptor and in the presence of the IL-20 polypeptide and the absence of the candidate compound In this assay, an increase in receptor activity over the standard indicates that the candidate compound is an agonist of IL-20 activity and a decrease in receptor activity compared to the standard indicates that the compound is an antagonist of IL-20 activity.
In another aspect, a screening assay for)agonists and antagonists is provided which involves determining the effect a candidate compound has on IL-20 binding to a receptor. In particular, the method involves contacting the receptor with an IL-20 polypeptide and a candidate compound and determining whether IL-20 polypeptide binding to the receptor is increased or decreased due to the presence of the candidate compound. In this assay, an increase in binding of IL-20 over the standard binding indicates that the candidate compound is an agonist of IL-20 binding activity and a decrease in IL-20 binding compared to the standard indicates that the compound is an antagonist of IL-20 binding activity.
In yet another aspect, the IL-20 polypeptide may bind to a cell surface protein which also function as a viral receptor or coreceptor. Thus, IL-20, or agonists or antagonists thereof, may be used to regulate viral infectivity at the level of viral binding or interaction with the IL-20 receptor or coreceptor or during the process of viral internalization or entry into the cell.
It has been discovered that IL-20 is expressed not only in thymus, but also in thymus tumor and 12 week old whole human embryo. Therefore, nucleic acids of the invention are useful as hybridization probes for differential identification of the tissue(s) or cell type(s) present in a biological sample. Similarly, polypeptides and antibodies directed to those polypeptides are useful to provide immunological probes for differential identification of the tissue(s) or cell type(s). In addition, for a number of disorders of the above tissues or cells, particularly of the immune, significantly higher or lower levels of IL-20 gene expression may be detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) taken from an individual having such a disorder, relative to a xe2x80x9cstandardxe2x80x9d IL-20 gene expression level, i.e., the IL-20 expression level in healthy tissue from an individual not having the immune system disorder. Thus, the invention provides a diagnostic method useful during diagnosis of such a disorder, which involves: (a) assaying IL-20 gene expression level in cells or body fluid of an individual; (b) comparing the IL-20 gene expression level with a standard IL-20 gene expression level, whereby an increase or decrease in the assayed IL-20 gene expression level compared to the standard expression level is indicative of disorder in the immune system.
A further consequence of the observed thymus-restricted expression of endogenous IL-20 is that the IL-20 of the present invention may be useful in the regulation of the proliferation or differentiation of T-cells in general, for specific subsets of T-cells, for other immune cells in general, for other specific subsets of other immune cells, or any combination thereof. Thus, IL-20 of the present invention may be used therapeutically to treat disorders related to the immune system, including autoimmune and hematopoietic diseases or disorders, including AIDS, arthritis, or normal or abnormal cellular or systemic processes related to aging, and the like.
An additional aspect of the invention is related to a method for treating an individual in need of an increased level of IL-20 activity in the body comprising administering to such an individual a composition comprising a therapeutically effective amount of an isolated IL-20 polypeptide of the invention or an agonist thereof.
A still further aspect of the invention is related to a method for treating an individual in need of a decreased level of IL-20 activity in the body comprising, administering to such an individual a composition comprising a therapeutically effective amount of an IL-20 antagonist. Preferred antagonists for use in the present invention are IL-20-specific antibodies.


A method of manufacturing a vibration damping bushing wherein after setting a main shaft member on a lower mold, an medial sleeve is set to be disposed about the main shaft member, and a plurality of sections are moved forward in a centripetal direction to form an intermediate mold together, and then an upper mold is superposed onto the intermediate mold to form a mold cavity therein. At least one positioning protrusion is formed on a cavity defining face, being discontinuous in a circumferential direction, while being located at either semi-circumference of the cavity defining face with any diametric line interposed therebetween. The medial sleeve is set in position in an axis-perpendicular direction within the mold cavity by holding the positioning protrusions in contact against an outer peripheral face of the medial sleeve. A vibration damping bushing manufactured by this method is also disclosed.

1. Field of the Invention
The present invention relates to a vibration damping bushing adapted to provide vibration damping linkage to two components for which vibration transmission is to be prevented in an automobile, or alternatively adapted to provide vibration damping mounting of one of the two components on the other in a vibration damping fashion. The present invention also relates to a method of producing the same.
2. Description of the Related Art
Conventionally, suspensions for automobiles and the like have commonly employed vibration damping bushings composed of a main shaft member, a rubber elastic body of tubular shape affixed to the outside peripheral face of the main shaft member, and a medial sleeve of tubular shape embedded coaxially in the medial region of the rubber elastic body in the direction of its thickness. This vibration damping bushing is of press fit design, intended to be used by press-fitting the rubber elastic body directly into a mounting hole, or press-fitting the rubber elastic body into an outer tube member, then press-fitting the outer tube member into a mounting hole.
As disclosed in JP-A-9-72365 and JP-A-11-141612 for example, vibration damping bushings of this kind are manufactured typically through vulcanization molding of a rubber material together with the main shaft member and the medial sleeve which have been positioned in the mold, thereby integrally molding the rubber elastic body with these components. The mold assembly used for this process is composed, for example, of an upper mold and a lower mold positioned spaced some distance apart in the vertical direction, and intermediate molds split into several sections in the circumferential direction and positioned extendably and retractably in the centripetal direction between the upper and lower molds.
Where a vibration damping bushing is manufactured using this type of mold assembly, first, the main shaft member and the medial sleeve are disposed resting upright (i.e. oriented with the axial direction aligned with the vertical) and disposed concentrically, with a first end thereof (the lower end) positioned on a positioning member disposed on the upper face of the lower mold of the mold assembly. Next, the lower mold is transported to a prescribed location, the intermediate molds are moved in the centripetal direction and set with respect to the lower mold, then again transported to a prescribed location where the upper mold is set and the mold assembly is locked. The mold assembly is then moved to the location of the vulcanizer where the vulcanizer injects rubber material into the mold cavity and carries out vulcanization molding. Then, prescribed post-processing steps are carried out to complete the vibration damping bushing.
Where a vibration damping bushing is manufactured in the above manner, the main shaft member and the medial sleeve are positioned concentrically by a positioning member disposed on the upper face of the lower mold of the mold assembly. At this time, while the main shaft member can be held in stable condition by the positioning member, for structural reasons portion of the medial sleeve held by the positioning member (i.e. the portion projecting from the axial end face of the rubber elastic body) is insufficient. Moreover, since there is dimensional variation (tolerance) of the medial sleeve, it is necessary to leave a gap (gutter) in the diametrical direction between the medial sleeve and the positioning member, so that the sleeve tends to be held in an unstable condition.
Thus, when the lower mold is transported to the prescribed location for the next process, the medial sleeve can easily shift out of position, for example, assuming a tilted state, or running up onto the positioning member. If the medial sleeve should shift out of position in this way, when the intermediate molds and the upper mold are set, the mold assembly or medial sleeve may become broken or deformed. Also, if vulcanization molding is carried out with the medial sleeve shifted out of position, dimensional accuracy of the product will be poor so that characteristics vary appreciably, or defective products may occur.
In order to prevent the medial sleeve from shifting out of position in this way, it may be contemplated to extend the length of the medial sleeve projecting beyond the axial end face of the rubber elastic body. However, since it is necessary to avoid interference with other components situated in proximity to the vibration damping bushing, there is a limit as to how much the length of the medial sleeve can be extended.

Method of manufacturing a vibration damping bushing


The present invention aims to provide a novel cyclin-dependent kinase 8 and/or 19 inhibitor useful as an anti-cancer agent. The present invention relates to a cyclin-dependent kinase 8 and/or 19 inhibitor containing a compound represented by the formula (I):

CDK is a phosphoenzyme that is activated by forming a complex with a cyclin protein, and is known as a factor involved in cell cycle and transcriptional regulation. In particular, it is known that CDK2, CDK4 and CDK6 are mainly involved in the cell cycle, and CDK7, CDK8 and CDK9 are mainly involved in transcription. Among them, CDK8 forms a complex with cyclin C, MED12 and MED13, and acts as a kinase that mainly controls transcription by controlling phosphorylation of the C-terminal domain and the like of RNA polymerase II (non-patent document 1).
It has been reported that CDK8 is an oncogene in a part of colorectal cancer cells, and CDK8 expression is promoted in colorectal cancer patients, which activates F3-catenin signal and positively controls cell proliferation (non-patent document 2). Furthermore, CDK8 is known to be also involved in the maintenance of undifferentiated state of cancer cells and epithelial mesenchymal transition.
In addition, it has been reported that CDK8 inhibitor Cortistatin A suppresses proliferation of various cancer cells and particularly shows remarkable effects on leukemia cells (non-patent document 3).
Non-patent document 4 discloses that a compound that inhibits CDK8 is useful for the treatment or prophylaxis of cancer, and patent documents 1-6 disclose CDK inhibitors having an anti-cancer action.
Patent document 7 discloses a novel aromatic compound having an osteogenesis promoting action. However, the action of these compounds on CDK8 and/or CDK19 is not known.

Cyclin-dependent kinase 8 and/or 19 inhibitor

Abstract: [wherein each symbol is as defined in the DESCRIPTION] or a pharmaceutically acceptable salt thereof as an active ingredient, and use thereof as an agent for preventing and/or treating cancer.


The disclosed article comprises a semiconductor laser (typically a multi-segment DBR laser) and feedback means for controlling the laser wavelength. The wavelength reference element in the feedback means advantageously is an optical fiber comprising an in-line refractive index grating. Such gratings frequently have a transmission spectrum that exhibits subsidiary lobes, in addition to the desired main lobe, potentially compromising the "cold-start" ability of prior art systems. This and other drawbacks of prior art systems exemplarily are overcome by apparatus that comprises a feedback loop that comprises means for causing a current I.sub.B to flow to the "Bragg" section of a multi-segment DBR laser such that wavelength of the laser output is a function of I.sub.B, and that further comprises means for changing the temperature of the laser in response to a change in the wavelength of the laser. Use of a wavelength reference element that has a relatively wide primary minimum facilitates cold starting. Exemplarily, the disclosed article is a wavelength division multiplexed (WDM) optical fiber communication system.

Wavelength division multiplexed (WDM) optical fiber communication systems are known. Such a system typically comprises wavelength reference means and feedback means that maintain the wavelength of the output radiation of a laser at a predetermined value.
Exemplarily, reference means comprise optical fiber with in-line refractive index grating. See, for instance, U.S. Pat. No. 5,077,816, which discloses a wavelength multiplexed fiber communication system that comprises a narrow band (e.g., 60 GHz tuning range) semiconductor laser and a narrow band (e.g., 44 GHz) refractive index reflection grating, with the feedback loop locking the laser output to the center frequency of the grating. See also C. R. Giles et al., IEEE Photonics Technology Letters, Vol. 2(1), p. 63, which discloses use of an Er-YAG optical filter, and use of a feedback loop to control the current to the Bragg section of a two-section DBR laser.
Some shortcomings are associated with prior art wavelength stabilization schemes. The scheme of the '816 patent involves use of a narrow band laser. However, it would frequently be desirable to be able to use lasers having a broad tuning range such that nominally identical (broad band) lasers could be used as sources in a WDM system, thus avoiding the need to use specially designed lasers for the various channels. The Giles et al. scheme typically does not provide access to all wavelengths within the tuning range of a (broad-band) laser. Such access typically would be desirable. The scheme of the '816 patent typically is not capable of start-up without human intervention ("cold-start") if the wavelength reference means (typically an in-line refractive index grating) does not have a single transmission minimum but exhibits also one or more subsidiary minima, as is frequently the case. It would clearly be desirable to have available a stabilization scheme that is capable of cold-start even under those circumstances. Finally, it would be desirable to have available a stabilization scheme that facilitates some choice in the control frequency, such that (typically unavoidable) small deviations from the target wavelength of the wavelength reference means can be readily compensated for. This application discloses an article that comprises a laser stabilization scheme that mitigates or eliminates at least some of the above recited shortcomings of the prior art schemes.

Article comprising a wavelength-stabilized semiconductor laser


A new cultivar of Euphorbia named ‘NOTHOWLEE’ that is distinguished by a compact clumping growth habit, dark purple foliage, and terminal cymes that open into bronze floral heads that completely cover the plant from May through summer. In combination, these characteristics provide a long period of garden interest and set ‘NOTHOWLEE’ apart from all other existing varieties of Euphorbia known to the inventor.

The present invention relates to a new and distinct cultivar of Euphorbia, a hardy perennial that is grown for use as an ornamental landscape plant. The new invention will be referred to hereinafter by the cultivar name 'NOTHOWLEE'.
'NOTHOWLEE' was discovered by the inventors in April 2002 in Woodbridge, Suffolk, England. The inventors first observed 'NOTHOWLEE' as a naturally occurring single whole plant which was found by the inventors to be growing within a commercial crop of the variety of Euphorbia named 'Charam' U.S. Plant patent application Pending, Ser. No. 09/944,932, filed Aug. 31, 2001). The inventors observed that the foliage of 'NOTHOWLEE' was strikingly different from the foliage of the surrounding plants of 'Charam'. The foliage of 'NOTHOWLEE' is predominantly dark purple in coloration whereas the foliage of 'Charam' is the typical mid green for the species and hybrids of Euphorbia martinii and Euphorbia characias.
The inventors removed 'NOTHOWLEE' from the crop of 'Charam' and continued to observe 'NOTHOWLEE' as it came into flower. The flowers which take the form of terminal cymes appear first as a bronze canopy which complements the dark purple foliage.
The closest comparison plant to 'NOTHOWLEE' known to the inventors is the parent variety, 'Charam'. Whereas 'NOTHOWLEE' has similar growth habit to 'Charam', the colors of the foliage of 'NOTHOWLEE' and 'Charam' are dark purple and mid green respectively; and the colors of the inflorescence of 'NOTHOWLEE' and 'Charam' are bronze and yellow respectively.
The first asexual reproduction of 'NOTHOWLEE' was accomplished by the inventors using the method of tip cuttings and was carried out in June 2002 in Woodbridge, Suffolk England. The inventors determined that the plants that grew from this first asexual reproduction appeared to be identical to the original single plant of 'NOTHOWLEE'. Subsequent generations which have been propagated similarly have confirmed to the inventors that 'NOTHOWLEE' is a stable variety which reproduces true to type.
The inventors have filed an application for a grant of European Community Plant Breeders Rights, serial number 2004/0626, filed Mar. 30, 2004.
The first public sale or distribution of plants of 'NOTHOWLEE' took place on Apr. 6, 2005 in Woodbridge, Suffolk, England.


The present disclosure describes novel peptidomimetic compounds which contain a novel class of isosteres and which inhibit the proteolytic activity of HIV protease and further describes therapeutic compositions comprising said compounds, a method of treatment for patients having the AIDS virus involving administering a therapeutically effective amount of the novel compounds of the present invention, and a method of preparation for said isosteres.

Enzyme activity is known to be a vital factor in the lifecycle of viruses which infect mammals. Effective inhibitors of viral enzymes would, therefore, be useful therapeutic tools in the treatment of viral infections such as by HIV (Human Immunodeficiency Virus), and viral infection related diseases such as AIDS (Acquired Immune Deficiency Syndrome)aand ARC (AIDS Related Complex).
HIV, the causative agent of the AIDS, is a member of the lentivirus family of retroviruses (Gonda et al., 1985, "Sequence Homology and Morphological Similarity of HTLV III and Visna Virus, A Pathogenic Lentivirus", Science, 227:173; Sonigo et al., 1985, "Nucleotide Sequence of the Visna Lentivirus: Relationship to the AIDS Virus", Cell, 42:369). HIV, in common with other retroviruses, encodes a number of enzymes that are necessary for its life cycle (Weiss et al., 1982, The Molecular Biology of RNA Tumor Viruses, 2nd ed., Cold Spring Harbor Laboratory, New York; Ratner et al., 1985, "Complete Nucleotide Sequence of the AIDS Virus, HTLV III", Nature, 313:277). In the absence of such enzymes, viable viral infections do not occur (Weiss et al., supra).
The only currently used therapeutic for AIDS, AZT, is an inhibitor of the viral reverse transcriptase (Mitsuya et al., 1986, "Inhibition of the In Vitro Infectivity and Cytopathic Effects of HTLV III", Proc. Natl. Acad. Sci. U.S.A. 83:1911). Other known viral enzymes include an RNAse, an integrase and a protease, all of which are essential for the viral life cycle (Mitsuya et al., 1987, "Strategies for Antiviral Therapy in AIDS", Nature, 325:773).
The protease found in HIV (hereinafter "HIV protease") is responsible for cleavage of the gag and gag-pol polyproteins into mature peptides (Ratner et al. supra; Kramer et al., 1986, "HTLV III Gag Protein is Processed in Yeast cells by the Virus Pol Protease", Science, 231:1580; Farmerie et al., 1987, "Expression and Processing of the AIDS Virus Reverse Transcriptase in Escherichia coli", Science, 236:305). The amino acid sequence for the gag polyprotein is described in Ratner et al, 1985, Nature, 313:277.
From the known location at the 5' end of the pol gene and the inferred protease cleavage sites (Pearl et al., 1987, "Sequence Specificity of Retroviral Proteases," Nature, 328:482), the predicted size of the protease is 99 amino acids. HIV protease, as with other retroviral proteases, has a homology with cellular aspartyl proteases (Katch et al., 1987, "Inhibition of Retroviral Protease Activity by an Aspartyl Proteinase Inhibitor", Nature, 329:654 ).
Kohl et al., 1988, "Active Human Immuno-deficiency Virus Protease is Required for Viral Infectivity.", Proc. Natl. Acad. Sci. U.S.A., 85:4686, demonstrated that active HIV protease participation is required for HIV replication. The article by J. R. Huff, 1991, "HIV Protease: A Novel Chemotherapeutic Target for AIDS.", J. Med. Chem., 34:2305, is a state of the art review of currently documented HIV protease inhibitors.
The inventive compounds differ from those taught in the prior art of which the applicants are aware in that they represent peptidomimetics which contain a novel class of isosteres which are not presently known.

Proline derivatives and compositions for their use as inhibitors of HIV protease


Techniques for processing a query are provided. One or more operations that are required to process a query are performed by a coprocessor that is separate from a general purpose microprocessor that executes query processing software. The query processing software receives a query, determines one or more operations that are required to be executed to fully process the query, and issues one or more commands to one or more coprocessors that are programmed to perform one of the operations, such as a table scan operation and/or a lookup operation. The query processing software obtains results from the coprocessor(s) and performs one or more additional operations thereon to generate a final result of the query.

The approaches described in this section are approaches that could be pursued, but not necessarily approaches that have been previously conceived or pursued. Therefore, unless otherwise indicated, it should not be assumed that any of the approaches described in this section qualify as prior art merely by virtue of their inclusion in this section.
Queries issued to a database typically target one or more one or more database objects, such as relational tables. Many times, accessing data organized in a relational table involves scanning the relational table or at least a portion thereof. A common SQL query is one that requires a filter on a database table, such as the following:                select EMPLOYEE from T_EMPLOYEES where HIRE_YEAR='2012'
In this example, that database table T_EMPLOYEES is searched for all the employees who were hired in 2012. This search (or "scan") is done by software running on one or more microprocessors that execute a series of instructions to search through the table for the specified value, which is '2012' in this example. The first step is typically the performance bottleneck when running analysis applications on a large database, since this step has to run on the entire table, which may be several terabytes large. Subsequent steps will work on the filtered subset of the first scan step that meets the criteria set in the scan (employees hired in 2012 in the above example). Therefore, the number of rows that a machine can filter per unit of time is an important performance metric for the machine. This metric is referred to as the "scan rate."
Approaches for processing queries, such as queries that involve scanning a table, have relied on software techniques, where the software is executed (or "runs") on a general purpose microprocessor.

This patent is subject to a terminal disclaimer.

Hardware for performing a database operation


A current control circuit which controls currents flowing in memory cells in a non-volatile semiconductor memory device includes a circuit which controls the currents flowing in the memory cells in an erase operation so that amounts of the currents fall within a tolerable range.

1. Field of the Invention
The present invention generally relates to non-volatile semiconductor memory devices of an electrically erasable type. More particularly, the present invention is concerned with a non-volatile semiconductor memory device of a batch erase type such as a flash memory device in which data stored in a plurality of memory cells can be electrically erased at one time. More specifically, the present invention relates to improvements in a circuit configuration directed to erasing data stored in memory cells at one time.
The flash memory is an electrically programmable and erasable device and can be relatively easily implemented by using the integrated circuit technology. Further, the flash memory is of non-volatile type. From these viewpoints, the flash memory is attractive and is used in various applications such as an external storage device and a portable telephone set.
2. Description of the Related Art
FIG. 1A is a cross-sectional view of a cell of a flash memory device, and FIG. 1B shows an operation thereof. Referring to FIG. 1A, a P-type semiconductor substrate 1 has N.sup.+ -type impurity diffused regions 2 and 3, which function as a drain and a source of the cell transistor, respectively. A channel can be formed between the drain 2 and the source 3. An insulating film (not shown) is formed on the channel. A floating gate FG is formed on the insulating film. An insulating film is formed on the floating gate FG, and a control gate CG is formed on the insulating film. In FIGS. 1A and 1B, symbols Vd, Vs and Vg respectively denote a drain voltage, a source voltage and a gate voltage.
Data can be written into the memory cell as follows. The drain voltage Vd is set to a first voltage Vp. The voltages Vd and Vp are equal to or lower than, for example, 6V (Vd=Vp=.about.6V). The gate voltage Vg is set to a second voltage Vpp, which is higher than the voltage Vp (>Vp). Further, the source voltage Vs is set to 0V, which is the reference potential with respect to the voltages. Hence, as indicated by *1 in FIG. 1A, electrons are injected in the floating gate FG from the drain.
Data can be erased as follows. The source voltage Vs is set to a third voltage Vcc, which is lower than the first voltage Vp and is equal to or lower than, for example, 5V. The gate voltage Vg is set to a negative voltage which is lower than 0V, and the drain is set to an open state. Hence, as indicated by *2, the electrons are drawn to the source from the floating gate FG.
Data can be read as follows. The gate voltage Vg is set to the third voltage Vcc, and the drain voltage Vd is set to a voltage equal to or lower than 1V (Vd=.about.1V). In this case, it is determined whether a current flows in the drain. In other words, it is determined whether the data stored in the cell is "1" or "0". The second voltage Vpp is called a write/erase voltage, and the third voltage Vcc is a read voltage.
Generally, the erase operation of the flash memory is not carried out on the cell basis but a group of cells (for example, every 64 Kbytes) are erased at one time. Such a group is called "sector". Current control circuits are provided to respective sectors. Data is erased by causing the source current to flow in the cell. In this point of view, the current control circuits are also called source current control circuits.
FIG. 2 is a block diagram of a configuration of the flash memory which employs the sector-basis erasing operation. The flash memory shown in FIG. 2 includes a plurality of sectors 10.sub.1 through 10.sub.n where n is an integer. The sectors 10.sub.1 through 10.sub.n respectively include cell arrays 14.sub.1 through 14.sub.n and source current control circuits 12.sub.1 through 12.sub.n. The source current control circuits 12.sub.1 through 12.sub.n are connected, via a wiring line 16, to a current source to which a power supply generating the third (power supply) voltage Vcc is connected. Symbols R1 through Rn denote wiring resistances of portions between the adjacent sectors.
FIG. 3 is a circuit diagram of the source current control circuit 12.sub.1. Each of the other source current control circuits 12.sub.2 through 12.sub.n has the same configuration as shown in FIG. 3. The source current control circuit 12.sub.1 includes P-channel field effect transistors (for example, MOS transistors) MP1 and MP2, and N-channel field effect transistors (for example, MOS transistors) MN1 and MN2. An erase signal ER1 for the sector 10.sub.1 is applied to the gates of the transistors MP1 and MN1, which are set to a high level during the erasing operation. The current source shown in FIG. 2 is connected to the source of the transistor MP2. The drains of the transistors MP2 and MN2 are connected together and are further connected to the cell array 14.sub.1.
When data stored in the cell array 14.sub.1 are erased at one time in the batch formation, the erase signal ER for the sector 10.sub.1 is set to the high level. Hence, the transistor MN1 is turned ON, and the transistor MP2 is turned ON. Hence, as indicated by the thick solid line, a current I1 is supplied to the cell array 14.sub.1 from the current source via the transistor MP2.
However, the above prior art has the following disadvantages.
As has been described previously, the wiring line 16 have the wiring resistances R1 through Rn. Since the source current control circuits 12.sub.1 through 12.sub.n have the same circuit configuration, the source currents I1 through In flowing in the cell arrays 14.sub.1 through 14.sub.n have different values which depend on the wiring resistances R1 through Rn. That is, the selector 10.sub.1 is connected to the current source via the resistance R1, so that the largest source current I1 flows in the cell array 14.sub.1. In contrary, the selector 10.sub.n is connected to the current source via the resistances R1 through Rn, so that the smallest source current In flows in the cell array 14.sub.n. That is, as shown in FIG. 4, the source currents I1, I2, I3, . . . , In have decreased values in that order. FIG. 4 shows Vs-Is (source voltage vs source current) characteristics of the source current control circuits 12.sub.1, 12.sub.2 and 12.sub.3, in which the horizontal axis denotes the source voltage Vs and the vertical axis denotes the source current Is.
Since the source currents Is of the sectors 10.sub.1 through 10.sub.n have different values, different magnitudes of stress are applied to the memory cells of the memory cell arrays 14.sub.1 through 14.sub.n. The above fact causes the following problems. For example, even if the source current I1 has an amount which certainly ensures the erasing operation on the cell array 14.sub.1, the source current In may be insufficient to certainly ensure the erasing operation on the cell array 14.sub.n during the same erasing time as that for the cell array 14.sub.1. If the source current In has an amount which certainly ensures the erasing operation on the cell array 14.sub.n, the source current I1 may excessively erase data stored in the cells of the cell array 14.sub.1 during the same erasing time as that for the cell array 14.sub.n. If the cells are excessively subjected to the erasing operation, the electrons stored in the floating gate FG are reduced. It can be seen from the above that it is necessary to change the erasing time in accordance with the amount of the source current in order to eliminate the above problems.
However, if a plurality of sectors are simultaneously subjected to the erasing operation, the above problems cannot be eliminated. For example, a plurality of sectors are subjected to the simultaneous erasing operation in a test carried out before shipping in order to reduce the test time. Even if the source currents are supplied to the sectors during the same time, the source currents supplied to the different sectors have different amounts, so that the sectors have different erased states.
If a common erasing time is defined as the erasing time necessary to obtain a desired erased state by the source current which has the smallest amount among the source currents supplied to the sectors subjected to the simultaneous erasing operation, some sectors supplied with comparatively large amounts of source currents will be excessively erased. In contact, if the common erasing time is defined as the erasing time necessary to obtain the desired erased state by the source current which has the smallest amount among the source currents supplied to the sectors subjected to the simultaneous erasing operation, some sectors supplied with comparatively small amounts of source currents will be insufficiently erased. Hence, the reliability of the flash memory will be degraded.

Current control circuit and non-volatile semiconductor memory device having the same


A patient support structure for supporting a patient in a supine position for surgery and a method for use of the patient support structure is provided. The patient support structure includes a back support portion, a neck support portion, and a head support portion. The back support portion includes a panel portion and padding padding movably attached to relative to the upper surface. The neck support portion includes an adjustable neck support pad and at least a first rotational adjustment assembly, where the first rotational adjustment assembly is configured to eccentrically rotate the neck support pad about an axis offset from a central axis of the rotatable neck pad. The head support portion includes at least one base portion, a first arm portion, a second arm portion, and a head harness, where the first arm portion and the second arm portion are adjustable inwardly/outwardly and upwardly/downwardly, and the head harness is supported by the first arm portion and the second arm portion.

Operating room tables are used to support a patient thereon during surgery. Typically, conventional operating room tables oftentimes have some form of coarse adjustment for generally adjusting portions of a patient's body. To illustrate, conventional operating room tables often have a first end portion, a second end portion, and a body portion positioned between the first end portion and the second end portion, where the first end portion and the second end portion are each pivotable with respect to the body portion. When a patient is positioned on such conventional operating room tables, the patient's buttocks and lower back, the first end portion can be pivoted to adjust the position of the upper portion of the patient's body, and the second end portion can be pivoted to adjust the position of the lower portion of the patient's body. However, such coarse adjustment of the patient's body does not provide fine adjustment of the patient's torso, neck, and head that may be necessary for some surgeries. Oftentimes, separate padding is inserted between the patient's body parts and the surfaces of such conventional operating room tables to position the patient's torso, neck, and head for surgery. However, such separate padding is oftentimes unwieldly and can be a challenge to adjust for surgery. Therefore, there is a need for a device that can be attachable to or integrated into an operating room table for adjustably supporting portions of a patient's buttocks, back, neck, and head thereon to finely position these body parts before, during, and after surgery.

Device for adjustably supporting portions of a patient for surgery


A non-volatile memory (NVM) cell includes a semiconductor wire including a select gate portion and a control gate portion. The NVM cell includes a select transistor formed with the select gate portion and a control transistor formed with the control gate portion. The select transistor includes a gate dielectric layer disposed around the select gate portion and a select gate electrode disposed on the gate dielectric layer. The control transistor includes a stacked dielectric layer disposed around the control gate portion, a gate dielectric layer disposed on the stacked dielectric layer and a control gate electrode disposed on the gate dielectric layer. The stacked dielectric layer includes a first silicon oxide layer disposed on the control gate portion, a charge trapping layer disposed on the first silicon oxide, and a second silicon oxide layer disposed on the charge trapping layer.

As the semiconductor industry has progressed into nanometer technology process nodes in pursuit of higher device density, higher performance, and lower costs, challenges from both fabrication and design issues have resulted in the development of three-dimensional designs. Integration of a non-volatile memory in a semiconductor device has been required to achieve a higher functionality of the semiconductor device.

Method of manufacturing a semiconductor device and a semiconductor device

TAIWAN SEMICONDUCTOR MANUFACTURING CO., LTD.


In accordance with an embodiment, a receiver includes a first state machine configured to be coupled to a bus. The first state machine is configured to determine that a first output signal is a first symbol if a first received bus signal transitions from a first bus state to a second bus state and stays in the second bus state for less than a first predetermined period of time, and the first output signal is a second symbol if the first received bus signal transitions from the first bus state to the second bus state and stays in the second bus state for at least the first predetermined period of time.

Communications networks that interconnect electronic components in a vehicle may operate under one or more protocols such as the Controller Area Network (CAN), Local Interconnect Network (LIN), and the FlexRay protocol. In automotive systems, in particular the operation of these automotive networks is often subject to safety and reliability requirements to ensure the safety of the automobile and its passengers. For example, robustness against absorbed radiation and suppressing of the generation of radiation may be a part of a conformance test.
The FlexRay protocol utilizes a high data rate up to 10 Mbit/s to connect automotive electronic control units (ECUs), such as electronic control modules (ECM), transmission control modules (TCM), brake control modules (BCM)), Central Control Modules (CCM), Central Timing Modules (CTM), General Electronic Modules (GEM), Body Control Modules (BCM), Suspension Control Modules (SCM), control units, or control modules. Dual wires are used as the medium for communications, and signaling on the bus is accomplished by asserting a differential voltage between those two wires in the FlexRay protocol. The bus may have three states: two data states and an idle state. Also, the FlexRay protocol limits the propagation delay, jitter, EMC requirements, network topologies, and functional transceiver operation modes for the communications network. For example, the network topology may include point-to-point connections via linear passive busses and passive stars up to active star topologies. One component of a communications network is a receiver, which is used to receive and transform a signal, for example a bus signal. For example, a receiver converts the information carried by the signal to a usable form, for example by converting an analog signal to a digital signal.


An Al-based intermetallic compound in which a eutectic crystal type Al-CuMn intermetallic compound dispersion phase is dispersed in an Al-Cu intermetallic compound matrix phase. The content of Mn as a eutectic crystal-forming element contained in the dispersion phase is set in a range of from 5% by weight (inclusive) to 30% by weight (inclusive). In the course of solidification of the Al-Cu-Mn intermetallic compound, an infinite number of dispersion phases are first crystallized, and the matrix phase is then crystallized. This ensures that the matrix phase is formed into a fine crystal structure due to hindrance of the growth thereof by the dispersion phase, leading to increases in hardness and toughness of the resulting Al-based intermetallic compound. In another embodiment, the Al-based intermetallic compound contains peritectic type Al-based intermetallic dispersion phase, such as formed by Ta, dispersed in the intermetallic compound matrix phase.

1. Field of the Invention
The field of the present invention is aluminum-based (Al-based) intermetallic compounds with a high toughness and a high wear resistance.
2. Description of the Prior Art
There are conventionally known Al-based intermetallic compounds containing Ni as an intermetallic compound forming element (for example, see Japanese Patent application Laid-open No. 166982/86).
However, the prior art Al-based intermetallic compounds are accompanied by a problem that the entire compound comprises an aluminum/nickel-based compound phase and hence, it has a high hardness and thus a high wear resistance, but is brittle and has a low toughness.

Aluminum-based intermetallic compound with high toughness and high wear resistance


An intercepting user equipment and a lawful interception method thereof are provided. The intercepting user equipment registers to the administrating server for lawful interception, and then receives a positive interception message from the administrating server. The intercepting user equipment receives a signal from user equipment, and determines whether a power measurement of the signal exceeds a threshold. If positive, the intercepting user equipment transmits a power adjustment request to the administrating server so that the administrating server notifies the eNB of transmitting a power adjustment command to the user equipment for adjusting transmitting power. The intercepting user equipment intercepts communication data of the user equipment.

For security reasons, legal communication intercepting techniques are necessary. In the general communication systems, mobile stations connect to backend network directly, and have to exchange data (voice data, text data etc.) with each other via the backend network. In other words, the data exchanged between the mobile stations must be processed by the backend work. Therefore, when an inception is authorized by the court, an authorized user needs to ask the operator of the backend network for obtaining the data which is exchanged between the mobile stations and stored in the backend network.
However, in the developing 3GPP direct mode communication network, although mobile stations still connect to backend network, they exchange data with each other directly. In other words, in 3GPP direct mode communication network, the data exchange between the mobile stations will not be processed by the backend network. Accordingly, an authorized user cannot obtain the data exchanged between the mobile stations from the backend network since the data may not be stored in the backend network.
Accordingly, in order to implement lawful interception for 3GPP direct mode communication network, corresponding protocols and hardware devices differed from the general communication system are needed.

Intercepting user equipment and lawful interception method thereof for use in 3GPP direct mode communication


A surgical articulation assembly is disclosed, including a control assembly and an articulable portion. The articulable portion includes at least two segments capable of independent movement. The control assembly defines an axis and three user controls configured to be engaged by an operator. Disposed within the control assembly are three pairs of diametrically opposed driving members that effects translation of a connecting member upon engagement of the user controls. An end of the connecting member is attached to one of the first and second segments of the articulable portion. As the connecting member translates with the driving members, the three user controls allow an operator to exert forces at points along the articulable portion. Also disclosed is a method of effecting articulation of a surgical articulation assembly.

1. Technical Field
The present disclosure relates generally to a surgical device for use in a minimally invasive surgical procedure. More particularly, the present disclosure relates to an articulating surgical assembly having at least a first segment and a second segment that are separately movable.
2. Background of Related Art
A minimally invasive surgical procedure is one in which a surgeon enters a patient's body through one or more small opening in the patient's skin or a naturally occurring opening (e.g., mouth, anus, or vagina). As compared with traditional open surgeries, minimally invasive surgical procedures have several advantages and disadvantages. Minimally invasive surgeries include arthroscopic, endoscopic, laparoscopic, and thoracic surgeries. Advantages of minimally invasive surgical procedures over traditional open surgeries include reduced trauma and recovery time for patients.
However, some disadvantages include a lack of direct visualization of the surgical site and reduced dexterity of instruments, as compared to traditional open surgeries. Maneuvering surgical instruments with the necessary degree of dexterity for surgical procedures is difficult under these conditions, compounded by the fact that a surgeon often needs to reach off-axis points within a body cavity in the course of minimally invasive procedures. Accordingly, a need exists for a system capable of articulating surgical instrumentation through multiple planes in an internal body cavity with accuracy and precision. It is further desirable to provide a surgeon with a control system that is intuitive and easy to operate to compensate for the lack of direct visualization within a body cavity.
Accordingly, a need exists for a surgical device capable of giving a surgeon control of a surgical instrument in multiple planes of movement.


In the auto precharge circuit, a plurality of read auto precharge signal generating units and a plurality of auto precharge signal output units share a single write auto precharge signal generating unit. Each read auto precharge signal generating unit logically combines an internal CAS command signal, an internal address signal and a pre auto precharge signal to generate an auto precharge detect signal and a read auto precharge signal. The write auto precharge signal generating unit delays the read auto precharge signal by a predetermined time to generate a write auto precharge signal. Each auto precharge signal output unit logically combines the internal CAS command signal, an internal address signal, a read auto precharge signal, and a write auto precharge signal to output an auto precharge signal.

The present invention relates to a semiconductor memory device, and more particularly to a semiconductor memory device capable of reducing the area occupied by an auto precharge circuit.
In a typical semiconductor memory device, the word line is automatically disabled upon completion of a write operation in response to a write command that includes an auto precharge command. The disabling is performed by an auto precharge control circuit included within the semiconductor memory device. When the write command, which includes the auto precharge command, is inputted to the semiconductor memory device, the auto precharge control circuit automatically generates the precharge signal at a predetermined time point after the input operation of the semiconductor memory device is finished. In response to the precharge signal, a row activating unit (or row decoder) disables the word lines belonging to the cells that have finished the write operation.
An auto precharge block is present for each memory bank, and memory bank information is carried in an internal column access strobe command signal (ICAS) that is inputted to the auto precharge block. A time point at which the auto precharge signal is generated depends on whether a signal is a read signal or a write signal. That is, when the signal is a read signal the auto precharge signal is generated just after the read command, whereas when the signal is a write signal the auto precharge signal is generated at variable time points after the write command, since the write recovery time (or tDPL: data in to precharge command; hereinafter, referred to as 'tWR') is required.
The tWR is a period of time ranging from when the data is stored in a unit cell of the memory device until the precharge operation is performed. That is, the tWR is a minimum time period in which data can be sufficiently stored in the active bank without interrupting the precharge command.
In order to secure the tWR, a delay unit is included in the auto precharge block. FIG. 1 shows an embodiment in which a delay unit is included in an auto precharge circuit.
Referring to FIG. 1, the auto precharge circuit 10 includes: a read auto precharge signal generating unit 20, which receives a predetermined predeterminedsignal to generate a read auto precharge signal; a write auto precharge signal generating unit 30, which delays the read auto precharge signal for a predetermined predeterminedtime to generate a write auto precharge signal; and an auto precharge signal output unit 40, which receives the read/write auto precharge signals and outputs an auto precharge signal. The write auto precharge signal generating unit 30 includes a first delay unit 31 shifting the read auto precharge signal such that it is synchronized with the internal clock signal, and a second delay unit 32 that delays the read auto precharge signal for a predetermined predetermined time in accordance with the CAS latency CL.
The read auto precharge signal generating unit 20 receives ICAS<0:3> and IA<10> as inputs. ICAS<0:3> and IA<10> are obtained by converting a CAS command, which consists of an external write or read command, and an address signal address<10>, which determines whether or not the signal is the auto precharge, into internal signals. The internal CAS command ICAS<0:3> includes the bank information contained in the internal signal, and the generated time point varies in accordance with whether the signal is a read or a write signal (shifted 2 clock cycles from the external write signal). Also, the internal address signal IA<10> has its generating time point varied in accordance with whether the signal is a read or a write signal (shifted 2 clock cycles from the external write signal). The above example assumes that the semiconductor device has 4 banks.
Since each memory bank includes an auto precharge circuit 10, when there are 4 banks, four read auto precharge generating units 20, four write auto precharge signal generating units 30, and four auto precharge signal output units 40 are necessary. In a semiconductor device, the circuit area increases as the number of banks increases, and thus cell efficiency decreases.
The block shown in FIG. 1 operates as follows.
In the read auto precharge case, ICAS<0> and IA<10> are generated in response to externally input commands, and ICAS<0> and IA<10> are inputted to the auto precharge signal generating circuit of the designated bank. The read auto precharge signal generating unit 20 holds an auto precharge detect signal APCG_DETB at a low level by a latch operation. The read auto precharge signal Read_APCG<0> of a low level is generated if a burst end signal is received during a burst operation.
It is not necessary to secure the tWR in the read operation, and thus the read auto precharge signal Read_APCG<0> is not inputted to the write auto precharge signal generating unit 30, and is instead directly input to the auto precharge signal output unit 40 where the auto precharge signal APCG<0> is output.
In the write auto precharge case, similar to the read auto precharge, the ICAS<0> and the IA<0> are generated in response to the externally input commands and the signals are then input to the auto precharge signal generating unit 20 of the designated bank. The auto precharge detect signal APCG_DETB maintains the low level by a latch operation, and the read auto precharge signal Read_APCG<0> is generated if the burst end signal is received. However, in the write auto precharge case, the read auto precharge signal Read_APCG<0> must pass through the write auto precharge signal generating unit 30 in order to secure the tWR in the write operation. The write auto precharge signal Write_APCG<0>, which is delayed for tWR through the first and second delay units 31, 32 of the write auto precharge signal generating unit 30 is output from the auto precharge signal generating unit 40 as the auto precharge signal APCG<0>.
The write signal WT is supplied so that only one of the write auto precharge signal and the read auto precharge signal is selected and output.
The write auto precharge signal generating unit 30 shown in FIG. 1 must be formed in each bank even though each write auto precharge signal generating unit 30 has the same structure, resulting in the area of the semiconductor device being unnecessarily large.

Auto precharge circuit sharing a write auto precharge signal generating unit


In a CRT inner resistor, it is intended to prevent the potential of an electrode from being varied owing to leak current that is caused by electric field concentration on the circumferential portion of the electrode because an insulating substrate is charged with stray electrons. An insulating substrate, and electrodes and a resistive body that are connected to each other are provided. An insulating glass layer is provided on the insulating substrate so as to cover the resistive body. Shield members made of insulating glass are provided along the circumferences of the respective electrodes so as to cover the peripheries of the respective electrodes and the portions outside the peripheries of the respective electrodes. The shield members prevent charging of the portions of the insulating substrate outside the peripheries of the respective electrodes and in their vicinities, prevent electric field concentration in the vicinity of the peripheries of the respective electrodes, and inhibit the occurrence of leak current.

The present invention relates to a resistor that is incorporated in a cathode-ray tube (hereinafter referred to as a CRT inner resistor or an inner resistor) and, more particularly, to a CRT inner resistor capable of preventing leak current.
A CRT inner resistor for supplying a prescribed focus voltage and convergence correction voltage is provided in the electron gun portion of a CRT. As shown in FIG. 1A, an inner resistor 6 as mentioned above has an insulating substrate 11, and electrodes 12a-12c and a resistive body 13 that are provided on the insulating substrate 11. The electrodes 12a-12c are provided in series at both ends and a prescribed intermediate position of the resistive body 13. As shown in FIG. 1B, an insulating glass layer 14 is provided on the insulating substrate 11 so as to cover the resistive body 13. The insulating glass layer 14 is to protect the resistive body 13 from the high-voltage environment inside a CRT.
With the inner resistor 6, a prescribed intermediate voltage can be obtained from the electrode 12c that is provided at the prescribed intermediate position of the resistive body 13 by using, as a ground side, the electrode 12a that is connected to one end of the resistive body 13 and supplying a high voltage to the electrode 12b that is connected to the other end of the resistive body 13.
However, the inner resistor having the above structure has the following problems.
In the inside space of a CRT where the inner resistor is disposed, scanning with electron beams is performed by supplying a high voltage of about 20-30 kV. Therefore, stray electrons slightly exist in the vicinity of the inner resistor and cause charging of the surface of the insulating substrate.
However, as shown in FIGS. 2A (enlarged view of the main part) and 2B (sectional view of the main part), the peripheral portions of the respective electrodes 12a-12c (represented by the electrode 12c in those figures) of the inner resistor 6 have what is called a "knife edge" shape in which the film thickness gradually decreases from the central side to the outside because the electrodes 12a-12c are formed on the insulating substrate 11 by screen printing. Therefore, as shown in FIG. 2C, which is an enlarged view of part B of FIG. 2B, an electric field is concentrated in the vicinity of the circumference of the electrode 12c owing to slight charging of the surface of the insulating substrate 11 and the electric field strength is increased there. Electrons are emitted from the circumferential portion of the electrode 12c by field emission and leak current occurs. As a result, the potential of the electrode 12c is varied.
This is a factor of causing problems of mis-focusing due to a variation in focus voltage and a mis-convergence due to a variation in convergence correction voltage.


An image sensor, an electric device using the same and a focusing method of the electric device are provided. The image sensor comprises a plurality of image capturing units and a detecting unit. Each image capturing unit includes an image capturing pixel and a first micro lens. The first micro lens is disposed in front of the image capturing pixel. The detecting unit has a focus detecting pixel and a second micro lens. The second micro lens is disposed in front of the image detecting pixel. A length of the second micro lens is different from a length of the first micro lenses.

1. Technical Field
The disclosure relates in general to a sensor, a device using the same and a processing method of the device, and more particularly to an image sensor, an electric device using the same and a focusing method of the electric device.
2. Description of the Related Art
Along with the development in camera technology, various digital cameras are invented. The digital camera does not need any film, thus the digital camera has been popular in public.
The digital camera includes a sensor chip for receiving the light beams reflected from an object and capturing an image of the object. The image of the object can be recorded forever and can be shown on a display without being print on a photo paper.
In the digital camera, an autofocus process is applied for automatic focusing the image. The accuracy and the time consumption of the autofocus process are important for shooting the image. If the accuracy of the autofocus process is not good, then the image might be obscured. If the time consumption of the autofocus process is large, then the digital camera cannot capture a fast moving object.

Image sensor, electric device using the same and focusing method of the electric device


A data transmission system capable of transmitting data at high speed without being bound by a counterpart's power supply voltage can be realized. The data transmission system comprises multiple electronic equipment having individual power supplies, a cable for connecting between the multiple electronic equipment so as to transmit signals therebetween, digital data transmitting circuits extending between the multiple electronic equipment and the cable and each having an open drain type output section at the transmitting end, and an input section provided with a pull-up type resistor at the receiving end, wherein the resistor and the output section are moved from the electronic equipment to the connector of the cable so that parasitic capacitance for restricting time constant of waveforms of signals when rising is changed from a capacitance to a small capacitance.

A conventional data transmission system as illustrated by a circuit diagram in FIG. 4(A) comprises multiple electronic equipment 10, 20 each provided with an individual power supply, and a cable 30 for connecting therebetween. The data transmission system includes two sets of data transmitting circuits each having an open drain type output section at a transmitting end and an input section provided with a pull-up type resistor at a receiving end, and these data transmitting circuits extend between the electronic equipment 10, 20 and the cable 30. A first digital data transmitting circuit is provided for transmitting data from the electronic equipment 10 to the electronic equipment 20 while a second digital data transmitting circuit is provided for transmitting data from the electronic equipment 20 to the electronic equipment 10 in an opposite direction.
The electronic equipment 10 (first electronic equipment) comprises a power supply 11 of an output voltage Va, an internal circuit 14 for effecting various data processing adaptable to intend applications, a transmitting circuit 12 for subjecting transmission data supplied from the internal circuit 14 to a proper coding processing or modulating processing such as a parallel-serial conversion and the like so as to adjust a data format, an open drain type output section 13 (first output section) for binarizing an output signal from the transmitting circuit 12 and transmitting the binarized output signal to the electronic equipment 20 by way of the cable 30, an input section 16 (second input section) for waveform shaping a binary signal supplied from the electronic equipment 20 by way of the cable 30 and inputting thereto, a pull-up resistor Ra (second resistor) which is attached to the input side of the input section 16, and a receiving circuit 15 for subjecting the received data inputted to the input section 16 to a proper decoding processing or demodulating processing such as serial-parallel conversion and the like so as to adjust a data format and supplying it to the internal circuit 14.
The transmitting circuit 12, the internal circuit 14, the receiving circuit 15, the input section 16 are respectively operated under the output voltage Va while the pull-up resistor Ra is connected to a power supply line of the output voltage Va at one end and also connected to an input line of the input section 16 at the other end so as to perform its function utilizing the output voltage Va. On the other hand, the open drain type output section 13 is employed so as to supply a signal without dependence on the output voltage Va of its own electronic equipment 10. That is, the output section 13 is rendered in a ground state in its output when an output value thereof is low while it is rendered in a high impedance state (floating state, high resistive state) in its output when the output value is high.
The electronic equipment 20 (second electronic equipment) that is a communication counterpart of the electronic equipment 10 comprises a power supply 21 of an output voltage Vb, an internal circuit 24 for effecting various data processing adaptable to intend applications, a transmitting circuit 25 for subjecting transmission data supplied from the internal circuit 24 to a proper coding processing or modulating processing such as a parallel-serial conversion and the like so as to adjust a data format, an open drain type output section 26 (second output section) for binarizing an output signal from the transmitting circuit 25 and transmitting the binarized output signal to the electronic equipment 10 by way of the cable 30, an input section 23 (first input section) for waveform shaping a binary signal supplied from the electronic equipment 10 by way of the cable 30 and inputting thereto, a pull-up resistor Rb (first resistor) which is attached to the input side of the input section 23, and a receiving circuit 22 for subjecting the received data inputted to the input section 23 to a proper decoding processing or demodulating processing such as serial-parallel conversion and the like so as to adjust a data format and supplying it to the internal circuit 24.
The input section 23, the receiving circuit 22, the internal circuit 14 and the transmitting circuit 25 are respectively operated under the output voltage Vb while the pull-up resistor Rb is connected to a power supply line of the output voltage Vb at one end and also connected to an input line of the input section 23 at the other end so as to perform its function utilizing the output voltage Vb. On the other hand, an open drain type output section 26 is employed so as to supply a signal without dependence on the output voltage Vb of its own electronic equipment 20. That is, the output section 26 is rendered in ground state in its output when an output value thereof is low while it is rendered in a high impedance state (floating state, high resistive state) in its output when the output value is high.
The cable 30 has a connector 31 provided at its one end at the electronic equipment 10 side and another connector 32 provided at its other end at the electronic equipment 20 side, and also it has a long intermediate portion which is flexible and soft so that a physical connection between the electronic equipment 10 and electronic equipment 20 can be dynamically and simply established in compliance with the necessity of communication. Multiple signal transmission lines 33, 35 and a ground line 34 which are respectively made of copper wire and the like, and insulatively coated, and built in the cable 30. The lines 33, 34, 35 are respectively connected to corresponding contact terminals of the connector 31 at each one end and also connected to corresponding contact terminals of the connector 32 at each other end. The ground line 34 may be connected to a shield or may act as a shield.
When the electronic equipment 10 and the electronic equipment 20 are connected to each other by the cable 30, the output line of the output section 13, the signal transmission line 33 and the input line of the input section 23 are connected to one another, and the ground line of the electronic equipment 10, the line 34 and the ground line of the electronic equipment 20 are connected to one another while the output line of the output section 26, the line 35 and the input line of the input section 16 are connected to one another. That is, a first digital data transmitting circuit for transmitting a binary signal from the electronic equipment 10 to the electronic equipment 20 is formed of the output section 13, the line 33 and the input section 23, while a second digital data transmitting circuit for transmitting a binary signal from the electronic equipment 20 to the electronic equipment 10 in an opposite direction is formed of the output section 26, the line 35 and the input section 16.
The connector 31 is mounted onto the electronic equipment 10 and the connector 32 is mounted onto the electronic equipment 20, and the electronic equipment 10 and the electronic equipment 20 are connected to each other by the cable 30 so as to transmit data in order to transmit and receive data between the electronic equipment 10, 20. In this state, the transmission of data from the electronic equipment 10 to the electronic equipment 20 is effected by the first digital data transmitting circuit (output section 13→line 33→input section 23), while the transmission of data from the electronic equipment 20 to the electronic equipment 10 is effected by the second digital data transmitting circuit (output section 26→line 35→input section 16).
More in detail, an output state of the output section 13 (or 26) is changed between a ground state and a high impedance state as data value to be transmitted is low or high or ever changed so that the line 33 (or 35) is rendered in the ground state when a low data value is outputted. Such a ground state is inputted to the input section 23 (or 16) so that the low data value is transmitted. On the other hand, when a high data value is outputted, the signal transmission line 33 (or 35) is separated from the ground and is rendered in an output voltage Vb (or Va) application state by way of the pull-up resistor Rb (or Ra) and such a state is inputted to the input section 23 (or 16) so that the high data value is transmitted.
According to the conventional data transmission system, since the open drain type output sections 13, 26 are employed at the transmitting end while the input sections 23, 16 provided with the pull-up resistor Rb, Ra are employed at the receiving end, even if the electronic equipment 10, 20 are provided with individual power supplies 11, 21 and operate by their own power supply voltages Va, Vb, they can be connected to each other so as to transmit data by the cable 30 without being bound by the output voltage Va, Vb of the communication counterpart.
Although line capacitance is intensively illustrated on the lines 33, 35 of the cable 30, a capacitance C which distributes between the ground line 34 and a shield or other coating line or the like is parasitic on the lines 33, 35. The capacitance C has a property to increase substantially in proportion to the lengths of the lines 33, 35, and it is generally considerably larger than the capacitance which is parasitic on each circuit inside equipment. When the signals on the lines 33, 35 are changed from a low state to a high state, they slow down by time constant (resistance Rb×capacitance C), (resistance Ra×capacitance C), in accordance with the combination of the capacitance C, resistors Rb, Ra at rising of the signals.
Accordingly, if the data transmission rate is suitable, it is possible to obtain a signal waveform which clearly shows a binary state (see waveform example at the time of low transmission rate shown in FIG. 4B). If the data transmission rate is increased from the foregoing rate, the signal waveform is collapsed, particularly a high state is not made clear (see the waveform example at the time of high transmission rate shown in FIG. 4C) so that the data is not transmitted accurately, causing a problem that it is difficult to speed up data transmission or increase data transmission rate.
Although various standards and the like capable transmitting data at high speed are proposed and in practical use, the restriction imposed on a cable and a transmitting circuit become severe as the data transmission is speeded up, a driving voltage and other bindings are imposed on a driving condition of the signal transmission line.
Under the circumstances, at present if data is transmitted without being bound by a counterpart's power supply voltage, a transmission rate is restricted, while if data is transmitted by increasing the transmission rate, the data transmission is bound by the counterpart's power supply voltage.
It becomes a technical problem to increase the transmission rate while following an open drain type transmission system adaptable for a different power supply so as to meet both advantages, namely, not to be restricted in transmission rate and not to be bound by the counterpart's power supply voltage.


A first device delivers a clock offset message to a second device. The second device offsets its data transmission according to the clock offset message. A test pattern is transmitted from the second device to the first device. The first device then checks the received test pattern to determine whether the transmission was successful. The first device can then deliver an additional clock offset message to the second device to instruct the second device to offset its data transmission by a different value than was used previously. The second device again transmits the test pattern and the first device again checks the received pattern. By trying a number of clock offset values and determining which values result in successful transmissions of data, the first device can determine the optimal clock offset value and instruct the second device to use this value for all transmissions.

One important element in designing today's computer systems is minimizing channel error (errors occurring during data transfers) on multi-drop busses. Multi-drop busses typically connect one device to two or more other devices. Impedance discontinuities along the bus can create a standing wave on a clock signal, thereby degrading clock signal integrity and skewing the clock signal with respect to data signals. This skew may result in a master device latching data from a slave device at a time other than an optimal time, and increased channel error results.
Prior techniques for dealing with clock skew introduced by impedance discontinuities include reducing the maximum allowable clock frequency on the bus to ensure that valid data is latched at the receiving device. Of course, a reduction in clock frequency results in decreased bus performance, and is therefore undesirable.

Method and apparatus for optimizing timing for a multi-drop bus


According to the method of preventing the corrosion of metallic wirings of the present invention, aluminium alloy wirings are formed on the surface of a substrate with the use of photoresists, and the photoresists are then removed. Thereafter, HMDS (hexamethyl disilazine) serving as a surface-active agent or its derivative is supplied to the aluminium alloy wirings to form hydrophobic molecular layers on the lateral walls of the aluminium alloy wirings.

The present invention relates to a method of preventing the corrosion of metallic wirings for LSIs or the like formed on the surface of a substrate.
As the material of metallic wirings for LSIs or the like, there may be used a single-layer film comprising aluminium., refractory metal (titanium, titanium nitride, tungusten, titanium tungusten) or an aluminium alloy (containing about 1% of silicon and about 0.5% of copper), or a multi-layer film comprising an aluminium alloy and refractory metal.
Such metallic wirings are formed by etching a metallic film formed on a silicon oxide, for example, a metallic film containing aluminium, with chlorine-containing gas such as BCl.sub.3, SiCl.sub.4, Cl.sub.2 or CHCl.sub.3. The reason why the chlorine-containing gas is used, is because an aluminium chloride (AlCl.sub.3) which is a compound of aluminium and chlorine, presents the highest vapor pressure among compounds of aluminium with fluorine, chlorine, bromine, iodine or the like.
FIGS. 7 (a) to (c) show conventional dry-etching steps with an aluminium alloy used as the material of metallic wirings.
As shown in FIG. 7 (a), a silicon oxide film containing boron and phosphorus (hereinafter referred to as BPSG film) 2 is formed on a substrate 1, an aluminium alloy film 3 is then formed on the BPSG film 2 and photoresists 4 are then formed on the aluminium alloy film 3. More specifically, the BPSG film 2 is deposited by a thickness of 700 nm on the substrate 1 by a chemical vapor deposition method (hereinafter referred to as CVD method). Then, there is deposited, by a thickness of 800 nm, the aluminium alloy film 3 comprising an aluminium alloy containing 1% of silicon and 0.5% of copper (hereinafter referred to as Al-Si(1%)-Cu(0.5%)) by a sputtering method. Applied to the aluminium alloy film 3 is a resist film, which is then subjected to photolithography to form the photoresists 4 in a desired pattern.
As shown in FIG. 7 (b), with the photoresists 4 serving as masks, the aluminium alloy film 3 is etched by a reactive ion etching method with the use of chlorine-containing gas such as SiCl.sub.4, Cl.sub.2, CHCl.sub.3 or the like, thus forming aluminium alloy wirings 5 in a desired pattern. At this time, a great amount of chlorine-containing substances 6 comprising residual chlorine and a chloride such as AlCl.sub.3 and the like, sticks to the lateral walls of the photoresists 4 and the aluminium alloy wirings 5. If the substrate 1 is taken out in the air with no surface treatment applied to the aluminium alloy wirings 5 after completion of the etching, there is a likelihood that the chlorine-containing substances 6 sticking to the photoresists 4 and the aluminium alloy wirings 5 are reacted with water content in the air to cause the aluminium alloy wirings 5 to be corroded. Such corrosion may result in serious troubles such as disconnection of the aluminium alloy wirings and decreased reliability of the semiconductor devices.
In a conventional method, upon completion of the etching of the aluminium alloy film 3, the substrate 1 has been conveyed into another chamber without the aluminium alloy wirings 5 exposed to the air. After the photoresists 4 to which a great amount of residual chlorine and a chloride sticks, and major portions of the chlorine-containing substances 6 sticking to the lateral walls of the aluminium alloy wirings 5, had been removed by oxygen plasma in the chamber above-mentioned, the substrate 1 has been taken out in the air, as shown in FIG. 7 (c).
In the method using the oxygen plasma above-mentioned, however, the corrosion of the aluminium alloy wirings has not been perfectly prevented. More specifically, according to the method using the oxygen plasma, the photoresists 4 and a major portion of the chlorine-containing substance 6 sticking to the surface of the substrate 1 have been removed, but chlorine atoms entered in the grain boundary of the aluminium alloy wirings 5 could not been removed and have reacted with water content in the air.

Method of preventing the corrosion of metallic wirings

Matsushita Electric Industrial Co., Ltd.