This invention relates to nucleoside, nucleotide, and oligonucleotide analogs that incorporate non-standard nucleobase analogs, defined to be those that present a pattern of hydrogen bonds to a paired nucleobase analog in a complementary strand that is different from the pattern presented by adenine, guanine, cytosine, and thymine. The invention is specifically concerned with compositions of matter that present the donor-donor-acceptor, donor-acceptor-donor, and acceptor-donor-donor non-standard hydrogen bonding patterns on pyrimidine analogs, where nucleoside analogs bearing these pyrimidine analogs do not epimerize as easily as those known in the art. The heterocycles on these nucleoside analogs are diaminopyridines and aminopyridones that have electron withdrawing groups attached to the position analogous to the 5-position of the ring in standard pyrimidines, including nitro, cyano, and carboxylic acid derivatives.

Natural oligonucleotides bind to complementary oligonucleotides according to the well-known rules of nucleobase pairing first elaborated by Watson and Crick in 1953, where adenine (A) pairs with thymine (T) (or uracil, U, in RNA), and guanine (G) pairs with cytosine (C), with the complementary strands anti-parallel to one another. In this disclosure, "DNA" or "nucleic acid" is understood to include, as appropriate, both DNA (where the sugar is 2′-deoxyribose) and RNA (where the sugar is ribose), as well as derivatives where the sugar is modified, as in 2′—O-methyl, 2′-O-allyl, 2′-deoxy-2′-fluoro, and 2′,3′-dideoxynucleoside derivatives, nucleic acid analogs based on other sugar backbones, such as threose, locked nucleic acid derivatives, bicyclo sugars, or hexose, glycerol and glycol sugars [Zhang, L., Peritz, A., Meggers, E. (2005) A simple glycol nucleic acid. J. Am. Chem. Soc. 127, 4174-4175], nucleic acid analogs based on non-ionic backbones, such as "peptide nucleic acids", these nucleic acids and their analogs in non-linear topologies, including as dendrimers, comb-structures, and nanostructures, and these nucleic acids and their analogs carrying tags (e.g., fluorescent, functionalized, or binding) to the ends, sugars, or nucleobases.
These pairing rules allow for the specific hybridization of an oligonucleotide to a complementary oligonucleotide, making oligonucleotides valuable as probes in the laboratory, in diagnostic applications, as messages that can direct the synthesis of specific proteins, and in a wide range of other applications well known in the art. Such base pairing is used, for examples and without limitation, to capture other oligonucleotides to beads, arrays, and other solid supports, to allow nucleic acids to fold in hairpins, beacons, and catalysts, as supports for functionality, such as fluorescence, fluorescence quenching, binding/capture tags, and catalytic functionality, as part of more complex architectures, including dendrimers and nanostructures, and as scaffolds to guide chemical reactions.
Further, nucleobase pairing is the basis by which enzymes are able to catalyze the synthesis of new oligonucleotides that are complementary to template nucleotides. In this synthesis, building blocks (normally the triphosphates of ribo- or deoxyribonucleosides carrying of A, T, U, C, or G) are directed by a template oligonucleotide to form a complementary oligonucleotide with the complementary sequence. This process is the basis for replication of all forms of life, and also serves as the basis for technologies for enzymatic synthesis and amplification of specific heterosequence nucleic acids by enzymes such as DNA and RNA polymerase, in the polymerase chain reaction (PCR), and in a variety of architectures that may involve synthesis, ligation, cleavage, immobilization and release, inter alia, used in technology to detect nucleic acids.
Nucleobase pairing following rules of complementarity is known to be useful in a variety of architectures. In solution, nucleobase pairing in the loop of a molecular beacon can open the beacon, separating a fluorescent species attached to one end of a hairpin structure from a quencher on the other. Pairing can assemble two DNA fragments transiently or covalently, as in a template-directed ligation. Pairing is useful for affixing an oligonucleotide that is free in solution to a support carrying the complementary oligonucleotide. The oligonucleotide can carry functional groups, including fluorescent groups attached to the nucleobases.
The Watson-Crick pairing rules can be understood chemically in terms of the arrangement of hydrogen bonding groups on the heterocyclic nucleobases of the oligonucleotide, groups that can either be hydrogen bond donors or acceptors. In the standard Watson-Crick geometry, a large purine nucleobase pairs with a small pyrimidine nucleobase. Thus, the AT nucleobase pair is the same size as a GC nucleobase pair. This means that the rungs of the DNA ladder, formed from either AT or GC nucleobase pairs, all have the same length.
Further recognition between nucleobases is determined by hydrogen bonds between the nucleobases. In standard nucleobases, hydrogen bond donors are heteroatoms (nitrogen or oxygen in the natural nucleobases) bearing a hydrogen; hydrogen bond acceptors are heteroatoms (nitrogen or oxygen in the natural nucleobases) with a lone pair of electrons. In the geometry of the Watson-Crick nucleobase pair, a six membered ring (in standard nucleobases, a pyrimidine) is juxtaposed to a ring system composed of a fused six membered ring and a five membered ring (in standard nucleobases, a purine), with a middle hydrogen bond linking two ring atoms, and hydrogen bonds on either side joining functional groups appended to each of the rings, with donor groups paired with acceptor groups.
In many applications, the nucleobases incorporated into one or more oligonucleotide analogs carry an appendage. In standard nucleobases, the appendage, or side chain, is attached to one or more pyrimidines at the 5-position, or at the 7-position of a 7-deazapurine, or to an exocyclic nitrogen, most often the exocyclic amino group of adenine or cytosine. Such nucleoside analogs have application because of their combination of Watson-Crick nucleobase pairing ability and the properties or reactivities associated with species appended via the side chain. For example, oligonucleotides containing a T to which is appended a side chain bearing a biotin residue can first bind to a complementary oligonucleotide, and the hybrid can then be isolated by virtue of the specific affinity of biotin to avidin [Langer, P. R.; Waldrop, A. A.; Ward, D. C. (1981) Proc. Nat. Aced. Sci. 78, 6633-6637]. This finds application in diagnostic work. Instead of biotin, the side chain can carry a fluorescent moiety, or a moiety that quenches the fluorescence of another moiety, a branching point, or a moiety that complexes to a metal, or a moiety that confers catalytic activity on the oligonucleotide, or a moiety that assists in the attachment of the oligonucleotide analog to a solid support, such as a bead, a one dimensional array, or a two dimensional array.
Often, derivatized standard nucleotides can be incorporated into oligonucleotides by enzymatic transcription of natural oligonucleotide templates in the presence of the triphosphate of the derivatized nucleoside, the substrate of the appropriate (DNA or RNA) polymerase, or a reverse transcriptase. In this process, a natural nucleoside is placed in the template, and standard Watson-Crick nucleobase pairing is exploited to direct the incoming modified nucleoside opposite to it in the growing oligonucleotide chain.
The standard available nucleobase pairs are limited in that they make available only two mutually exclusive hydrogen bonding patterns. This means that should one wish to introduce a modified nucleoside based on one of the natural nucleosides into an oligonucleotide, it would be incorporated wherever the complementary natural nucleoside is found in the template. For many applications, this is undesirable.
Further, in many applications, it would be desirable to have nucleobase pairs that behave as predictably as the AT (or U) and GC nucleobase pairs, but that do not cross-pair with natural oligonucleotides, which are built from A, T (or U), G, and C. This is especially true in diagnostics assays based. Biological samples generally contain many nucleic acid molecules in addition to the nucleic acid that one wishes to detect. The adventitious DNA/RNA, often present in abundance over the targeted analyte DNA (or RNA), is also composed of A, T (or U), G, and C. Thus, adventitious DNA/RNA can compete with the desired interactions between two or more oligonucleotide-like molecules.
Many of the limitations that arise from the existence of only four standard nucleobases, joined in only two types of nucleobase pairs via only two types of hydrogen bonding schemes, could be overcome were additional nucleobases available that could be incorporated into oligonucleotides. Here, the additional nucleobases would still pair in the Watson-Crick geometry, but would present patterns of hydrogen bond donating and accepting groups in a pattern different from those presented by the natural nucleobases. They therefore would form nucleobase pairs with additional complementary nucleobases in preference to (and, preferably, with strong preference to, meaning with at least a 10 to 100 fold affinity greater than to mismatched oligonucleotides or oligonucleotide analogs). In the last decade, Benner disclosed compositions of matter that were intended to overcome the limitations of molecular recognition by changing the pattern of hydrogen bond donor and acceptor groups presented by a nucleobase to the nucleobase on a complementary oligonucleotide analog [U.S. Pat. Nos. 5,432,272, 5,965,364, 6,001,983, 6,037,120, 6,140,496, 6,627,456, 6,617,106]. These disclosures showed that the geometry of the Watson-Crick nucleobase pair can accommodate as many as 12 nucleobases forming 6 mutually exclusive pairs. Of these, four nucleobases forming two pairs are "standard", while eight nucleobases forming four pairs were termed "non-standard". Adding the non-standard nucleobases to the standard nucleobases yielded an Artificially Expanded Genetic Information System (AEGIS). Specifically, the structures shown in FIG. 1, taken from U.S. Pat. No. 6,140,496, implement the designated hydrogen bonding patterns. It was also noted that these nucleobases analogs might be functionalized to enable a single biopolymer capable of both genetics and catalysis. Expanded genetic alphabets have now been further explored in a variety of laboratories, and the possibility of a fully artificial genetic system has been advanced [Switzer, C. Y., Moroney, S. E., Benner, S. A. (1989) Enzymatic incorporation of a new base pair into DNA and RNA. J. Am. Chem. Soc. 111, 8322-8323][Piccirilli, J. A., Krauch, T., Moroney, S. E., Benner, S. A. (1990) Extending the genetic alphabet. Enzymatic incorporation of a new base pair into DNA and RNA. Nature 343, 33-37][Piccirilli, J. A., Krauch, I., MacPherson, L. J., Benner, S. A. (1991) A direct route to 3-(ribofuranosyl)-pyridine nucleosides. Helv. Chim. Acta 74, 397-406] [Voegel, J. J., Altorfer, M. M., Benner, S. A. (1993) The donor-acceptor-acceptor purine analog. Transformation of 5-aza-7-deaza-isoguanine to 2′-deoxy-5-aza-7-deaza-iso-guanosine using purine nucleoside phosphorylase. Helv. Chim Acta 76, 2061-2069] [Voegel, J. J., von Krosigk, U., Benner, S. A. (1993) Synthesis and tautomeric equilibrium of 6-amino-5-benzyl-3-methylpyrazin-2-one. An acceptor-donor-donor nucleoside base analog. J. Org. Chem. 58, 7542-7547][Heeb, N. V., Benner, S. A. (1994) Guanosine derivatives bearing an N2-3-imidazolepropionic acid. Tetrahedron Lett. 35, 3045-3048] [Voegel, J. J., Benner, S. A. (1994) Non-standard hydrogen bonding in duplex oligonucleotides. The base pair between an acceptor-donor-donor pyrimidine analog and a donor-acceptor-acceptor purine analog. J. Am. Chem. Soc. 116, 6929-6930][von Krosigk, U., Benner, S. A. (1995) pH-independent triple helix formation by an oligonucleotide containing a pyrazine donor-donor-acceptor base. J. Am. Chem. Soc. 117, 5361-5362][Voegel, J. J., Benner, S. A. (1996) Synthesis, molecular recognition and enzymology of oligonucleotides containing the non-standard base pair between 5-aza-7-deaza-iso-guanine and 6-amino-3-methylpyrazin-2-one, a donor-acceptor-acceptor purine analog and an acceptor-donor-donor pyrimidine analog. Helv. Chim. Acta 79, 1881-1898] [Voegel, J. J., Benner, S. A. (1996) Synthesis and characterization of non-standard nucleosides and nucleotides bearing the acceptor-donor-donor pyrimidine analog 6-amino-3-methylpyrazin-2-one. Helv. Chim. Acta 79, 1863-1880][Kodra, J., Benner, S. A. (1997) Synthesis of an N-alkyl derivative of 2′-deoxyisoguanosine. Syn. Lett., 939-940] [Jurczyk, S., Kodra, J. T., Rozzell, J. D., Jr., Benner, S. A., Battersby, T. R. (1998) Synthesis of oligonucleotides containing 2′-deoxyisoguanosine and 2′-deoxy-5-methyliso-cytidine using phosphoramidite chemistry. Helv. Chim. Acta 81, 793-811][Lutz, S., Burgstaller, P., Benner, S. A. (1999) An in vitro screening technique for polymerases that can incorporate modified nucleotides. Pseudouridine as a substrate for thermostable polymerases. Nucl. Acids Res. 27, 2792-2798][Jurczyk, S. C., Battersby, T. R., Kodra, J. T., Park, J.-H., Benner, S. A. (1999) Synthesis of 2′-deoxyisoguanosine triphosphate and 2′-deoxy-5-methyl-isocytidine triphosphate. Helv. Chim. Acta. 82, 1005-1015] [Jurczyk, S. C., Horlacher, J., Devine, K. G., Benner, S. A., Battersby, I. R. (2000) Synthesis and characterization of oligonucleotides containing 2′-deoxyxanthosine using phosphoramidite chemistry. Helv. Chim. Acta 83, 1517-1524][Rao, P., Benner, S. A. (2001) A fluorescent charge-neutral analog of xanthosine: Synthesis of a 2′-deoxyribonucleoside bearing a 5-aza-7-deazaxanthine base. J. Org. Chem. 66, 5012-50151.
To systematize the nomenclature for the hydrogen bonding patterns, the hydrogen bonding pattern implemented on a small component of a nucleobase pair pare designated by the prefix "py". Following this prefix is the order, from the major groove to the minor groove, of hydrogen bond acceptor (A) and donor (D) groups. Thus, both thymine and uracil implement the standard hydrogen bonding pattern pyADA. The standard nucleobase cytosine implements the standard hydrogen bonding pattern pyDAA. Hydrogen bonding patterns implemented on the large component of the nucleobase pair are designated by the prefix "pu". Again following the prefix, the hydrogen bond donor and acceptor groups are designated, from the major to the minor grooves, using "A" and "D". Thus, the standard nucleobases adenine and guanine implement the standard hydrogen bonding patterns puDA- and puADD respectively.
A central teaching of this disclosure is that hydrogen bonding pattern designated using this systematic nomenclature is distinct, in concept, from the organic molecule that is used to implement the hydrogen bonding pattern. Thus, guanosine is a nucleoside that implements the puADD hydrogen bonding pattern. So does, however, 7-deazaguanosine, 3-deazaguanosine, 3,7-dideazaguanosine, and any of any number of other purines and purine derivatives, including those that carry side chains to which are appended functional groups, such as fluorescent, fluorescent quencher, attachment, or metal complexing groups. Which organic molecule is chosen to implement a specific hydrogen bonding pattern determines, in large part, the utility of the non-standard hydrogen bonding pattern, in various applications to which it might be applied.
The structures disclosed by U.S. Pat. No. 6,140,496, as well as its predecessor patents, provide for an expanded molecular recognition system by providing more than four independently recognizable building blocks that can be incorporated into DNA and RNA.
Should the additional nucleobase pairs be placed into DNA and RNA, and if once so placed they have the desirable pairing properties, chemical stability, and other features known to those skilled in they art, they could be useful for a variety of purposes. For example, RNA molecules prepared by transcription, although it is known to be a catalyst under special circumstances [Cech, T. R.; Bass, B. L (1986). Ann. Rev. Biochem. 55, 599][Szostak, J. W. (1986) Nature 332, 83. Been, M. D.; Cech, T. R. (1988) Science 239, 1412], appear to have a much smaller catalytic potential than proteins because they lack building blocks bearing functional groups. Conversely, the limited functionality present on natural oligonucleotides constrains the chemist attempting to design catalytically active RNA molecules, in particular, RNA molecules that catalyze the template-directed polymerization of RNA.
Likewise, additional nucleobase pairs can be incorporated enzymatically at specific positions in an oligonucleotide molecule [Switzer, C. Y, Moroney, S. E., Benner, S. A. (1989) J. Am. Chem. Soc. 111, 8322]. If functionalized, such additional nucleobases should also allow the incorporation of functional groups into specific positions in a DNA or RNA sequence. A polymerase chain reaction has been demonstrated using a variant of an HIV reverse transcriptase to incorporate the pair between 2,4-diamino-5-(1′-beta-D-2′-deoxyribofuranosyl)-pyrimidine, implementing the pyDAD hydrogen bonding pattern, and 3,9-dihydro-9-(1′-beta-D-2′-deoxyribofuranosyl)-1H-purine-2,6-dione, implementing the puADA hydrogen bonding pattern [Sismour, A. M., Lutz, S., Park, J.-H., Lutz, M. J., Boyer, P. L., Hughes, S. H., Benner, S. A. (2004) PCR amplification of DNA containing non-standard base pairs by variants of reverse transcriptase from human immunodeficiency virus-1. Nucl. Acids. Res. 32, 728-735]. As standard nucleobases bearing functional groups at the 5-position of the uridine ring are accepted as substrates for most polymerases [Leary, J. L., Brigati, D. J., Ward, D. C. (1983) Proc. Natl. Acad. Sci. 80, 4045], non-standard nucleobases that are modified at the analogous positions are also accepted, provided that the polymerase accepts the parent non-standard nucleobase. New nucleobase pairs should also find use in studies of the structure of biologically important RNA and DNA molecules [Chen, T. R., Churchill, M. E. A. Tullius, T. D. Kallenbach, N. R., Seemann, N. C. (1988) Biochem. 27, 6032] and protein-nucleic acid interactions. They should also be useful in assembling nanostructures, including branched DNA useful for diagnostics, or for nanomachines. Further, non-standard nucleobases can be used to expand the genetic code, increasing the number of amino acids that can be incorporated translationally into proteins [Bain, J. D., Chamberlin, A. R., Switzer, C. Y., Benner, S. A. (1992) Ribosome-mediated incorporation of non-standard amino acids into a peptide through expansion of the genetic code. Nature 356, 537-539].
Some commercial applications have already been realized with the expanded genetic information systems disclosed by Benner in his patents. For example, the nucleobase pair between 2-amino-5-methyl]-(1′-beta-D-2′-deoxyribofuranosyl)-4(1H)-pyrimidinone, also known as 2′-deoxyisocytidine, disoC, or sometimes (less correctly) isoC and implementing the pyAAD hydrogen bonding pattern, and 6-amino-1,9-dihydro-9-(1′-beta-D-2′-deoxyribofuranosyl)-3H-purin-2-one, also known as 2′-deoxyisoguanosine, disoG, or sometimes (less correctly) isoG, and implementing the puDDA hydrogen bonding pattern, is incorporated into the branched DNA diagnostics tools marketed today by Bayer. Here, it provides molecular recognition on demand in aqueous solution, similar to nucleic acids but with a coding system that is orthogonal to the system in DNA and RNA. Thus, it prevents the assembly of the branched dendrimer in the assay from being inhibited by adventitious nucleic acid, and prevents adventitious nucleic acid from capturing signaling elements form the nanostructure in the absence of the target analyte nucleic acid, creating noise. Further, adding extra letters to the genetic alphabet speeds hybridization, presumably because it decreases the number of close mismatches where DNA dwells before finding its correct, fully matched partner. The branched DNA assay now has FDA-approval, and is widely used to provide personalized patient care in the clinic.
The Benner patents claimed a wide range of structures generally, but only a few specifically. The compounds specifically claimed, where those claims were supported by specific examples in the disclosure, were disclosed as the preferred implementations of the individual hydrogen bonding patterns, and are reproduced in FIG. 1 (taken from FIG. 2 of U.S. Pat. No. 6,140,496). Making reference to U.S. Pat. No. 6,140,496, the following implementations (where a systematic name is given for the 2′-deoxyribonucleoside; the corresponding ribonucleosides, 2′-O-methyl ribonucleosides, and various derivatives of these were also disclosed) were preferred as implementations for each of the hydrogen bonding patterns:    For the pyDAD hydrogen bonding pattern. The preferred embodiment disclosed in U.S. Pat. No. 6,140,496 supported the pyDAD hydrogen bonding pattern on the 2,4-diaminopyrimidine heterocycle. The specific deoxyribonucleoside was 2,4-diamino-5-(1′-beta-D-2′-deoxyribofuranosyl)-pyrimidine, also named (1R)-1,4-anhydro-2-deoxy-1-C-(2,4-diamino-5-pyrimidinyl)-D-erythropentitol.    For the puADA hydrogen bonding pattern. The preferred embodiment disclosed in U.S. Pat. No. 6,140,496 supported the pyDAD hydrogen bonding pattern on the xanthine heterocycle. The specific deoxyribonucleoside was 3,9-dihydro-9-(1′-beta-D-2′-deoxyribofuranosyl)-1H-purine-2,6-dione, also known as 9-(2′-deoxy-beta-D-ribosyl)-xanthine.    For the pyAAD hydrogen bonding pattern. The preferred embodiment disclosed in U.S. Pat. No. 6,140,496 supported the pyDAD hydrogen bonding pattern on the 5-methyl-isocytosine heterocycle. The specific deoxyribonucleoside was 2-amino-5-methyl-1-(1′-beta-D-2′-deoxyribofuranosyl)-4(1H)-pyrimidinone,    For the puDDA hydrogen bonding pattern. The preferred embodiment disclosed in U.S. Pat. No. 6,140,496 supported the pyDAD hydrogen bonding pattern on the isoguanine heterocycle. The specific deoxyribonucleoside was 6-amino-1,9-dihydro-9-(1′-beta-D-2′-deoxyribofuranosyl)-3H-purin-2-one.    For the pyDDA hydrogen bonding pattern. The preferred embodiment disclosed in U.S. Pat. No. 6,140,496 supported the pyDAD hydrogen bonding pattern on the 6-amino-5-methyl-2(1H)-pyrazinone heterocycle. The specific deoxyribonucleoside was 6-amino-5-methyl-3-(1′-beta-D-2′-deoxyribofuranosyl)-2(1H)-pyrazinone.    For the puAAD hydrogen bonding pattern. The preferred embodiment disclosed in U.S. Pat. No. 6,140,496 supported the pyDAD hydrogen bonding pattern on the 5-aza-3,7-dideazaguanosine heterocycle. The specific deoxyribonucleoside was 2-amino-1,9-dihydro-5-aza-3,7-dideaza-9-(1′-beta-D-2′-deoxyribofuranosyl)-1H-purin-6-one, also known as 7-amino-9-(1′-beta-D-2′-deoxyribofuranosyl)-imidazo[1,2-c]pyrimidin-5(1H)-one,    For the pyADD hydrogen bonding pattern. The preferred embodiment disclosed in U.S. Pat. No. 6,140,496 supported the pyDAD hydrogen bonding pattern on the 6-amino-3-methyl-2(1H)-pyrazinone heterocycle. The specific deoxyribonucleoside was 6-amino-3-methyl-5-(1′-beta-D-2′-deoxyribofuranosyl)-2(1H)-pyrazinone,    For the puDAA hydrogen bonding pattern. The preferred embodiment disclosed in U.S. Pat. No. 6,140,496 supported the pyDAD hydrogen bonding pattern on the 4-amino-1,3,5-triazin-2(8H)-one heterocycle. The specific deoxyribonucleoside was 4-amino-8-(2-deoxy-beta-D-erythro-pentofuranosyl)-imidazo[1,2-a]-1,3,5-triazin-2(8H)-one, also known as, 4-amino-8-(1′-beta-D-2′-deoxyribofuranosyl)-imidazo[1,2-a]-1,3,5-triazin-2(8H)-one.
Despite the value of the compositions disclosed by U.S. Pat. No. 6,140,496, it is clear that the specific compositions used to implement the various non-standard hydrogen bonding patterns were not optimal, at least from the perspective of potential utility. Several problematic physical and chemical properties of the compositions that were claimed specifically were disclosed in the specification of U.S. Pat. No. 6,140,496.
For example, the nucleobases that were, in U.S. Pat. No. 6,140,496, specifically disclosed as implementations of the pyADD and pyDDA hydrogen bonding patterns undergo an epimerization reaction that interconverts the beta and alpha anomers [von Krosigk, U., Benner, S. A. (1995) pH-independent triple helix formation by an oligonucleotide containing a pyrazine donor-donor-acceptor base. J. Am. Chem. Soc. 117, 5361-5362] [Vogel, J. J., von Krosigk, U. Benner, S. A. (1993) Synthesis and tautomeric equilibrium of 6-amino-5-benzyl-3-methylpyrazin-2-one. An acceptor-donor-donor nucleoside base analog. J. Org. Chem. 58, 7542-7547]. This is illustrated in FIG. 2.
It was noted that this epimerization diminished the utility of these nucleobases. U.S. Pat. No. 6,140,496 and its predecessors proposed to solve the epimerization problem by replacing the furanose ring system (which includes an oxygen in a ring) with a carbocyclic cyclopentane derivative (which does not, and therefore cannot epimerize). The carbocyclic nucleoside analog is, however, difficult to synthesize, and has other disadvantages, and has never been incorporated into a commercial product.
An alternative tactic proposed to manage the epimerization problem has the pyrazine heterocycles that were the preferred implementations of the pyDDA and pyADD hydrogen bonding implementations (respectively) attached to a ribose derivative where a lower alkyl, most preferably methyl, group is attached to the 2′-oxygen. The 2′-O-alkyl group is large, and it was proposed that although the undesired epimerization reaction interconverting the beta and alpha anomers would still occur, steric factors would cause the beta (desired) form to predominate at equilibrium. Again, this would create problems if multiple non-standard nucleobases implementing this hydrogen bonding pattern were incorporated into an oligonucleotide analog.
The specification of U.S. Pat. No. 6,140,496 and its predecessors, as well as the literature, disclose difficulties with the use of 6-amino-1,9-dihydro-9-(1′-beta-D-2′-deoxyribofuranosyl)-3H-purin-2-one (isoguanosine, or isoG) as the implementation of the puDDA hydrogen bonding pattern. In its major keto form, isoguanosine implements the desired puDDA hydrogen bonding pattern. Isoguanosine has long been known to exist, to about 10% of the total in water, in a minor enolic tautomeric form. The enolic tautomer presents the puDAD hydrogen bonding pattern that is complementary to the thymidine and uridine nucleobases. That is, about 10% of isoguanine presents the puDAD hydrogen bonding pattern, not the desired puDDA pattern. This was noted in this specification to inconvenience efforts to use polymerases to copy DNA molecules containing isoguanine-containing nucleotide units. Indeed, some polymerases prefer to place thymidine (T) and/or uridine (U), rather than isocytidine (isoC), opposite isoguanosine in a template. The disutility of this was recently shown by Johnson et al. [Johnson, S. C., Sherrill, C. B., Marshall, D. J., Moser, M. J., Prudent, J. R. (2004) A third base pair for the polymerase chain reaction: inserting isoC and isoG. Nucl. Acids Res. 32, 1937-1941], who attempted to do a polymerase chain reaction amplification of a DNA molecule, requiring the repeated copying of the isoguanine-isocytosine nucleobase pair implementing the puDDA-pyAAD hydrogen bonding patterns. As expected from the known tautomeric behavior of isoguanine, the isoG-isoC pair was lost during the PCR reaction, presumably due to mismatching between T and the minor tautomer of isoguanosine.
Other features of the compounds that were specifically disclosed in U.S. Pat. No. 6,140,496 and its predecessors as the preferred implementations of the various hydrogen bonding schemes narrow the scope of their utility. For example, the heterocycle of 3,9-dihydro-9-(1′-beta-D-2′-deoxyribofuranosyl)-1H-purine-2,6-dione heterocycle (xanthine) proposed to implement the puADA hydrogen bonding pattern, is an acid, having a pKa between 5 and 6. Thus, at neutral pH and higher, where many polymerases operate and where many applications of oligonucleotide analog recognition are desired, xanthine is deprotonated. Deprotonation creates a negative charge, which destabilizes the duplex structure [Geyer, C. R., Battersby, T. R., Benner, S. A. (2003) Nucleobase pairing in expanded Watson-Crick like genetic information systems. The nucleobases. Structure 11, 1485-1498]. It is considered unlikely that multiple xanthines in an oligonucleotide analog would support rule-based molecular recognition effectively.
Likewise, the 2,4-diamino-5-(1′-beta-D-2′-deoxyribofuranosyl)-pyrimidine proposed to implement the pyDAD hydrogen bonding pattern carries a positive charge at pH 7.0, as it is a relatively good base. Further, the synthesis of the 2′-deoxyribonucleoside bearing this nucleobase is long and expensive.
Likewise, the specifically disclosed nucleoside analogs that implement the puAAD hydrogen bonding pattern on the 5-aza-3,7-dideazaguanosine heterocycle may be poor substrates for many DNA and RNA polymerases, especially those that make contact to an unshared pair of electrons in the minor groove [Steitz, T. in Burnett, R. M. and Vogel, H. J. (eds.) Biological Organization: Macromolecular Interactions at High Resolution; Academic Press: New York, 1987, pp. 45-55.]. This limits the utility of triphosphates of nucleoside analogs bearing this heterocycle as a substrate for a DNA polymerase, an RNA polymerase, and reverse transcriptases, as well as the utility of oligonucleotide analogs carrying this heterocycle as templates for these enzymes. This is also the case for derivatives which attach an alkyl group to the N-3 of the purine or purine analogs (in the analogous positions). In U.S. Pat. No. 6,140,496 and its predecessors, various N-3 methylated purines are disclosed as implementations of various hydrogen bonding patterns.
Likewise, the implementation of the pyAAD hydrogen bonding pattern using 5-alkylisocytidinc derivatives proves to present difficulties. Deoxyribosides bearing the 2-amino-5-methyl-1-(1′-beta-D-2′-deoxyribofuranosyl)-4(1H)-pyrimidinone (also know as 5-methylisocytosine) is sensitive to depyrimidinylation, the cleavage of the 1-1′ nitrogen-carbon bond to separate the heterocycle from the sugar, under acidic conditions. Considerable effort was devoted to developing the delicate synthetic procedures needed to prepare oligonucleotide analogs that contain multiple 2-deoxyisocytidines, increasing the expense of the synthesis. The acid sensitivity extends to the oligonucleotides in solution, diminishing their utility.
One purpose of the instant disclosure is to provide nucleobase analogs (where "nucleobase" refers to the heterocycle, or aglycone) that implement non-standard hydrogen bonding patterns, said analogs having properties improved over those analogs of the prior art that implement their respective hydrogen bonding patterns. In particular, the compositions of the instant invention mitigate or avoid entirely the limitations listed above of the compositions that were disclosed in U.S. Pat. No. 6,140,496.
One of ordinary skill in the art would find these improved properties unexpected, even in the light of the disclosures in patents and other literature of the prior art, and that find unexpected the greater utility that these nucleobase analogs have compared to the compositions disclosed in the prior art to implement this hydrogen bonding pattern.
Another purpose of the instant disclosure is to provide nucleoside analogs (where "nucleoside analog" is an analog of the heterocycle together with the sugar or sugar analog) that carry the nonstandard nucleobase analog, where the sugar is 2′-deoxyribose or ribose, as well as analogs where the sugar is modified, as in 2′-O-methyl, 2′-O-allyl, 2′-deoxy-2′-fluoro, and 2′,3′-dideoxynucleoside derivatives, as well as nucleoside analogs based on other sugar backbones, such as threose, locked nucleic acid derivatives, bicyclo sugars, or hexose, glycerol and glycol sugars [Zhang, L., Peritz, A., Meggers, E. (2005) A simple glycol nucleic acid. J. Am. Chem. Soc. 127, 4174-4175].
Another purpose of the instant invention is to provide oligonucleotide analogs that incorporate one or more of the nonstandard nucleoside analogs. These include nucleic acid analogs that incorporate the sugars and sugar analogs mentioned in the previous paragraph, as well as oligonucleotide analogs based on non-ionic backbones, such as "peptide nucleic acids".
Another purpose of the instant invention is to provide nucleoside analogs in protected form that are suitable as precursors for the non-enzymatic synthesis of the non-standard oligonucleotide analogs.
Another purpose of the instant invention is to provide various phosphorylated derivatives of the stated nucleoside analogs, including triphosphates, which have utility in various enzymatic processes for the synthesis of the oligonucleotide analogs stated above.
Another purpose of the instant invention is to provide derivatives of the nucleoside analogs stated above that are degradation products of the oligonucleotide analogs stated above, and therefore help (for example) analyze these.
Another purpose of the instant invention is to provide 2′,3′-dideoxy analogs of the nucleoside analogs mentioned above, 3′-ONH2 derivatives, and other analogs and derivatives useful for the purpose of sequencing the oligonucleotide analogs mentioned above.
Another purpose of the instant invention is to provide compositions of matter wherein the oligonucleotide analogs mentioned above are attached to a solid phase, including a bead or microsphere, a two dimensional surface as part of a two dimensional array, and in a one dimensional array.
Another purpose of the instant invention is to provide processes for synthesizing said oligonucleotide analogs, both through template-directed polymerization and non-template-directed polymerization.
Another purpose of the instant invention is to provide processes for utilizing the compositions of matter described above. These include a variety of architectures that exploit a process that binds the stated oligonucleotide analogs to complementary oligonucleotide analogs containing one or more nucleobases that implements the complementary non-standard hydrogen bonding pattern, following an expanded set of Watson-Crick rules involving 6, 8, 10, and 12 letter DNA/RNA alphabets. These architectures include (without limitation) the stated oligonucleotide analogs as parts of compositions of matter that are beacons, nanostructures, dendrimers, and branched DNA molecules, and attached to solid supports such as beads, one dimensional arrays, two dimensional arrays, polonies, standard gels, and thermoresponsive gels, or in solution.
Another purpose of the instant invention is to provide oligonucleotide analogs as mentioned above for use in various architectures for detecting and sequencing oligonucleotides and oligonucleotide analogs, including within molecular beacons, in one and two dimensional arrays, on beads, in dendrimers that include both branched DNA and dendrimeric structures incorporating non-nucleosidic branching units, in assays involving cleavage reactions, in taggants and taggant detection schemes, and in nanostructures.
Another purpose of the instant invention is to provide the processes for utilization of the above described oligonucleotide analogs in the architectures above.
Another purpose of the instant invention is to provide functionalized derivatives of the nucleoside analogs mentioned above, carrying appendages that are fluorescent or that quench fluorescence, that assist in immobilization, that provide metal coordination sites, and that catalyze reactions, inter alia, when incorporated into the oligonucleotide analogs mentioned above, and into the processes mentioned above.
Another purpose of the instant invention is to provide processes for the repeated copying of the stated oligonucleotide analogs using template-directed polymerization, and copying of the copies in a polymerase chain reaction, having utility in oligonucleotide analog amplification, detection, and in vitro evolution to generate aptamers and oligonucleotide catalysts.
Another purpose of the instant invention is to provide non-standard nucleobases that are easily incorporated by DNA polymerases, RNA polymerases, and reverse transcriptases into the products of template-driven oligonucleotide synthesis. Various analyses of the interaction between polymerases and their substrates suggest that the polymerase seeks two unshared pairs of electrons in the minor groove, at position 3 of the purine (or analog) and at position 2 of the pyrimidine (or analog) [Steitz, T. in Burnett, R. M. and Vogel, H. J. (eds.) Biological Organization: Macromolecular Interactions at High Resolution; Academic Press: New York, 1987, pp. 45-55]. In addition, the base pairs that form three hydrogen bonds are expected to contribute more to duplex stability than pairs joined by just two hydrogen bonds.
These conditions are fulfilled for the compounds disclosed herein for implementing the pyDDA:puAAD hydrogen bonding pattern.

Non-standard nucleoside analogs with reduced epimerization


In marker edition mode, characters such as a character line is read in a closed area on a document marked with a marker. Then, the image data is analyzed to decide image processing means for marker edition such as coloring. A rectangular area including the image is recognized as image processing area. Even if the image is included partially in the closed area marked with a marker, a rectangular area including the image wholly can be specified as image processing area.

1. Field of the Invention
The present invention relates to an image processor, or in particular to an image processor having marker edition mode.
2. Description of the Prior Art
Various types of image processors have been proposed for so-called marker edition. In marker edition mode, an operator marks an area in a document with a marker, and the area is subjected to a predetermined image processing such as coloring. For example, an image processor disclosed in Japanese Patent laid open Publication No. 7-131628/1995 recognizes an area in a document enclosed with a marker as an image processing area. An apparatus disclosed in Japanese Patent laid open Publication No. 4-97262/1992 determines a rectangle which inscribes or circumscribes an area enclosed with a marker and recognizes the rectangle as an image processing area.
Image processing on an image in the image processing area is, for example, coloring, trimming or erasing. Further, in an apparatus disclosed in Japanese Patent laid open Publication No. 4-80885/1992, characters in the image processing area are recognized, and they are translated.
However, in prior art image processors, it is troublesome for an operator to specify with a marker an image processing area which includes a desired image in a document, especially an area including a particular character or characters. For example, in the apparatus described in Japanese Patent laid open Publication No. 4-46462/1992, when an operator marks a desired area to specify a rectangular area including a character line "ABC" correctly in a document shown in FIG. 1A, it is necessary to enclose entire characters of "A", "B", "C". If the entire characters are not enclosed with a marker, as shown in FIG. 1B, a rectangular area circumscribing a closed area marked with the marker includes a part of the character line "ABC", as shown in FIG. 1C. If trimming is performed on the image in the rectangular image, only the partial image of the character line "ABC" is reproduced when an image of the document is reproduced on a paper, as shown in FIG. 1D. In the apparatus described in Japanese Patent laid open Publication No. 4-97262/1992, an operator is also required to specify an enclosed area with a marker correctly and carefully.

Image processor with marker edition mode


A device includes a container for accommodating a medicament, a pressure route and a valve. The pressure route, disposed in the container, includes an extending pathway, a pressure-route inlet connected with a connecting port, and a pressure-route outlet extending toward a container bottom. The valve includes a first through hole connecting spatially the pressure-route inlet and outlet, and a valve body dividing the extending pathway into a pressure-in pathway and a pressure-out pathway. The device can convey the medicament such as a hemostatic agent more stably and smoothly to effectively avoid blocking upon a field of vision of an endoscope by the disturbed medicament while hitting a target tissue. Thereupon, the medicament can be provided more precisely, continuity of an endoscopic surgery can be improved, efficiency of hemostasis can be enhanced, and also surgery time can be substantially shortened.

Currently, no matter what kind of hemostatic treatments is applied to a body bleeding caused either by a wound or by a surgery, a step of depression to hemostasis is always necessary. In the art, medical accessories for hemostasis include band aids for external trauma, hemostatic sponges, hemostatic micro spheres, medical hemostatic membranes, hemostatic yarns made by non-woven technology, and so on. Though efficiency of hemostatic treatments can be increased by applying these accessories, yet a depression step for a period of time before the wound can be applied further treatments is required. After this depression period, it should be confirmed if any bleeding at the would is still there. In the case that the bleeding is still true, a hemostatic agent may be applied to the wound, and then the depression step shall be resumed till a hemostatic state is achieved. Such a hemostatic operation is obviously tedious and human-dependent. To a hemostatic treatment upon a bleeding wound at an internal organ or duct, the aforesaid hemostatic operation is usually hard to be performed accurately. In other words, to this type of wounds, a satisfied hemostatic treatment is barely to be obtained. Generally, if bleeding of a wound can be stopped only through a long-term local depression, a future healing of this wound would be an issue to be concerned. By having the bleeding in nasal sinus or nasal cavity as an example, an expanded hemostatic sponge is usually used for hemostasis, but it is easy to see that a complete hemostatic operation is hard to achieved. Generally, a 24-hour depression for the hemostatic sponge to stay in the nasal sinus or nasal cavity shall be needed, before the hemostatic sponge can be removed. Sometimes, the patients with this hemostatic treatment may meet nasal swelling, respiratory tract obstruction, and hemostatic difficulty in a following surgery. To those weak patients, an additional 24-hour observation and a possible secondary hemostatic treatment might be necessary, and thus work load upon related medical staff would be increased.
Though introduction of a hemostatic gel may improve bleeding at the wound, yet it might be less helpful in treating a major bleeding wound in a shorter time. It is obvious that the application of the hemostatic gel has a shortcoming in timing hemostasis.
In the marketplace, a spraying product can be applied to transfer the medicament onto the wound. Such a spraying product for evenly distributing the medicament powder is actually a powder-spraying means, not a direct hemostasis device. For example, though the well-known Yun-Nan white medicinal powder spray mainly for muscle sprains can be used to treat bruises and cuts, yet, according to the instructions, some other hemostatic medicament or direct depression shall be still applied for promoting the hemostasis.
In China utility patent No. ZL201420372934.3, a hemostasis device for wound and an assembly thereof are disclosed to include a container for holding a hemostatic medicament, a valve connected with a foreign pressure source and used for controlling open/close of the container, an application tube having one bent end, and a Tee connector connecting spatially the container, the valve and the application tube. The device can perform rapid hemostasis upon a bleeding tissue. However, since a pressure overshoot exists at the moment of opening the valve to escalate the injection pressure for driving the medicament powder, the initial injection of the hemostatic medicament powder would impact the tissue, and part of the powder would be bounced back possibly to block the field of vision upon the wound. Thereupon, continuous observation would be unfeasible. By have a laparoscopic surgery for example, the bounced-back hemostatic medicament powder would contaminate the laparoscope, and thus a clear observation for the surgery would be impossible. In other words, with this device, hemostasis effect and real-time observation of the surgery would be adversely affected, and thus the success rate and persistence of the endoscopic surgery would be reduced.

Medicament delivery device, apparatus and assembly


To provide a motorcycle front body structure of a simplified design, which contributes to reduction in motorcycle height and air resistance, by the employment of a dedicated removable cover for selectively opening and closing the access opening defined in an undersurface of the lamp unit, the motorcycle front body structure includes a fairing (21) having a lamp opening (21a), a lamp unit (23) positioned in the lamp opening (21a) and having an undersurface formed with an access opening (23c), and a cover (24) removably fitted to the lamp unit (23) for covering the access opening (23c). The lamp unit (23) and the cover (24) have respective undersurfaces exposed to an air flow passage (40) above a front wheel (3).

1. Field of the Invention
The present invention generally relates to a motorcycle front body structure and, more particularly, to the motorcycle front body structure, in which a lamp unit is positioned at a relatively low level so that the height of the motorcycle can be reduced.
2. Description of the Prior Art
In the conventional motorcycle front body structure including a fairing or cowling, the lamp unit accommodating headlights and position lamps is positioned inside the lamp opening defined in a front surface portion of the fairing, with a lower center portion of the lamp unit completely covered by a bottom wall of the fairing. In order to facilitate the replacement of the position lamps in the lamp unit, it is known to provide an access opening in the bottom wall of the fairing, which is closed by a removable lid or cover and which when the cover is removed, an access to the position lamps in the lamp unit can be available. See, for example, the Japanese Patent No. 3465436.
It has, however, been found that with the conventional motorcycle front body structure discussed above, the lamp unit cannot be positioned at a sufficiently lower position in view of the presence of the bottom wall of the fairing beneath the lamp unit and, as a result, it has been difficult to reduce the motorcycle height and, also, the air resistance acting on the motorcycle. In particular, where the access opening is employed in combination with the lid such as disclosed in the above mentioned patent, a space or gap between the lamp unit and the bottom wall of the fairing must be increased, resulting in a difficulty in reducing the motorcycle height.


The present document provides a scene recognition method and device based on ambient sound and a mobile terminal. The device includes: a sound collection module, a preprocessing module, a feature extraction module, a scene recognition module and a database. The method includes: collecting a sound signal; processing the sound signal into a frequency domain signal; extracting sound feature information from the frequency domain signal; inputting the sound feature information under a preset model, matching a model output result with weight values of sound sample models of scenes, and determining a scene corresponding to the sound feature information. The present document implements locating based on background sound information as the feature of the scene, so that the mobile terminal quickly and correctly recognizes the current scene under the maintaining low-consumption state.

Sound recognition technology is widely used in communication systems, for example, applying the sound recognition detection technology in a mobile communication system can improve the traffic processing capacity of the system. In addition, the sound recognition technology is increasingly used in a voice recognition filed, and the technology is already very mature, such as, IBM voice recognition input system ViaVoice, Microsoft voice recognition system SpeechSDK, etc.
With more and more smart phones are used in daily life, voice recognition is also well applied in the smart phones, e.g., iphone has issued a voice recognition application "Google Mobile App". Another improvement of that voice search is that accents can be selected, and Google can successfully recognize voices from different regions.
Due to the popularity of smart phones, a locating technology is also a hot spot for the application of the smart phone. At present, a scene recognition problem can be solved by making use of antenna-based locating technologies (e.g., WIFI, GSM and GPS) on which study has been widely made. With regard to outdoor locating, GPS has provided very ideal recognition accuracy. However, with regard to indoor locating, there is no ideal and thorough locating solution currently. With the restriction from factors such as internal topology and intense electromagnetic interference inside the building, the antenna signal strength often tends to vary irregularly, thereby making sensing devices unable to perform reasonable location speculation. It is found in study that WIFI signals fluctuate greatly during different periods over a day, and the variations of its strength are not even, and moreover we cannot ensure that the WIFI signals exist in all environments. On the other hand, signals of a base station are more stable at different time periods. However, since the deployment of base stations is not dense enough, there are a lot of difficulties in locating. In addition, such a locating method generally has a high requirement on perfection of infrastructure. However, such costs are undoubtedly high for developing regions. Locating based on GPS, GSM, WIFI signals cannot work in the indoor environment, or has larger locating error, and thus cannot distinguish indoor places geographically close to each other.

Scene recognition method, device and mobile terminal based on ambient sound


A rotary press with a stand, a rotor rotatably mounted around a vertical axis in the stand and being driven, which has an upper and a lower compression punch accommodation for upper and lower punches which co-operate with bores of a die plate of the rotor, and upper and lower control cam elements which can be detachably fastened on a cam carrier of the stand and which guide heads of the compression punches by means of control cams during the rotation of the rotor, characterized in that at least one control cam element, guiding the compression punch heads radially outside or radially inside, can be detachably fastened on the carrier and can be moved radially away from the punch heads when the fastening means is detached, so far that by-passing the punch heads, it can be taken out parallel to the axis of the rotor, towards the upside or towards the bottom side, respectively.

The present invention is related to a rotary press.
In a rotary press, a rotor is rotatably mounted around an upright standing axis in a stand and driven. The rotor body, mostly made up of one piece, contains an upper and a lower punch accommodation for upper and lower punches, which are guided axis parallel in bores. The compression punches co-operate with bores of a die plate, which is either formed in one part with the rotor body or represents a separate part. From DE 10 2004 040 163, the entire contents of which is incorporated herein by reference, it has also become known to compose the die plate from individual segments.
During the rotation of the rotor, the compression punches are moved axially. A great part of the movements is effected by control cams. For this purpose, control cam elements are attached on cam holders in the stand, which co-operate with the upper side and/or the bottom side of the head of the compression punches. Only in the region of compression stations with upper and lower compression roller, the compression punches are not guided by control cams.
For reasons of wear or a change of the specification, it is necessary to dismount the control cam elements and to replace them by other ones. For this purpose, it is necessary in the state of the art to remove machine shell parts and the filling device from the press stand, and to dismount plural punches or the die bore with the compression punches. In addition, powder existing in the machine must be sucked off. The mounting expenditure is therefore considerable. In addition, the operation of the rotary press is interrupted during the mounting time, of course. Thus, the exchange of control cam elements leads to a considerable interruption of the production time.
The present invention is based on the objective to provide a rotary press in which control cam elements can be dismounted without having to remove the compression punches before.


The prevention of corrosion on the surfaces of airwasher systems and particularly systems containing low levels of hardness is controlled utilizing a corrosion inhibiting amount of a composition including an alkali metal silicate, a hydroxycarboxylic acid or its water soluble salts, a polyacrylate or its water soluble salts, and a water soluble polymer which acts as a dispersant. Superior corrosion inhibition is achieved using the compositions of this invention as corrosion inhibitors, particularly in industrial airwasher systems employing mild steel metallurgy.

Airwasher systems, predominantly found in textile, electronics, pharmaceutical, and tobacco industries, provide humidity and temperature control in such plants. During the winter, airwasher systems increase the humidity in circulated air and during the summer, airwasher systems dehumidify recycled air. The removal of dust, odors, and particulates from the circulated air is another important function of air filtration and airwasher systems.
The most common design of an airwasher system is the vertical airwasher. Another system design still being used is the horizontal airwasher. Regardless of the design, airwasher systems have common features such as the basin, spray header trees and nozzles, and eliminator blades.
While a variety of problems can occur in the operation of airwasher systems, the most serious are poor corrosion control, where corrosion products can clog the spray headers, resulting in decreased airwasher efficiency. Other factors that can lead to spray nozzle plugging, specifically in the textile industry, include contaminants such as lint, cotton fibers and sizing agents such as polyvinyl alcohol, starches, waxes, and the like. An additional problem in such systems is the fouling of the equipment caused by microbiological activity.
Water soluble polymers such as polyacrylic acid have been utilized as additives to disperse solids contained in industrial cooling water systems and as an aid to prevent the adherence of scale on the metallic surfaces of such systems in contact with water. Likewise, biocides have been added to control the formation of microbiological growth in industrial systems. The presence of microbiological growth can provide a location where corrosion can occur, underneath the deposit and where water flow is minimal and untreated.
However, due to the pending environmental regulations and restrictions, a non-metal, non-phosphorus corrosion inhibiting program is needed for use in the industries that typically employ airwasher systems.
Shim et al., U.S. Pat. No. 5,589,106 discloses compositions for preventing corrosion of metallic surfaces in contact with industrial cooling water comprising: a hydrocarboxylic acid or its water soluble salts, a water-soluble alkali metal silicate, a water-soluble dispersant polymer, and optionally other corrosion inhibitors and biocides. Persinski et al., U.S. Pat. No. 4,640,793 discloses synergistic compositions which act as scale and corrosion inhibitors comprising two water-soluble polymers.
Neither Shim et al. nor Persinski et al. describes a composition for the treatment of air washer systems as described by this invention. There are several differences between cooling water systems and air washer systems, notably their uses. The main purpose of a cooling water surface is to remove heat from a surface, typically a heat exchanger, and then reject that heat to the environment, while the main purpose of an air washer is to condition the environment of the workspace. This would include both temperature and humidity control. The water of an air washer system is used to reject heat to an air conditioning machine, which is the opposite of what occurs in a cooling water system.
Another difference between the two types of systems concerns their respective methods of operation. Air washers operate in two distinct modes depending upon the season of operation. Typically during the winter, the water will evaporate and concentrate similar to a cooling water system. This occurs to increase the humidity in the work space. In the summer (higher humidity season), the water will `deconcentrate` as water is pulled from the atmosphere to reduce the humidity of the work space. The variability of water chemistry conditions that occurs due to seasonal variations is in contrast to cooling water systems that evaporate water to reject heat and are consistently at a higher cycle of concentration.
Furthermore, air washer systems are designed to scrub/clean material from the work space atmosphere, while cooling towers are designed to remove heat from a process. During this process, inadvertent contamination from the airborne contaminants occurs. Because of this design, any air washer treatments must be able to control a larger amount of airborne contaminants. For example, textile air washers will contain natural or synthetic fiber contaminants, tobacco air washers will contain tobacco dust, and electronics air washers will contain organic solvents which must be removed. Such contaminants are typically not found in cooling water systems.
The main treatment for cooling water systems is geared towards corrosion/fouling control on a heat transfer system. This is in contrast to air washer treatments being geared towards dispersancy of airborne contaminants and corrosion control of non-heat transfer surfaces. As described above, there are numerous differences between the two types of systems. In industrial water treatment, each system has a unique set of problems which can be overcome by the selection of an appropriate treatment. Since the two systems are different, a treatment suitable for one system would not also necessarily be suitable for the other. (For example, one would not use a boiler treatment program in a cooling tower where they may both be considered industrial water applications.)
Bush, U.S. Pat. No. 4,279,768 discloses a composition for removing scale built up on metallic working surfaces utilizing a synergistic blend of a chelant, polymeric conditioners, a gluconate, a triazole and sodium sulfite. Mullins, U.S. Pat. No. 4,961,878 discloses a composition of inhibiting metal corrosion in a closed aqueous cooling system which may include acrylate polymer, tolyltriazole, amine oxide and silicate.
However, neither the '878 compositions nor the '768 compositions are useful for addressing the specific problems associated with air washer systems solved by the invention described herein. The inherent differences between the two systems as described above indicate that it is not necessarily true that effective treatments for cooling water systems would be equally effective in air washer systems.
It is accordingly an object of this invention to provide to the art a novel, non-metal, non-phosphorus, high performance chemical corrosion inhibition treatment program which can be used in airwasher systems to help prevent the corrosion of the metal surfaces in contact with the water contained in such system. The corrosion inhibitors of this invention have been found to be particularly effective in preventing corrosion from occurring on the iron, mild steel, yellow metals, and galvanized steel surfaces of airwasher systems in contact with industrial cooling water.

Non-Phosphorus corrosion inhibitor program for air washer system


Disclosed is a burner register assembly having an air register assembly for imparting a controlled vortex swirl to secondary combustion air of a furnace in order to entrain the fuel and primary air of the furnace and carry them into the furnace interior. The assembly may comprise a series of arcuate vanes circumferentially spaced about the fuel and primary air nozzle, the vanes being designed to induce both turbulence and a well defined vortex to the secondary air flow. A separate air valve, such as a butterfly valve, is provided upstream of the air register assembly to regulate the volume of secondary air flow. Shadow vanes may also be provided in the vicinity of the air register assembly outlet, and positioned adjacent the furnace walls in order to protect the air register assembly from furnace heat, particularly when the burner associated with the air register assembly is idle and the secondary air flow is lowered.

The present invention is primarily directed to coal fired furnaces although it will be understood by the artisan that a similar system can also be used on oil fired furnaces, hybrid coal/oil furnaces, gas fired furnaces and furnaces which burn other materials. It should therefore be understood that while the description which follows is directed to pulverized coal burning furnaces, that is by way of example only and not a limitation. The present invention is generally applicable in any furnace requiring excess air to assure complete combustion or furnaces requiring excess air as load is reduced.
Typical prior art burner arrangements for a furnace comprises a burner or coal nozzle through which pulverized coal and primary air are introduced into the furnace. The primary air typically supplies only about 20 percent of the air needed to fully oxidize the fuel. Therefore, each burner nozzle is provided with a secondary air supply. The secondary air supply typically consists of a "windbox" or air plenum that is in communication with a burner register. The prior art burner registers are of two general types. The first type utilizes pivoting slat vanes journaled between two ring members to form a band The coal nozzle is centrally located along the axis of the band. The vanes pivot from a fully closed position, where the end of one slat coincides with the beginning of the next thus forming a closed ring about the fuel nozzle, to an open position where the vanes are positioned generally radially with respect to the fuel nozzle, thus permitting the free flow of secondary air. Such a register utilizes a single assembly to perform the dual functions of controlling both the volume and direction of the secondary air supply. An example of such a register is taught in Chapter 9 of "Steam/Its Generation and Use" by the Babcock and Wilcox Company, 1978 Edition.
The second type of prior art secondary air register is formed from a plurality of movable, radial "pie" shaped wedges which in the closed position form a closed circular valve surface and which, as opened, operates to control the volume and direction of secondary air introduced from an associated windbox into the furnace along with the fuel and primary air. These prior art arrangements suffer from various deficiencies (discussed below) which the present invention has overcome.
Owing to their considerable number of required interrelated moving parts, which were subjected to the severe environmental conditions existing in the space adjacent to the furnace, the prior art registers were unreliable and subject to frequent and costly repair efforts. These repairs would require the shutting down of the furnace facility at considerable expense and inconvenience to the operator of the furnace (usually an electrical generation utility).
In addition, the prior art registers introduced secondary air into the furnace in a turbulent but generally random pattern with only a small and ineffective swirl component. This led to the incomplete combustion of the fuel and to erosion of the furnace walls in the vicinity of the burner due to the action of deposits of only partially burned fuel along the furnace walls. Moreover, the prior art registers required the introduction of large amounts of secondary air even when the burner was idle in order to protect the register from heat damage. This required that the furnace be equipped with the capacity to generate and otherwise process large amounts of secondary air and led to the problem of erosion or wear damage occurring in the various furnace components exposed to the higher velocity air flow (e.g., fans, registers, heat exchangers, superheaters, etc. It is noted that the wear resulting from the gas flow against the elements in the flow path is a function of the cube of the gas velocity.
The operation of prior art registers resulted in inefficient furnace operation, especially at low loads. Moreover, due to the lack of a well defined fuel/air flow pattern, there was a tendency in prior art furnaces for the intense heat and pressure variations existing in the furnace to cause the fuel from the nozzle to be "blown" against the relatively cold furnace walls. This resulted in poor combustion of the coal and additional damage to the furnace walls.


The invention relates to an electrodeless device for administering an electrocardiogram consisting essentially of a single flexible sheet having multiple electrical strips or wires pre-positioned for placement on a patient's chest. The device includes at least two positioning means.

Electrocardiographic monitoring and telemetry have been in use in the United States for some time for screening and diagnosis of cardiopathy. Electrocardiography provides a graphic registration, commonly known as an EKG, of movements of the heart using electrical signal sensing. In general, electrical leads used to transmit signals from the patient's cardiovascular system are fixed to the skin of the patient individually, at suitable locations, using suction cups and conductive adhesives to provide the necessary electrical connection for reading the heart movements through a patient's skin.
For screening and evaluation, the patient should be ambulatory so that readings can be taken during different degrees of physical exertion to demonstrate the reaction of the heart to differing stresses. A standard type of testing includes electrocardiographic monitoring of a patient during a set of standardized treadmill exercises. It is well recognized that this type of screening and evaluation are important for diagnosis of new ischemic cardiac episodes in the chronically symptomatic cardiac patient as well as the identification of "silent ischemic" periods of myocardial oxygen insufficiency not associated with classic chest pain. These ischemic electrocardiographic changes can be accurately recognized only if a full screen electrocardiogram is performed. The standard full screen electrocardiogram includes readings taken by electrically conductive leads at standard chest positions combined to provide readings.
Periodic electrocardiograms can provide a physician with a cardiographic profile of an individual patient for early detection and diagnosis of cardiovascular diseases. For purposes of providing an accurate profile, it is important that each electrocardiogram be taken with leads affixed about the same location on the patient. The accuracy of each electrocardiogram requires that the leads be accurately placed and that they remain fixed while the patient is ambulatory. In addition, to provide accurate information for an individual patient, a series of electrocardiograms are taken and compared to one another to detect changes in the reaction of the individual patient's heart to the same stresses. Therefore, it is important that placement of the leads be consistent from one electrocardiogram session to another.
As can be appreciated, accurately placing and securing a large number of leads can be difficult and time consuming. In addition, electrocardiograms are taken periodically and the results compared to one another to provide a continuing profile of an individual patient's heart movements for early diagnosis and treatment of heart disease and to identify "silent ischemic" periods of myocardial oxygen insufficiency in chronically symptomatic cardiac patients. It would therefore be advantageous to have a device for accurate placement of leads for accurately reproducing test conditions for comparison between testing episodes.
Although a full screen, twelve point electrocardiogram provides the most accurate picture for recognizing ischemic electrocardiographic changes, because of the time required to place and secure individual leads, electrocardiograms taken during an acute symptomatic episode of a cardiac patient are generally limited to two- to four-lead readings. It would therefore be advantageous to have a device which enables more leads to be accurately placed and secured quickly during an acute symptomatic episode.
U.S. Pat. No. 4,608,987 to H. E. Mills relates to a vest-like garment having a plurality of aperatures adapted for receiving electrodes. However, there is no provision to ensure that the electrodes are placed each time of reuse of the vest about the same location.
U.S. Pat. No. 4,583,549 to S. Manoli relates to an ECG electrode pad with a plurality of ECG electrodes which are repositioned with regard to each other and not with reference to their previous position.
U.S. Pat. No. 4,365,634 to Bare et al discloses a multi-terminal electrode construction having a pair of separate support members adapted for the transcutaneous application of an electrode to a patient. A multiterminal design is provided by a conductive pattern printed on a semiflexible sheet. The pattern is printed with conductive ink in a binder composition. However, there is no means provided which can ensure the reapplication of the terminals to the same location so as to obtain a better comparison of test results.
U.S. Pat. No. 4,593,698 to R. J. Athans discloses an electrocardiograph sensor positioning device for repeatedly positioning electrocardiograph sensors. The device establishes a longitudinal reference between two anatomical landmarks on an individual. A second reference path is then found and recorded. The recorded locations are necessary to ensure a similar location. One of the problems with the use of the device requires that the second examining physician have the information from the first physician in order to obtain readings at the same locations. The device of the invention provides uniform examination without requiring information from others on placement of the electrodes.
U.S Pat. No. 4,763,660 discloses a multilayer disposable electrode belt device which contains a plurality of flexible non-conductive layers. There is also provided anatomatical placement reference means.
A vest provided with prearranged electrodes is shown in FIG. 4.
Telephonic units for transmitting ECG signals to ECG receiving equipment at a cardiologist's office are described generally in U.S. Pat. No. 3,910,260. Usually such transmission takes place in emergency vehicles where prior medical history may not be readily available. In order to obtain meaningful and reliable information repeatable ECG signals are necessary for the cardiologist. None of the prior art devices have provided a low cost solution to obtaining repeatable ECG signals in the field by untrained or non-professionals parties.
The present invention provides an easily manufactured accurate, repeatable placement of leads for electrocardiograms which is repeatable without knowledge of the previous locations. The device of this invention lowers the time involved in placement and affixation by providing a sensor sheet incorporating multiple leads which are preferably pre-wired to a terminus that can connect to a standard electrocardiographic cable or to a telemetric unit, as more fully discussed below.


A low voltage analog front end (AFE) includes a differential transistor pair which converts an input voltage, typically A.C.-coupled to the pair's control inputs, to a differential current. Impedance networks connected to each transistor's control input are joined together at a common node, and a current source is connected to the node which causes DC bias currents to be mirrored through the pair's current circuits, so that the AFE's differential output current comprises a differential current produced by the pair in response to an input voltage and superimposed on the DC bias currents. The current source preferably generates mirrored currents which are larger than its reference current to linearize the pair's response and to provide the AFE with a wide dynamic range. An input to the AFE sees a low impedance which is about equal to the sum of the impedance networks, which can be resistive or complex as needed. The AFE has widespread application as a front end circuit, serving as a low voltage input stage for a Gilbert mixer, for example. By generating bias currents via the pair's control inputs, supply voltage headroom requirements are reduced, improving a system's dynamic range and/or enabling the use of lower voltage power supplies. The AFE can be configured as either a differential or single-ended voltage-to-differential current converter.

1. Field of the Invention
This invention relates to the field of analog front end circuits, particularly those used to convert an input voltage to a differential current.
2. Description of the Related Art
Circuits that convert an input voltage to a differential current are widely used, especially within RF circuit blocks; these V-to-I conversion circuits are referred to as "analog front end" (AFE) circuits. They are typically implemented using a differential pair of npn transistors which are emitter-coupled, and are biased with a current source connected to the coupled emitter junction; the input stage of a Gilbert mixer is an example.
A known AFE circuit is shown in FIG. 1. The emitters of a differential pair of npn transistors Q1 and Q2 are coupled together at a node 8, and the pair is biased with a current source consisting of an npn transistor Q3, with Q3's collector connected to the node 8, its emitter connected to ground through an emitter resistor R.sub.e, and its base connected a bias voltage V.sub.b. A differential input voltage composed of signals RF+ and RF- is connected across the respective bases of Q1 and Q2, and differential current signals I.sub.out+ and I.sub.out- are produced at their respective collectors. An input resistor R.sub.i is often connected across the differential input voltage lines to provide a particular input impedance to the incoming signal; for example, 50 .OMEGA. is typically presented to an RF input. The differential output current is sometimes converted back to a differential voltage by connecting the collectors of Q1 and Q2 to a supply voltage V.sub.supply via load resistors R.sub.L1 and R.sub.L2, to produce differential output voltage signals V.sub.out+ and V.sub.out-. AFE's of this type are discussed, for example, in Gray and Meyer, Analysis and Design of Analog Integrated Circuits, John Wiley and Sons, Inc. (1984), pp. 194-197.
A problem with the circuit of FIG. 1 is that some of its supply voltage headroom is lost to the current source connected to the coupled-emitter junction. "Headroom" is defined as the portion of a circuit's supply voltage which is available for use by the circuit's signals. Depending on the circuit's design requirements and temperature, the voltage at Q3's emitter V.sub.e is typically between about 200 and 500 mv. Q3's base-emitter voltage V.sub.be is typically between about 700 to 900 mv (for a npn transistor), and its collector-base voltage V.sub.cb is about 0 to 300 mv. Adding these voltages together produces a voltage at node 8 of between about 0.9 and 1.7 volts. Additional voltage is necessarily dropped across Q1 and Q2. If the voltage at node 8 is one volt, and another one volt is dropped across Q1 and Q2, V.sub.out+ and V.sub.out- can only assume voltages between V.sub.supply and 2 volts. This loss of valuable supply voltage headroom can be a significant portion of the total supply voltage, which is often as low as 3 volts. Lost headroom reduces the dynamic range of the AFE and can necessitate the use of a higher voltage power supply, which increases the power dissipation needs of the circuitry using the AFE and subsequently increases the weight of the system employing the circuit.


A conveyor apparatus having a conveyor chain and at least one supporting arm used for attaching thereto objects which are to be conveyed. The supporting arm has one of its ends connected to the conveyor chain via an overload protection means. The overload protection means has a tilting joint which is provided between the supporting arm and the conveyor chain and permitting reversible tilting of the supporting arm relative to the conveyor chain in response to a predetermined load. In the structural design of the conveyor apparatus the tilting joint is acted upon by a helical tension spring.

The present invention relates to a conveyor apparatus of the type having a chain and a tiltable pin. Such a conveyor with a conveyor chain and a tiltable pin is known from U.S. Pat. No. 4,533,039. The pin comprises a base secured to the chain. The sleevelike main body of the pin is connected to the base via a piece of wire rope. In order to permit tilting of the pin, the fastening point of the piece of wire rope is arranged in the interior of the main body such that it is adapted to be displaced against the tensioning force of a compression spring resting on the displaceable fastening point and on a plug which is secured to the main body and through which the piece of wire rope extends. This structural design is comparatively complicated and, consequently, expensive.
A further conveyor apparatus is shown in German Utility Model 93 14 261. This conveyor apparatus is used for transporting cans or other hollow articles. The cans are attached individually to respective supporting arms, which extend horizontally and transversely to the direction of transport and which have one of their ends secured to the conveyor chain. The other end of the respective supporting arm, or rod, is free and extends freely away from the conveyor chain over a length corresponding at least to the length of the can. This structural design inevitably has the effect that, especially at higher speeds of the conveyor chain, the supporting arm will begin to vibrate. Due to the comparatively long lever arm defined by the supporting arm, there is the risk that the conveyor chain will be affected. In order to avoid this, the supporting arm is connected to the chain via a damping member which is capable of absorbing vibrations. In view of the fact that although the damping means is capable of absorbing the vibrations during normal operation, it is incapable of absorbing higher loads which act on the supporting arm and of keeping them away from the chain. The prior art conveyor apparatus is provided with an overload protection means in the form of a predetermined breaking point arranged on the supporting arm close to the point where the supporting arm is secured to the conveyor chain. This predetermined breaking point is provided for guaranteeing that the supporting arm will break without seriously affecting the conveyor chain when an excessively strong force acts on said supporting arm. When a predetermined breaking point is used, the predetermined load, which is to be avoided so as to prevent the conveyor chain from being damaged, must not be chosen too small such that the regular operation of the conveyor chain is not disturbed too often and too long. On the other hand, the predetermined force must not be so high as to prevent the overload protection means from accomplishing its task in a reliable manner, i.e., the task of protecting the conveyor chain against damage. The use of a predetermined breaking point makes it very difficult to control the predetermined load. It is difficult to eliminate by means of a predetermined breaking point loads which are, in principle, not high, but which recur frequently and cause then damage to the conveyor chain.
Hence, it is the object of the present invention to provide a conveyor apparatus with an overload protection means having a simplified structural design.

Deflectable chair mounted pin assembly for conveyor


Provided is a manufacturing method of a rare-earth magnet with high coercive force, including a first step of pressing-forming powder as a rare-earth magnet material to form a compact S, the powder including a RE-Fe—B main phase MP (RE: at least one type of Nd and Pr) and a RE-X alloy (X: metal element) grain boundary phase surrounding the main phase; and second step of bringing a modifier alloy M into contact with the compact S or a rare-earth magnet precursor C obtained by hot deformation processing of the compact S, followed by heat treatment to penetrant diffuse melt of the modifier alloy M into the compact S or the rare-earth magnet precursor C to manufacture the rare-earth magnet RM, the modifier alloy including a RE-Y (Y: metal element and not including a heavy rare-earth element) alloy having a eutectic or a RE-rich hyper-eutectic composition.

1. Field of the Invention
The present invention relates to a method for manufacturing a rare-earth magnet.
2. Background Art
Rare-earth magnets containing rare-earth elements such as lanthanoide are called permanent magnets, and are used for motors making up a hard disk and a MRI as well as for driving motors for hybrid vehicles, electric vehicles and the like.
Indexes for magnet performance of such rare-earth magnets include remanence (residual flux density) and a coercive force. Meanwhile, as the amount of heat generated at a motor increases because of the trend to more compact motors and higher current density, rare-earth magnets included in the motors also are required to have improved heat resistance, and one of important research challenges in the relating technical field is how to keep a coercive force of a magnet at high temperatures. For example, in the case of a Nd—Fe—B magnet as one of rare-earth magnets that is used often for vehicle driving motors, attempts are made to increase the coercive force of the magnet by developing finer crystal grains, using an alloy having a composition containing Nd more or adding heavy rare-earth elements such as Dy and Tb having a good coercivity performance, for example.
Among heavy rare-earth elements to improve the coercivity performance, Dy is used often for this purpose. However, the amount of deposits of Dy is limited, and Dy is an expensive material. Therefore it is one of important challenges in our country at the nation level to develop a Dy-less magnet to keep the coercivity performance while reducing the amount of Dy or a Dy-free magnet to ensure the coercivity performance without containing Dy at all.
The following briefly describes one example of the method for manufacturing a rare-earth magnet. For instance, Nd—Fe—B molten metal is solidified rapidly to be fine powder, while pressing-forming the fine powder to be a compact. Hot deformation processing is performed to this compact to give magnetic anisotropy thereto to prepare a rare-earth magnet precursor (orientational magnet), into which a modifier alloy is penetrant-diffused to improve the coercive force, thus manufacturing a rare-earth magnet.
Note that JP Patent Publication (Kokai) No. 2011-035001A (Patent Document 1) and JP Patent Publication (Kokai) No. 2010-114200 A (Patent Document 2) disclose a method for manufacturing a rare-earth magnet including a nano-crystalline magnet by adding high-coercivity heavy rare-earth elements by various methods.
The manufacturing method disclosed in Patent Document 1 is to evaporate an evaporation material containing at least one of Dy and Tb so as to be grain-boundary diffused into a hot-deformed compound from a surface thereof.
This manufacturing method requires high-temperature processing at about 850 to 1,050° C. during the evaporation of the evaporation material, and such a temperature range is specified to improve remanence and suppress quick growth of crystal grains.
The heat treatment in the range of as high as 850 to 1,050° C., however, causes grain coarsening, resulting in increase of risk for deterioration in coercive force. That is, even when Dy or Tb is grain-boundary diffused, the resultant may not show a sufficient high coercive force.
Patent Document 2 discloses a manufacturing method that brings at least one type of element of Dy, Tb and Ho or an alloy of the element and at least one type of element of Cu, Al, Ga, Ge, Sn, In, Si, P and Co into contact with the surface of a rare-earth magnet, and performs heat treatment for grain-boundary diffusion so that the grain size does not exceed 1
Patent Document 2 mentions that the temperature range of 500 to 800° C. for heat treatment leads to excellent balance between a diffusion effect of Dy or the like into crystal grain boundary phase and a coarsening suppression effect of crystal grains by the heat treatment, whereby a high coercivity rare-earth magnet can be easily manufactured. Patent Document 2 discloses various embodiments using a Dy—Cu alloy and performing heat treatment at 500 to 900° C. Among these embodiments, a typical 85Dy-15Cu alloy has the melting point of 1,100° C. Accordingly, in order to penetrant-diffuse the molten metal thereof, high-temperature treatment is required at 1,000° C. or higher, and as a result grain coarsening cannot be suppressed.
In view of these circumstances (rise in the price of Dy or the like, grain coarsening under a high-temperature atmosphere to diffuse a modifier alloy containing high-melting heavy rare-earth elements into grain boundary phase or the like), the present inventors have come up with the idea for a method using a modifier alloy (modifier phase) not including heavy rare-earth metals such as Dy and Tb and penetrant-diffusing melt of the modifier alloy under a relatively low-temperature condition, thus manufacturing a high coercivity rare-earth magnet, especially having a high coercive force under a high-temperature atmosphere.

Method for manufacturing rare-earth magnet


A technique is described for table grid detection and separation during the analysis and recognition of documents containing table contents. The technique includes the steps of table detection, grid separation, and table cell extraction. The technique is characterized by the steps of detecting the grid lines of a table using, for example, inverse cell detection, separating noise and touching text from the grid lines, and extracting the cell contents for OCR recognition.

Reading table content plays a very important role in parsing documents that contain table contents. Such documents can be invoices, bills, shipping receipts, medical or insurance claim forms, financial spread sheets, and the like. Considering the large variations of table designs on these documents, providing a correct reading order that helps the parsing of document content is a challenging task. Reading tables from document images, especially when the images have skewing or handwriting, is even more challenging. The technique described herein addresses these issues by providing a methodology for detecting and separating table grids from scanned document images.


The semiconductor oxide layer that forms a part of the spacer layer in the inventive giant magnetoresistive device (CPP-GMR device) is composed of zinc oxide of wurtzite structure that is doped with a dopant given by at least one metal element selected from the group consisting of Zn, Ge, V, and Cr in a content of 0.05 to 0.90 at %: there is the advantage obtained that ever higher MR ratios are achievable while holding back an increase in the area resistivity AR.

1. Field of the Invention
The present invention relates to a magnetoresistive device adapted to read the magnetic field intensity of magnetic recording media or the like as signals, and a thin-film magnetic head comprising that magnetoresistive device as well as a head gimbal assembly and a magnetic disk system, one each including that thin-film magnetic head.
2. Explanation of the Prior Art
In recent years, with an increase in the longitudinal recording density of magnetic disk systems, there have been growing demands for improvements in the performance of thin-film magnetic heads. For the thin-film magnetic head, a composite type thin-film magnetic head has been widely used, which has a structure wherein a reproducing head having a read-only magnetoresistive device (hereinafter often called the MR device for short) and a recording head having a write-only induction type magnetic device are stacked together.
The MR device, for instance, includes an AMR device making use of the anisotropic magnetoresistive effect, a GMR device harnessing the giant magnetoresistive effect, and a TMR device tapping the tunnel-type magnetoresistive effect.
The reproducing head must have some characteristics in general, and high sensitivity and high output in particular. For the reproducing head capable of meeting such demands, there has already been a GMR head mass produced that makes use of a spin valve type of GRM device.
Such a spin valve type GMR device generally comprises, as part of the device, a nonmagnetic layer, a first magnetic layer (the so-called free layer) formed on one surface of the nonmagnetic layer, a second magnetic layer (fixed magnetization layer) formed on another surface of the nonmagnetic layer, and a pinning layer (generally an antiferromagnetic layer) formed in contact with the fixed magnetization layer that faces away from the nonmagnetic layer. The free layer operates such that the direction of magnetization changes in response to a signal magnetic filed coming from outside, and the fixed magnetization layer has the direction of magnetization fixed by an exchange coupling magnetic field from the pinning layer (antiferromagnetic layer). With such device structure, MR changes are achievable via a difference in the relative angle of spins in two such ferromagnetic layers.
As head size diminishes, there is a mounting demand for an arrangement capable of increasing the MR ratio, and the so-called current narrowing type head has been proposed as one of the prior arts capable of obtaining large MR ratios while resistance is kept low (see JP(A)2005-243154 (JP Patent No. 3993175)). However, that head structure is not compatible with a demand for drastic decreases in the head area: much difficulty is encountered in achieving sufficient size reductions, with high precision, of a Cu-pillar located in a spacer and used for narrowing currents. For this reason, it is difficult to hold back characteristics variations for each device, and much is still desired for the reliability of the device itself, offering an obstacle to practical use.
JP(A)2003-8102 that is another prior art discloses a CPP-GMR device that comprises a fixed magnetization layer including a magnetic film having the direction of magnetization substantially fixed in one direction, a free magnetization layer including a magnetic film having the direction of magnetization changing in response to an external magnetic field, a nonmagnetic metal intermediate layer interposed between the fixed magnetization layer and the free magnetization layer, and a resistance adjustment layer interposed between the fixed magnetization layer and the free magnetization layer and formed of a material having up to 1022/cm3 of conduction carriers. According to this proposal, the problem with characteristics variations for each device is eased off because of no use of any Cu-pillar for the formation of the narrowing structure. In addition, adjustment of device resistance enables a proper area resistivity to be achieved. However, the effect on improvements in the MR ratio is limited because the MR ratio depends largely on the nature of the nonmagnetic metal intermediate layer.
To solve such a problem with JP(A)2003-8102, the inventors have already filed JP(A)2008-177272 to propose a CPP-GMR device wherein 1 to 8 at % of a given metal are contained in a semiconductor oxide layer forming a part of the spacer layer.
According to this proposal, the addition of the given metal in an amount of at least 1 at % has the features of maintaining ohomic conduction and reducing shot noises, and the proper area resistivity is achieved, too. However, there is no end to the demand for MR ratio improvements: much more improvements are still now in great demand.
The situations being like this, the present invention has been made for the purpose of providing a novel magnetoresistive device that is just only capable of overcoming the aforesaid problems with the prior art but also can make the MR ratio high while holding back an increase in the area resistivity, and a thin-film magnetic head comprising that magnetoresistive device as well as a head gimbal assembly and a magnetic disk system, one each comprising that thin-film magnetic head.

Magnetoresistive device of the CPP type, and magnetic disk system


A 3-dimensional image acquisition apparatus acquires images to be used for 3-dimensionally reconstructing an object by picking up the object by a camera twice or more in an image acquisition set including picking up at least once the object carrying a pattern projected onto it by a projection light source. The apparatus comprises a light projection information memory configured to store information on projection of light including information on the time for projecting light for the purpose of projecting the pattern in the image acquisition set, an image acquisition progress information memory configured to store information on the progress of image acquisition in the image acquisition set, and a controller configured to control the projection of light by the projection light source and the picking up by the camera on the basis of the stored information on projection of light and the stored information on the progress.

1. Field of the Invention
This invention relates to a 3-dimensional image acquisition apparatus for picking up an image of an object twice or more than twice including picking up at least once an image of the object that carries a pattern projected on it for the purpose of 3-dimensionally reconstructing the object, and also to a 3-dimensional image acquisition method. The present invention also relates to a 3-dimensional reconstruction system for 3-dimensionally reconstructing an object by carrying out such an image acquisition.
The present invention further relates to a light projection unit adapted to be connected to a camera that can continuously image an object and output timing signals for defining timings of imaging or projecting light for projecting a pattern and also to a light projection method to be used for such a light projection unit.
2. Description of the Related Art
U.S. Pat. No. 6,370,335 B1 discloses a flash unit for flashing light for a number of times at predetermined regular intervals for the purpose of 3-dimensional image acquisition. The disclosed flash unit can alternately flashlight with a pattern (projection flash) and without any pattern (lighting flash) by sequentially switching the externally input flashing signals.
U.S. Pat. No. 2002/0118,970 A1 describes a stereo-adaptor that enables a camera to acquire a parallax image when it is connected to the imaging optical system of the camera. The stereo adaptor is provided with a light emitting section for ligating a pattern projector for projecting a pattern onto an object or the object itself.

3-dimensional image acquisition apparatus and method, 3-dimensional reconstruction system, and light projection unit and light projection method therefrom