The present invention is in the field of nucleic acid binding compounds comprising 7-substituted 7-deaza-8aza-2,6-diamino-purine bases, compounds useful for the preparation of such compounds, various uses thereof and methods for the determination of nucleic acids using said compounds in the field of diagnostics.

Nucleic acids have been found to be useful analytes for the determination of the presence or absence of genes or microorganisms in human body fluids, food or environment in the field of health care. Nucleic acid analysis has found widespread use after the introduction of nucleic acid amplification, like the Polymerase Chain Reaction (PCR, see U.S. Pat. No. 4,683,202). Thus, sufficient amounts of nucleic acids are available from each sample. The nucleic acids can be determined from this pretreated sample using a variety of different techniques, dependent on the particular purpose. Most assays require the use of a probe which is either immobilized or immobilizable or is labelled by attachment of one or more reporter groups.
A reporter group has the characteristics to be itself capable to be determined or it can be reacted with reagents that make the probe determinable via said reporter group. Thus, for example, probes that are labelled by reporter groups can be determined, as can be hybrids that contain the probe and a nucleic acid to be determined. In case of immobilized probes, the hybrid between the probe and the nucleic acid to be determined is determined at the solid phase to which the probe is bound. In a particular form of assays, not only one nucleic acid having a specific sequence, but a large number of nucleic acids of different sequence is determined. For this purpose, the probes are immobilized in tiny spots in an array on a flat surface such as a glass chip (EP-A-0 476 014 and TIBTECH (1997), Vol. 15, 465-469, WO89/10977, WO89/11548, U.S. Pat. Nos. 5,202,231, 5,002,867, WO 93/17126). Further development has provided methods for making very large arrays of oligonucleotide probes in very small areas.(U.S. Pat. No. 5,143,854, WO 90/15070, WO 92/10092). Microfabricated arrays of large numbers of oligonucleotide probes, called "DNA chips" offer great promise for a wide variety of applications (see e.g. U.S. Pat. Nos. 6,156,501 and 6,022,963).
However, nucleic acid determinations often suffer from the problem that the base pairing possibilities between the natural bases A and T and C and G have different stability. This can be attributed to the different capability of these bases to form hydrogen bonding. Thus, the dA-dT-base pair has two hydrogen bridges, while the dG-dC-base pair has three hydrogen bridges. This results in different melting temperatures (Tm) of hybrids, depending on the GC content [1-3]. The higher the GC content, the higher the Tm. The hybridisation strength or the degree of hybridization may be investigated by the measurement of the Tm of the resulting duplex. This can be done by exposing a duplex in solution to gradually increasing temperature and monitoring the denaturation of the duplex, for example, by absorbance of ultraviolet light, which increases with the unstacking of base pairs that accompanies denaturation. The Tm is generally defined as the temperature midpoint of the transition from a fully duplex structure to complete denaturation, i.e. the formation of two isolated single strands.
Therefore in routine nucleic acid analysis, there is often the wish to change the Tm of a nucleic acid molecule. For example, for certain purposes it may be advantageous to equalize or harmonize the Tm of nucleic acids of the same length or to make it even independent from the length of the nucleic acid or the binding region in order to be in the position to apply similar hybridization conditions for all assays. This is particularly necessary for assays using arrays, as on such arrays the hybridizing conditions for each probe must be identical. One solution was the use of low hybridization temperatures. Under such conditions, many nucleic acids having a low degree of base sequence complementarity will bind to the probe. This is called unspecific binding which does not allow discrimination between similar sequences. Another proposal was directed to the use of chemical reagents in the hybridization mixture, for example the addition of tetramethylammonium chloride (TMAC). This reagent reduces the difference between the stability of dG-dC and dA-dT base pairs but the effect is insufficient for short oligonucleotides. Further the addition of salts such as TMAC may not be appreciated as it complicates the optimization of the assay. Another proposal was directed to the use of different concentrations of each different (immobilized) probe in one assay. This was found to be technically complex if not impossible on a chip surface. As a further option the substitution of ribonucleotides in an oligonucleotide composed of deoxyribonucleotides, and vice versa was applied for the adaptation of DNA stability, Hoheisel (1996), Nucleic Acids Res. 24, 430-432.
However, it may be also advantageous to increase the Tm of a given nucleic acid. This is interesting in the field of nucleic acids used for antisense therapy, mismatch discrimination and for nucleic acids used in diagnostics. The nucleic acids may be used as primers or probes. The aim is to allow a more simple design of primers and probes used in multiplex reactions and to synthesize shorter capture probes used on chips, as the chemical synthesis of oligonucleotides on a chip surface used for arrays is not as effective as in routine oligonucleotide synthesis. The relative contribution of each base pair to the melting temperature of a hybrid is the higher the shorter an oligonucleotide is. In consequence, the difference in stability between a mismatch and a perfect match is higher for shorter oligonucleotides. However, short oligonucleotides hybridize weakly and, therefore, the hybridization reaction has to be performed at low stringency. In consequence, the potential higher ability of discrimination between different sequences by shorter oligonucleotides can only be used under conditions of low stringency. It would be of considerable advantage to provide bases which allow to achieve a high level of mismatch discrimination under stringent conditions, in particular for short oligonucleotides at temperatures used e.g. in amplification reactions. Further, there is the desire in the state of the art to use short oligonucleotides with high discriminatory power in arrays as the chemical synthesis of oligonucleotides on solid supports used for arrays is not as effective as in routine synthesis. Therefore, the ability to use shorter oligonucleotides under stringent conditions would be of considerable advantage. If bases are found that lead to an increase of the Tm of an oligonucleotide hybridized to its complementary strand, other bases may then be used in the same oligonucleotide to further adjust the Tm according to the preferences of the test system to be used.
Theoretically, oligonucleotide duplexes forming other tridentate base pairs should exhibit a similar or higher stability, e.g. those with 2-aminoadenine opposite to thymine. Nevertheless, it has been shown that 2-aminoadenine-thyrine/uracil base pairs exhibit only a low thermal stability [4-10]. From the data published so far one can conclude that the additional NH2-group of 2′-deoxyadenosin-2-amine (molecule 1 (see below); n2Ad) contributes very little to the base pair stability of a DNA duplex. The Tm-increase is in the range of only 1-2° C. Furthermore, this stabilization does not correspond to the total number of n2 Ad-residues incorporated in the duplex instead of dA [11]. A stronger stabilization as reported for duplex DNA is found for duplex RNA or for DNA-RNA hybrids [9] [10] [12]. A rather high base pair stability is observed when 2-aminoadenine is introduced into PNA [13] or hexitol nucleic acids [14]. Modified backbones other than of DNA or of RNA appear to enhance the stability of the 2-aminoadenine-thymine/uracil pair.
The unusual behavior of oligonucleotide duplexes containing n2Ad-dT residues is interesting for the development of an adenine-thymine recognition motif showing the same or even a higher stability than a guanine-cytosine base pair. In the following compounds the purine moiety of compound 1 is replaced by an 8-aza-7-deazapurine (pyrazolo[3,4-d]pyrimidine) or a 7-deazapurine (pyrrolo[2,3-d]pyrimidine) leading to nucleosides (2a [15], 2b, 2c or 3 [16], [17] see below).

Compounds of similar chemical architecture were investigated in the prior art. The synthesis of 7-substituted-7-deaza and 8-aza-7-deazapurine 2′-deoxyribonucleotides, their incorporation into oligonucleotides, and the stability of the corresponding duplexes has been investigated (Seela et al. (1997) Nucleosides & Nucleotides 16, 963-966). This document does not contain a disclosure of 7-substituted 7-deaza-8-aza-diamino-purines. Stabilization of duplexes by pyrazolopyrinidine base analogues have been reported (Seela et al. (1988) Helv. Chim. Acta 71, 1191-1198; Seela et al. (1988) Helv. Chim Acta 71, 1813-1823; and Seela et al. (1989) Nucleic Acids Res. 17, 901-910)
Pyrazolo[3,4-d]pyrimidine residues in oligonucleotides are also useful as sites of attachment of various groups (WO90/14353). Oligonucleotides having incorporated one or more pyrazolo[3,4-d]pyrimidine have an enhanced tendency to form triplexes (Belousov et al. (1998). Nucleic Acids Res. 26, 1324-1328).
The compounds 7-iodo, 7-cyano and 7-propynyl-7-deaza-2-amino-2′-deoxyadenosine were synthesized by Balow et al. (1997, Nucleosides & Nucleotides 16, 941-944) and incorporated into oligonucleotide sequences. These oligonucleotides exhibit enhanced binding affinities to RNA complements relative to unmodified sequences. However, no corresponding 8-aza-compounds were made and investigated. Seela et al. (1999, Nucleosides & Nucleotides 18, 1399-1400) disclose 7-substituted 8-aza-7-deazapurine DNA, its synthesis and duplex stability. The authors do not address possible uses of the disclosed compounds.
WO 90/03370 discloses 3,4-disubstituted and 3,4,6-trisubstituted pyrazolo-[3,4-d]-pyrimidines, more particularly 4,6-diamino-pyrazolo-[3,4-d]-pyrimidines with a linker at the C3-position to which an intercalator, an electrophilic cross linker or a reporter group is attached. These compounds may be attached to sugars or incorporated into oligonucleotides and thereby used for the identification, isolation, localization and/or detection of complementary nucleic acid sequences of interest. U.S. Pat. No. 5,594,121 discloses novel oligomers with enhanced abilities to form duplexes or triplexes. The oligomers may contain 7-substituted 8-aza-7-deaza-diamino-purines with propinyl and aryls as substituents at the 7-position. Compositions containing these oligomers may used for diagnostic purposes.
There is still a need to provide probes with a high discriminatory power and with a short length, the Tm of which is high under stringent conditions and which can be used in various methods useful in the field of diagnostics as e.g. in the Lightcycler® system (Roche, Mannheim, Germany), TaqMan® (WO92/02638 and corresponding U.S. Pat. Nos. 5,210,015, 5,804,375, 5,487,972) or other applications involving fluorescence energy transfer.
Terms and Definitions
Conventional techniques of molecular biology and nucleic acid chemistry, which are within the skill of the art, are fully explained fully in the literature. See, for example, Sambrook et al., 1989, Molecular Cloning—A Laboratory Manual, Cold Spring Harbor Laboratory, Cold Spring Harbor, N.Y.; Oligonucleotide Synthesis (M. J. Gait, ed., 1984); Nucleic Acid Hybridization (B. D. Hames and S. J. Higgins. eds., 1984); and a series, Methods in Enzymology (Academic Press, Inc.), all of which are incorporated herein by reference. All patents, patent applications, and publications mentioned herein, both supra and infra, are incorporated herein by reference The terms "nucleic acid" and "oligonucleotide" refer to polydeoxyribonucleotides (containing 2-deoxy-D-ribose), to polyribonucleotides (containing D-ribose), and to any other type of polynucleotide which is an N glycoside of a purine or pyrimidine base, or modified purine or pyrimidine base. There is no intended distinction in length between the terms "nucleic acid" and "oligonucleotide", and these terms will be used interchangeably. These terms refer only to the primary structure of the molecule. Thus, these terms include double- and single-stranded DNA, as well as double- and single-stranded RNA. The term "polynucleotide" shall be used interchangably for "nucleic acid".
The term "backbone" or "nucleic acid backbone" for a nucleic acid binding compound according to the invention refers to the structure of the chemical moiety linking nucleobases in a nucleic acid binding compound. The bases are attached to the backbone and take part in base pairing to a complementary nucleic acid binding compound via hydrogen bonds. This may include structures formed from any and all means of chemically linking nucleotides, e.g. the natural occurring phosphodiester ribose backbone or unnatural linkages as e.g. phosphorthioates, methyl phosphonates, phosphoramidates and phosphortriesters. Peptide nucleic acids have unnatural linkages. Therefore, a "modified backbone" as used herein includes modifications to the chemical linkage between nucleotides as described above, as well as other modifications that may be used to enhance stability and affinity, such as modifications to the sugar structure. For example an α-anomer of deoxyribose may be used, where the base is inverted with respect to the natural β-anomer. In an embodiment, the 2′-OH of the sugar group may be altered to 2′-O-alkyl or 2′-O-alkyl-n(O-alkyl), which provides resistance to degradation without comprising affinity. An unmodified nucleotide sequence having a phosphodiester backbone is "comparable" to a nucleobase-containing sequence having a modified backbone if the two sequences have identical base sequencing. Thus, the backbones of such sequences are also comparable.
The term "nucleic acid binding compound" refers to substances which associate with nucleic acids of any sequence and are able to function as binding partner to a substantially complementary nucleic acid. The binding preferably occurs via hydrogen bonding between complementary base pairs when the nucleic acid binding compound is in a single-stranded form. Preferably, non-natural bases, the subject of the invention, attached to the backbone of the nucleic acid binding compound may be also involved in hydrogen-bonding, however, these may also be able to form hydrogen bonds to only some or all natural occurring bases as e.g. inosine. The expert in the field recognizes that the most well-known "nucleic acid binding compounds" are nucleic acids as DNA or RNA.
The term "probe" refers to synthetic or biologically produced nucleic acids (DNA or RNA) which, by design or selection, contain specific nucleotide sequences that allow them to hybridize under defined predetermined stringencies, specifically (i.e., preferentially) to target nucleic acids. A "probe" can be identified as a "capture probe" meaning that it "captures" the target nucleic acid so that it can be separated from undesirable materials which might obscure its detection. Once separation is accomplished, detection of the captured target nucleic acid can be achieved using a suitable procedure. "Capture probes" are often already attached to a solid phase.
The term "hybridization" refers the formation of a duplex structure by two single-stranded nucleic acids due to complementary base pairing. Hybridization can occur between fully complementary nucleic acid strands or between "substantially complementary" nucleic acid strands that contain minor regions of mismatch. Conditions under which only fully complementary nucleic acid strands will hybridize are referred to as "stringent hybridization conditions" or "sequence-specific hybridization conditions". Stable duplexes of substantially complementary sequences can be achieved under less stringent hybridization conditions; the degree of mismatch tolerated can be controlled by suitable adjustment of the hybridization conditions. Those skilled in the art of nucleic acid technology can determine duplex stability empirically considering a number of variables including, for example, the length and base pair concentration of the oligonucleotides, ionic strength, and incidence of mismatched base pairs, following the guidance provided by the art (see, e.g., Sambrook et al., 1989, Molecular Cloning—A Laboratory Manual, Cold Spring Harbor Laboratory, Cold Spring Harbor, N.Y.; and Wetmur, 1991, Critical Review in Biochem. and Mol. Biol. 26(3/4):227-259; both incorporated herein by reference).
The term "primer" refers to an oligonucleotide capable of acting as a point of initiation of DNA synthesis under conditions in which synthesis of a primer extension product complementary to a nucleic acid strand is induced, i.e., either in the presence of four different nucleoside triphosphates and an agent for extension (e.g., a DNA polymerase or reverse transcriptase) in an appropriate buffer and at a suitable temperature. As used herein, the term "primer" is intended to encompass the oligonucleotides used in ligation-mediated amplification processes, in which one oligonucleotide is "extended" by ligation to a second oligonucleotide which hybridizes at an adjacent position. Thus, the term "primer extension", as used herein, refers to both the polymerization of individual nucleoside triphosphates using the primer as a point of initiation of DNA synthesis and to the ligation of two primers to form an extended product. A primer is preferably a single-stranded DNA. The appropriate length of a primer depends on the intended use of the primer but typically ranges from 6 to 50 nucleotides. Short primer molecules generally require cooler temperatures to form sufficiently stable hybrid complexes with the template. A primer need not reflect the exact sequence of the template nucleic acid, but must be sufficiently complementary to hybridize with the template. The design of suitable primers for the amplification of a given target sequence is well known in the art and described in the literature cited herein. Primers can incorporate additional features which allow for the detection or immobilization of the primer but do not alter the basic property of the primer, that of acting as a point of initiation of DNA synthesis. For example, primers may contain an additional nucleic acid sequence at the 5′ end which does not hybridize to the target nucleic acid, but which facilitates cloning of the amplified product. The region of the primer which is sufficiently complementary to the template to hybridize is referred to herein as the hybridizing region.
The terms "target, "target sequence", "target segment", "target region", and "target nucleic acid" refer to a region or subsequence of a nucleic acid which is to be amplified or investigated.
As used herein, a primer is "specific" for a target sequence if the number of mismatches present between the primer sequence and the target sequence is less than the number of mismatches present between the primer sequence and non-target sequences which may be present in the sample. Hybridization conditions can be chosen under which stable duplexes are formed only if the number of mismatches present is no more than the number of mismatches present between the primer sequence and the target sequence. Under such conditions, the primer can form a stable duplex only with a target sequence. Thus, the use of target-specific primers under suitably stringent amplification conditions enables the specific amplification of those target sequences which contain the target primer binding sites. The use of sequence-specific amplification conditions enables the specific amplification of those target sequences which contain the exactly complementary primer binding sites.
Halogen means a fluoro, chloro, bromo or iodo group. The most preferred halogen groups are —I and —Br.
Alkyl groups are preferably chosen from alkyl groups containing from 1 to 10 carbon atoms, either arranged in linear, branched or cyclic form. The actual length of the alkyl group will depend on the steric situation at the specific position where the alkyl group is located. If there are steric constraints, the alkyl group will generally be smaller, the methyl and ethyl group being most preferred. All alkyl, alkenyl and alkynyl groups can be either unsubstituted or substituted. Substitution by hetero atoms as outlined above, will help to increase solubility in aqueous solutions.
Alkenyl groups are preferably selected from alkenyl groups containing from 2 to 10 carbon atoms. For the selections similar considerations apply as for alkyl groups. They also can be linear, branched and cyclic. The most preferred alkenyl group is the ethylene group.
Alkynyl groups have preferably from 2 to 10 carbon atoms. Again, those carbon atoms can be arranged in linear, branched and cyclic manner. Further, there can be more than one triple bond in the alkynyl group. The most preferred alkynyl group is the 3-propargyl-group.
Alkoxy groups preferably contain from 1 to 6 carbon atoms and are attached to the rest of the moiety via the oxygen atom. For the alkyl group contained in the alkoxy groups, the same considerations apply as for alkyl groups. The most preferred alkoxy group is the methoxy group.
By "aryl" and "heteroaryl" (or "heteroaromatic") is meant a carbocyclic or heterocyclic group comprising at least one ring having physical and chemical properties resembling compounds such as an aromatic group of from 5 to 6 ring atoms and comprising 4 to 20 carbon atoms, usually 4 to 9 or 4 to 12 carbon atoms, in which one to three ring atoms is N, S or O, provided that no adjacent ring atoms are O—O, S—S, O—S or S—O. Aryl and heteroaryl groups include, phenyl, 2-, 4- and 5-pyrimidinyl, 2-, 4- and 5-thiazoyl, 2-s-triazinyl, 2-, 4-imidazolyl, 2-, 4- and 5-oxazolyl, 2-, 3- and 4-pyridyl, 2- and 3-thienyl, 2- and 3-furanyl, 2- and 3-pyrrolyl optionally substituted preferably on a ring C by oxygen, alkyl of 1-4 carbon atoms or halogen. Heteroaryl groups also include optional substitution on a ring N by alkyl of 1-4 carbon atoms or haloalkyl of 1-4 carbon atoms and 1-4 halogen atoms. Exemplary substituents on the aryl or heteroaryl group include methyl, ethyl, trifluoromethyl and bromo. Such substituted aryl and heteroaryl groups include benzyl and the like. "Heteroaryl" also means systems having two or more rings, including bicyclic moieties such as benzimidazole, benzotriazole, benzoxazole, and indole. Aryl groups are the phenyl or naphtyl moiety, either unsubstituted or substituted by one or more of amino, -cyano, -aminoalkyl, —O—(C1-C10)-alkyl, —S—(C1-C10)-alkyl, —(C1-C10)-alkyl, sulfonyl, sulfenyl, sulfinyl, nitro and nitroso. Most preferred aryl group is the phenyl group. Preferred arylalkyl group is the benzyl group. The preferred alkylamino group is the ethylamino group. The preferred —COO(C1-C4) alkyl group contains one or two carbon atoms in the alkyl moiety (methyl or ethyl esters). Other aryl groups are heteroarylgroups as e.g. pyrimidine, purine, pyrrol, or pyrazole. Aryl and heteroaryl. According to the present invention the term aryl shall also include all heteroaryls.
Aryloxy groups preferably contain from 6 to 20 carbon atoms. Those carbon atoms may be contained in one or more aromatic rings and further in side chains (for example, alkyl chains) attached to the aromatic moiety. Preferred aryloxy groups are the phenoxy and the benzoxy group.
A "protecting group" is a chemical group that is attached to a functional moiety (for example to the oxygen in a hydroxyl group or the nitrogen in an amino group, replacing the hydrogen) to protect the functional group from reacting in an undesired way. A protecting group is further defined by the fact that it can be removed without destroying the biological activity of the molecule formed, here the binding of the nucleic acid binding compound to a nucleic acid. Suitable protecting groups are known to a man skilled in the art. Especially preferred protecting groups for example for hydroxyl groups at the 5′-end of a nucleotide or oligonucleotide are selected from the trityl groups, for example dimethoxytrityl. Preferred protecting groups at exocyclic amino groups in formula I are acyl groups, most preferred the benzoyl group (Bz), phenoxyacetyl or acetyl or formyl, and the amidine protecting groups as e.g. the N,N-dialkylformamidine group, preferentially the dimethyl-, diisobutyl-, diisobutyryl and the di-n-butylformamidine group. Preferred O-protecting groups are the aroyl groups, the diphenylcarbamoyl group, the acyl groups, and the silyl groups. Among these most preferred is the benzoyl group. Preferred silyl groups are the trialkylsilyl groups, like, trimethylsilyl, triethylsilyl and tertiary butyl-dimethyl-silyl. Another preferred silyl group is the trimethylsilyl-oxy-methyl group (TOM)(Swiss Patent Application 01931/97). Further, preferred protecting groups are groups as ortho nitro-benzyl protecting groups like 2-(4-nitrophenyl)ethoxycarbonyl (NPEOC) or photoactivable compounds as 2-nitrophenylpropyloxycarbonyl (NPPOC) (Giegrich et al., Nucleosides & Nucleotides 1998, 17, 1987). According to the invention, also the phthaloyl group may be used as protecting group.
Any atom in the definitions within the formulae presented herein is not limited to a specific isotope. Thus, a phosphorus atom (P) can either mean the regular 31P or the radioactive 32P or a mixture thereof. The same applies for hydrogen (H/D/T), carbon (C), iodine (Cl, Br, I) and nitrogen (N).
During chemical synthesis, any reactive groups as e.g. —OH, —SH, —NH2, —NH-alkyl, —NH-alkenylene, —NH-alkynylene, or —NH-aryl (including those groups in reporter groups) should be protected by suitable protecting groups, i.e. that the present invention contemplates compounds for the synthesis of olignucleotides wherein the formulas or substituents are chosen with the proviso that one or two hydrogen atoms of any —OH, —SH, —NH2, —NH-alkyl, —NH-alkenylene, —NH-alkynylene, or —NH-aryl group are substituted by a protecting group. Further, during chemical synthesis, the compound will be attached for convenience to a solid phase. In these cases, the definitions of the substituents given above will be selected accordingly.
Reporter groups are generally groups that make the nucleic acid binding compound as well as any nucleic acids bound thereto distinguishable from the remainder of the liquid, i.e. the sample (nucleic acid binding compounds having attached a reporter group can also be termed labeled nucleic acid binding compounds, labeled probes or just probes). The term reporter group and the specific embodiments preferably include a linker which is used to connect the moiety intended to be used (the actual solid phase or the fluorophoric moiety) to the position of attachment as the reporter group. The linker will provide flexibility such that the nucleic acid binding compound can bind the nucleic acid sequence to be determined without major hindrance by the solid phase. Linkers, especially those that are not hydrophobic, for example based on consecutive ethylenoxy units, for example as disclosed in DE 3943522 are known to a man skilled in the art.
By "array" is meant an arrangement of addressable locations on a device. The locations can be arranged in two dimensional arrays, three dimensional arrays, or other matrix formats. The number of locations can range from several to at least hundreds of thousands. Most importantly, each location represents a totally independent reaction site. Each location carries a nucleic acid binding compound which can serve as a binding partner for a second nucleic acid binding compound, a nucleic acid, in particular a target nucleic acid.
The term "building block" or "subunit" refers to a compound which can be used in oligonucleotide synthesis wherein subsequently single building blocks are chemically linked to form a more complex structure, i.e. an oligonucleotide precursor. Examples for building blocks are phosphoramidites or phosphonates.
The term "substituted compound" shall mean that a compound carries further chemical groups, moieties or substituents other than the compound itself. These substituents shall in principle include but are not limited to halogens or alkyl, alkenyl, alkynyl, or aryl compounds optinally substituted with further heteroatoms

Nucleic acid binding compounds containing pyrazolo[3,4-d]pyrimidine analogues of purin-2,6-diamine and their uses


A bearing apparatus includes a rotator body, a non-rotation body rotatably supporting the rotator body, and a lubrication fluid provided between the rotator body and the non-rotation body in which the rotator body is supported in a thrust direction by a thrust dynamic pressure bearing formed between the rotator body and the non-rotation body. The bearing apparatus includes an active magnetic bearing formed by a driving coil disposed on one of the rotator body and the non-rotation body and a magnet disposed on the other thereof, and a gap sensor that detects an axial direction gap between the rotator body and the non-rotation body. The thrust dynamic pressure bearing and the active magnetic bearing are combined such that the static rigidity of the bearing apparatus is born by the active magnetic bearing and the dynamic rigidity is born by the dynamic pressure bearing.

1. Field of the Invention
The present invention relates to a bearing apparatus having a rotator body and a non-rotation body in which the rotator body is supported in a thrust direction by a thrust dynamic pressure generated between thrust bearing surfaces of the rotator body and the non-rotation body, which is applicable as, for example, a bearing apparatus of a hard disc drive motor, and a variety of optical disc drive motors.
2. Description of Related Art
A variety of strict demands in higher accuracy at higher speeds, longer service life, and lower noise are imposed on small size spindle motors that are used for hard disc drive apparatuses and various optical disc drives. To meet the demands, it is effective to make bearing apparatuses with dynamic pressure bearings. In this connection, a bearing apparatus in which its radial bearing and thrust bearing are both formed by dynamic pressure bearings has been developed.
A typical dynamic pressure bearing uses a lubrication fluid filled in a minute gap between a rotator body and a non-rotation body and generates a pressure by a shearing force caused by the lubrication fluid to support the rotator body in a non-contact manner. Therefore, it is essential to work parts at a high level of precision and assemble them at a high level of precision in order to provide and maintain a minute gap between the rotator body and the non-rotation body.
With high precision machine tools, a radial dynamic pressure bearing can be relatively readily manufactured with high precision, and its required assembly accuracy can be relatively readily achieved. However, for a thrust dynamic bearing, much strict accuracy is required since a flange shaped thrust plate needs to be assembled on a rotator shaft, and a level of precision in the order of xcexcm needs to be secured in the assembly work. Also, since a thrust dynamic bearing supports the weight in the direction of gravity, the rotator body may often contact the non-rotation body when the rotation is stopped, which results in shortening the service life of the bearing apparatus, and also the service life of the motor.
To solve the problems described above, a bearing apparatus is provided with a radial bearing that is formed from a dynamic pressure bearing and a thrust bearing that is formed from a magnetic bearing.
However, the thrust bearing formed from a magnetic bearing has the following problems.
When the magnetic bearing is a controlled type to maintain the position of the rotator body in its axial direction constant, electric power needs to be constantly supplied. As a result, the motor suffers a large amount of losses.
Since the magnetic force is relatively small compared to the dynamic pressure, the rotator body would likely contact the non-rotation body by impact forces.
Since the magnetic force is relatively small compared to the dynamic pressure, the bearing apparatus tends to become larger in size to obtain a predetermined supporting force in the thrust direction.
Since the magnetic bearing has a lower dynamic rigidity compared to the dynamic pressure bearing, it is rather vulnerable to high frequency vibrations compared to the dynamic pressure bearing.
The present invention has been made to solve the problems of the conventional art describe above.
It is an object of the present invention to provide a bearing apparatus having an active magnetic bearing that requires electrical power that is used only to control vibration components. As a result, the bearing apparatus in accordance with the present invention reduces the power consumption, securely prevents contacts between a rotator body and a non-rotation body and substantially extends the service life of the bearing apparatus.
It is another object of the present invention to provide a bearing apparatus that may include a thrust dynamic pressure bearing and an active magnetic bearing provided in combination such that characteristics of the respective bearings are effectively used. For example, the static rigidity is born by the active magnetic bearing and the dynamic rigidity is born by the dynamic pressure bearing. As a result, the bearing apparatus has a higher accuracy and a longer service life and can reduce the load torque at the time of starting its rotation, compared to a bearing apparatus that uses only a thrust dynamic pressure bearing or an active magnetic bearing.
It is still another object of the present invention to provide a bearing apparatus that may include a thrust dynamic pressure bearing and an active magnetic bearing used in combination. In one aspect of the present embodiment, the load applied to the dynamic pressure bearing is reduced compared to a bearing apparatus that uses only a dynamic pressure bearing, the distance of a fine gap that forms the dynamic pressure bearing can be made relatively large, the need to strictly manage the working precision and assembly accuracy for parts of the dynamic pressure bearing can be eliminated, and the manufacturing cost is lowered.
In accordance with an embodiment of the present invention, a bearing apparatus includes a rotator body, a non-rotation body rotatably supporting the rotator body, and a lubrication fluid present between the rotator body and the non-rotation body in which the rotator body is supported in a thrust direction by a thrust dynamic pressure bearing formed between the rotator body and the non-rotation body. The bearing apparatus comprises an active magnetic bearing formed by a driving coil disposed on one of the rotator body and the non-rotation body and a magnet disposed on the other thereof, and a gap sensor that detects an axial direction gap between the rotator body and the non-rotation body, wherein the axial direction gap is controlled by controlling current applied to the driving coil based on an output of the gap sensor.
Other features and advantages of the invention will be apparent from the following detailed description, taken in conjunction with the accompanying drawings that illustrate, by way of example, various features of embodiments of the invention.


An element comprising a non-stick surface for substantially cleanly removing a product which is arranged against said non-stick surface. The element comprises a first layer of an pervious material, which is configured to allow a fluid to flow there through. An outer surface of said first layer provides the non-stick surface. The element comprises a second layer of an impervious material, which is configured to substantially block a flow of fluid there through. The second layer is arranged at a side of said first layer opposite to the outer surface. The element comprises ducts or chambers which are arranged in said first layer or in between said first and second layer. Said ducts or chambers are arranged in fluid connection with said pervious material and are configured for feeding a pressurized fluid to the pervious material. At least the first layer is formed using a three-dimensional printing tool.

The invention relates to an element comprising a non-stick surface for substantially cleanly removing a product which is arranged against said non-stick surface. The invention further relates to a method for producing such an element with a non-stick surface by means of a three-dimensional printer.
A non-stick surface is a surface engineered to reduce the ability of other materials to stick to it. An area where non-stick surfaces is frequently used is the food industry. For example in industrial bakery technology for the production of bread, baguette, cake, ciabatta, pizza, puff pastry, rolls, buns and cookies, pieces of dough transported to and handled at various handling stations on top of proofing trays and/or baking trays. Such trays are commonly provided with anti-adhesion or non-stick coating based on fluoropolymers or rubber silicones.
A disadvantage of using such known anti-adhesion or non-stick coatings is, that due to wear during the use of such trays, abrasion or damaging of the non-stick coating may occur and regular re-coating of the trays is required.
It is an object of the present invention to least partially solve the above identified disadvantage and/or to provide an alternative element with non-stick surface. It is further an object of the present invention to provide a method for producing such an element, preferably using a three-dimensional printing technique.

Element comprising a non-stick surface and method for three-dimensional printing such an element


A system and method for sharing electronic data between participants of a phone conference, such as an online presentation, without a need to exchange passwords to link two devices together for data transfer nor go through a login procedure to access the data resource. To achieve this, the participants use a device or software application that samples the audio of the phone conversation and creates a stream of audio fingerprints. The streams of fingerprints are sent to a matching service on the internet. This matching service finds the fingerprints that correspond to the same conversation among the streams of simultaneous users. Once a match is found with a high enough confidence level, the matching service exchanges identifiers such as public IP addresses and sends those back to the fingerprinting units. When instructed by the user, the units can then proceed to setup a secure data connection.

When two or more persons having a phone conference, want to share electronic data or media content with possibly confidential or private information, such as a document, a picture, or a presentation, they need to setup an additional communication channel. This is typically done over a computer data network.
The setup of such a secure communication channel over an insecure computer data network is cumbersome and vulnerable to attacks. There are two problems to be solved: (a) how do the endpoints find each other on the network? This is connectivity issue. And (b) how can it be really known that the connection is genuine and not an impersonator? This is an authentication problem.
The connectivity issue can be solved by using conventional peer-to-peer or client-server connection setup techniques. The authentication issue is more difficult to solve.
Encryption protocols include an authenticated key exchange phase and it is this first step that is the most vulnerable and also the most annoying.
Authenticated key exchange depends either on a shared secret or on a trusted third party such as a public certification authority. But using a trusted third party still requires an authentication phase: one has to prove his identity via login and passwords, so this doesn't help.
Relying on a pre-shared secret is also unsuitable, because it requires a special exchange step prior to the phone conversation. This is unsuitable for ad-hoc communications between people who may never have met.
Any system requiring passwords or pre-shared secrets is vulnerable to attacks. Secrets and passwords can be stolen or lost and certificates can be forged.
A common secret could be generated ad hoc and can be communicated over the phone, but this process is again not user friendly. It's annoying and intrusive. The secret could be exchanged via another out-of-band channel such as email or fax. However, this method has the same problems as above and also requires the participants to make additional steps, such as opening email clients, communicating email addresses, etc. In addition, these methods are susceptible to eavesdropping. Telephone connections or email messages are insecure ways of communication that are easily compromised.
Several methods have been devised to generate an ad hoc secret and communicate this over the phone to the participants. Some methods use watermarking techniques to hide the secret in an audible signal. However, phone connections are not well suited to robustly transmit metadata, without being very intrusive and hinder the normal conversation. The secret also needs to be repeated to late-comers. And a login procedure prior or during the call is still required to protect against eavesdropping, with again the same problems regarding ease of use and security.
The fundamental problem of all automatic authentication methods is that they use keys or passwords that are in no way related to the way that human beings use to identify and authenticate each other. So, setting up an additional electronic communication channel, naturally requires another secret password, at some stage or another, for authentication.
The problem thus is finding a way to extend this robust manual authentication method to the second, electronic communication channel, in an ad-hoc, transparent and robust way.
WO 2013/138651 describes a method to allow authorization of computing device association using human-perceptible signals. The method includes forming an association between a first computing device and a second computing device, computing with the first computing device a fingerprint of a common key derived during forming of the association, and emitting with the first computing device a first audio stimulus based upon the computed fingerprint. The first audio stimuli is at least one octave number apart from a second audio stimuli of the second computing device emitted by the second computing device based upon the common key. Accordingly the first computing device is configured to emit human perceptible sounds, i.e. to emit a first audio stimulus based upon the computed fingerprint. A second audio stimulus is emitted by the second computing device based on the common key. If a simultaneous playback of both sequences is harmonious, the common key was exchanged, if it is discordant the devices failed to exchange a common key.
US 2003/0135740 describes a network based mechanism for real time verification and authentication of data and user identities. Biometric elements, such as voice prints, are utilized to enhance the Public Key Infrastructure as a means to decrypt data and verify data authenticity, such that the user's private key is authenticated remotely on a one-time basis. An authentication server has various software modules that enable authentication of user identity, secure user access to data, digital signatures, secure messaging and secure online transactions.

This patent is subject to a terminal disclaimer.

Ad hoc one-time pairing of remote devices using online audio fingerprinting


Provided is an apparatus provided in a working machine to lower a load, comprising a hydraulic pump, a hydraulic actuator, a manipulation device having a manipulation member, a meter-in flow control device, a meter-out flow control device, a back pressure valve, a regeneration fluid passage branched from the meter-out fluid passage at a position upstream of the back pressure valve and merged with the meter-in fluid passage, and a check valve. The meter-in flow control device controls a meter-in flow rate in a region of the meter-in fluid passage upstream of a merging point with the regeneration fluid passage. The meter-out flow control device controls a meter-out flow rate in a region of the meter-out fluid passage upstream of a branching point of the regeneration fluid passage so as to make the meter-out flow rate be greater than the meter-in flow rate.

1. Field of the Invention
The present invention relates to a hydraulic driving apparatus provided in a working machine, such as a crane, to move a load, such as a suspended load.
2. Description of the Background Art
As a hydraulic driving apparatus provided in a working machine, there is known a type equipped with a hydraulic actuator, as described, for example, in JP 2000-310201 A, which will be called "Patent Document 1" below. In this type, the hydraulic actuator can be operated to move a load in the same direction as a self-weight falling direction which is a direction along which the load falls by its self-weight. Patent Document 1 discloses a lowering hydraulic circuit for operating a hydraulic motor serving as the hydraulic actuator, to move a suspended load in a lowering direction.
In the above working hydraulic driving apparatus, cavitation is likely to occur during a lowering drive mode in which the hydraulic motor is driven (operated) in a rotational direction corresponding to the lowering direction. Specifically, during the lowering drive mode, the self-weight of the suspended load increases the rotational speed of the hydraulic motor, which may cause a flow rate adsorbed by the hydraulic motor to be greater than a flow rate of hydraulic fluid supplied from a hydraulic pump to the hydraulic motor. This may lower a pressure of a meter-in fluid passage which is a fluid passage on a hydraulic fluid supply side of the hydraulic motor, namely a meter-in pressure, to generate cavitation in the meter-in fluid passage. The cavitation possibly steals a braking force from the hydraulic motor and possibly causes falling of the suspended load.
To suppress cavitation thus generated in a meter-in fluid passage, Patent Document 1 discloses an external pilot-operated counterbalance valve (hereinafter referred to simply as "counterbalance valve") provided in a meter-out fluid passage, that is, a fluid passage on a hydraulic fluid discharge side of the hydraulic motor (counterbalance valve 11 in FIG. 1 of Patent Document 1). The counterbalance valve is applied with a meter-in pressure as a pilot pressure and applied with a set pressure P1 thereof by means of a spring or the like. The counterbalance valve has a variable valve opening degree, which is increased when the meter-in pressure becomes greater than the set pressure P1 while reduced when the meter-in pressure becomes lower than the set pressure P1. The counterbalance valve narrows down the meter-out fluid passage when the valve opening degree is reduced, thus producing a braking force in the hydraulic motor to decelerate the hydraulic motor and thereby suppress the flow rate adsorbed by the hydraulic motor. The counterbalance valve thus keeps the meter-in pressure to the set pressure P1 or below, thereby suppressing the cavitation in the meter-in fluid passage.
FIG. 16 shows a conventional working hydraulic driving apparatus 701, which comprises an external pilot-operated counterbalance valve 784. The counterbalance valve 784 has a measurement point on the meter-in fluid passage 30 and a control point is located on the meter-out fluid passage 40; these forms an unstable control system which is not co-located under the control theory.
This unstable control system is likely to cause hunting in rotational speed of the hydraulic motor 13. For example, when a manipulation lever 16 shown in FIG. 16 is manually operated from a neutral position to a lowering position thereof at a time T0, an amount of hydraulic fluid to be supplied to the hydraulic motor 13 through a direction selector valve 20 is increased according to the manual operation, thus increasing a meter-in pressure of the meter-in fluid passage 30. The counterbalance valve 784, detecting the increase in the meter-in pressure, is operated in a valve-opening direction; however, the difference between the measurement point and the control point of the counterbalance valve 784 intends to cause a time lag from a change in the meter-in pressure to a real movement of the valve spool of the counterbalance valve 784. This time lag repetitively increases and reduces the valve opening degree of the counterbalance valve 784 as shown in FIG. 17A, thereby oscillating the meter-in pressure as shown in FIG. 17B. This results in a possibility of an oscillation in rotational speed of the hydraulic motor 13 (see FIG. 16), that is, a hunting.
As means for suppressing such hunting, it is conceivable to provide an orifice 786 shown in FIG. 16 in a pilot line 785 for the counterbalance valve 784. The orifice 786 makes the counterbalance valve 784 be gradually opened according to an increase in the meter-in pressure. In other words, the orifice 786 provides attenuation to a movement of the counterbalance valve 784 in a direction from a closed state to an opened state, thereby making a response of the valve 784 slow.
The orifice 786, however, generates flow resistance due to the throttle of the meter-out fluid passage by the counterbalance valve 784, until the counterbalance valve 784 will have reached an adequate valve opening degree A1 as shown in FIG. 18A, thereby possibly generating an unnecessary boosted pressure in the meter-in fluid pressure 30, as indicated by the shadow area in FIG. 18, which possibly results in deteriorated fuel economy.
Patent Document 1 discloses a technique of providing a flow regulation valve in order to suppress the hunting. This flow regulation valve is operable to control a flow rate in the meter-in fluid passage so as to reduce the pressure difference between the meter-in fluid passage and the meter-out fluid passage. This however causes a problem that an operating speed (lowering speed) of the hydraulic motor is largely varied depending on a mass of the load. The reason is as follows.
When a hydraulic driving apparatus is operated in a direction to move a load downward, i.e., in a lowering direction, a holding pressure appropriate for a mass of the load is generally produced in a meter-out fluid passage. This holding pressure becomes higher when the load is relatively heavy, than when the load is relatively light. The flow regulation valve disclosed in the Patent Document 1 opens more largely as the holding pressure becomes higher. This increases a flow rate in the meter-in fluid passage, that is, a meter-in flow rate, and operating speed of the hydraulic motor. Hence, the lowering speed becomes higher in the case of a relatively heavy load than in the case of a relatively light load. In other words, even if a manipulation lever is not changed, the operating speed of the hydraulic motor can be varied depending on a level of weight of the load. This deteriorates operability.
JP 10-267007 A, which will be called Patent Document 2 below, discloses a regeneration circuit, for example, shown in FIG. 5 of Patent Document 2. This regeneration circuit comprises an orifice provided in a meter-out fluid passage and a regeneration fluid passage for communicating an upstream side of the orifice and a meter-in fluid passage. The regeneration circuit allows a part of hydraulic fluid flowing through the meter-out fluid passage to be returned to the meter-in fluid passage through the regeneration fluid passage, thereby increasing respective operating speeds of a hydraulic actuator and an attachment adapted to be driven by the hydraulic actuator.
If the regeneration circuit disclosed in Patent Document 2 were applied to a circuit where a hydraulic motor is used to lower a suspended load as disclosed in the Patent Document 1, a flow rate in the regeneration fluid passage (regeneration flow rate) would be increased along with an increase in weight of the suspended load. This makes the lowering speed become higher as the suspended load becomes heavier, resulting in a loss of safety and operability. Moreover, the technique disclosed in the Patent Document 2, which does not compensate for a minimum pressure of the meter-in fluid passage, has a possibility of cavitation in the meter-in fluid passage, which may cause the hydraulic motor to stall.

Hydraulic driving apparatus for working machine


The present invention pertains to a process for preparing a compound of Formula I that is achiral, racemic or enantiomerically enriched at the hydroxylation center indicated by comprising contacting a compound of Formula II with an oxidant selected from oxygen, hydrogen peroxide, peracids or alkyl hydroperoxides in the presence of a zirconium complex, wherein R1, R2 and R3 are as defined in the disclosure. This invention also pertains to zirconium complexes useful in this procedure comprising zirconium and a ligand of Formula III or its enantiomer wherein J, R6 and n are as defined in the disclosure. This invention further pertains to a compound of Formula III or its enantiomer.

Certain β-dicarbonyl compounds (i.e. β-keto esters and their hydroxylated derivatives) are useful as intermediates for the preparation of fine chemicals, pharmaceuticals and plant protection products such as arthropodicidal oxadiazines. Ardiropodicidal oxadiazines are disclosed in PCT Publications WO 92/11249 and WO 93/19045. Methods of preparing these compounds have also been reported in WO 95/29171, including a preparative step involving the hydroxylation of β-keto esters. However, improved preparative methods for these compounds are desirable for more economic commercial operation. Accordingly, the present invention provides an improved process to prepare hydroxylated β-dicarbonyl compounds, including those usefull in preparing arthropodicidal oxadiazines.

Hydroxylation of β-dicarbonyls with zirconium catalysts


An optical glucose sensor comprising: a sensing region comprising a boronic acid receptor for binding to glucose and a fluorophore associated with said receptor; an optical waveguide for directing incident light onto the sensing region; and a hydrophilic, polymeric, glucose-permeable barrier layer which is provided on at least a part of the sensing region; wherein the sensor is adapted so that glucose enters the sensing region of the sensor through said barrier layer.

It has been known for some time that boronates form reversible 5 membered ring complexes with saccharides. More recently, this property of boronates has been utilised in the development of sensors for the measurement of glucose in biological fluids. For example, a sensor may comprise a glucose receptor (the boronic acid) and a fluorophore that acts as the transmitter of the signal. These indicator chemistries can readily be immobilised onto an optical fibre of appropriate diameter, which can then be placed into body fluids or tissue to measure glucose.
It has been known for some time that boronic acids reversibly complex with glycoylated and glycated proteins. Although attempts have been made to devise sensing boronic acid chemistries that are selective it is obvious that glycated proteins represent potential interferents in the determination of glucose in body fluids when boronic acids are used as the sensor. Also other middle to high molecular weight endogenous materials have the potential to interfere with the boronic acid receptor by acting as quenchers of the transmitting fluorophore. There is therefore a need for a means to eliminate these interferents from a glucose sensor using boronic acid/fluorophore indicating chemistry.


A martensitic steel for a line pipe having excellent corrosion resistance and weldability is disclosed. The martensitic steel contains about:. 0.02 wt % or less of C, 0.50 wt % or less of Si, PA1 0.2 to 3.0 wt % of Mn, 10 to 14 wt % of Cr, PA1 0.2 to 7.0 wt % of Ni, 0.2 to 5.0 wt % of Mo, PA1 0.1 wt % or less of Al, 0.07 wt % or less of N, and PA1 the balance being Fe and incidental impurities; and PA1 about 0.006 wt % or less of Ca, and. these elements satisfy substantially the following equations: EQU (Cr %)+(Mo %)+0.1(N %)-3(C %).gtoreq.12.2, EQU (Cr %)+3.5(Mo %)+10(N %)+0.2(Ni %)-20(C %).gtoreq.14.5, and EQU 150(C %)+100(N %)-(Ni %)-(Mn %).ltoreq.4.. The martensitic steel may further contain at least one element selected from the group consisting of. about 2.0 wt % or less of Cu, about 0.15 wt % or less of Ti, about 0.15 wt % or less of Zr, about 0.15 wt % or less of Ta and. these elements satisfy substantially the following equations: EQU (Cr %)+(Mo %)+0.1(N %)+3(Cu %)-3(C %).gtoreq.12.2, EQU (Cr %)+3.5(Mo %)+10(N %)+0.2(Ni %)-20(C %).gtoreq.14.5, EQU 150(C %)+100(N %)-(Ni %)-(Mn %).ltoreq.4.

1. Field of the Invention
The present invention relates to a martensitic steel suitable for transfer steel pipes of oil and natural gas, and having excellent corrosion resistance and weldability.
2. Description of the Related Art
Oil and natural gas supplies have been almost exhausted from easily accessible wells in mild environments, and recent wells must be built in challenging environments, such as severely corrosive environments, cold environments, or in deep wells or in submarine oil fields. Therefore, superior characteristics are required of steel materials used in tubular goods and line pipes in such challenging oil producing regions.
For example, many wells contain large amounts of carbon dioxide gas; carbon steel is highly corroded in such an environment. In order to prevent carbon steel from corroding, inhibitors are injected into pipeline. However, use of inhibitors increases construction and maintenance costs of wells. Further, such inhibitors are not satisfactorily effective at high temperatures. Thus, the recent trend is toward use of corrosion-resistant materials instead of relying on use of inhibitors.
Among corrosion-resistant materials for tubular goods, martensitic stainless steel containing 13 percent by weight (hereinafter referred to as wt %) of Cr is well known. This stainless steel can be produced at low production cost and exhibits excellent corrosion resistance against carbon dioxide gas. However, it is sensitive to sulfide stress corrosion cracking and thus is unsuitable for use in sulfide environments.
Recently, tubular goods of 13% Cr steel containing Mo, Ni and the like have been developed as disclosed in, for example, Japanese Unexamined Patent Publication No. 60-174,859 in order to adapt to environments containing small amounts of hydrogen sulfide. These tubular goods exhibit excellent resistance to sulfide stress corrosion cracking (SSC resistance).
On the other hand, the API Standard defines 12% Cr martensitic stainless steel containing reduced carbon as a line pipe material. However, this stainless steel requires preheating and postheating during circumferential welding, resulting in increased cost and toughness deterioration of the weld section. Thus it is little used.
Because 13% Cr steel containing Ni and Mo does not take into consideration weldability, weld cracks will surely occur when welding line pipes made of such a steel without preheating and postheating.
Accordingly, dual-phase stainless steel, which exhibits excellent weldability and corrosion resistance, has been used in line pipe materials. However, dual-phase stainless steel has unnecessary high cost for some oil and natural gas wells, causing increased well construction costs.
When hot oil or gas flows in a line pipe, the strength of the line pipe decreases. Thus, various corrective measures have been taken, for example, increasing room temperature strength of the line pipe, and increasing pipe thickness. However, increasing room temperature strength has been found to deteriorate weldability, and increasing the pipe thickness of course increases material and production costs.
In summary, no conventional line pipe material exhibits adequately stable corrosion resistance, satisfactory toughness of the weld heat-affected zone, and satisfactory high temperature strength. Further, all the known materials have serious cost disadvantages.

Martensitic steel for line pipe having excellent corrosion resistance and weldability


A method simultaneously aligns the two sets of optical wireless link transceiver mirrors such that light traverses a path from the transmitting laser off an outbound mirror, through free space, off the inbound mirror of the remote station, and finally onto the receiving element in the remote station.

1. Field of the Invention
This invention relates generally to optical wireless communication links, and more particularly, to a method of aligning optical wireless transceivers having distinct mirrors for transmitting and receiving.
2. Description of the Prior Art
FIG. 1 illustrates an optical wireless link (OWL) system 100 consisting of two stations 102, 104, in which each station 102, 104 contains an optical transmitter 106, 114 and an optical receiver 108, 116 respectively. FIG. 2 illustrates the optical components associated with a single OWL transceiver 102. Transceiver 102 can be seen to include a laser transmitter 106 and a MEMs mirror 120 for directing a transmitted beam toward a remote station 104. Although existing OWL devices are not equipped with a MEMS mirror for directing an incident beam to a receiving element, transceiver 102 also has a receiver 108 and a MEMs mirror 122 for directing an incident beam to a receiving element 121 (likely through optional magnifying optics 123) in the transceiver 102.
FIG. 3 shows an OWL receiver and an OWL transmitter including the respective field of view 124 and beam divergence 126. Looking again at FIG. 2 and considering an existing OWL device, mirror 120 directs the transmitted beam toward the remote receiver 116, which must be oriented such that its field 124 of view includes the transmitting mirror 120 in order to receive the transmitted beam. One of the limiting factors associated with modern optical wireless transceivers results from the constraint on the receiver that it have a wide field of view 124 in order to see the incident beam across a relatively large angle. A receiver with a narrow field of view 124 would allow optics to intensify the incident beam, significantly increasing the SNR and subsequently the operating range of the system 100. A narrow field of view however, requires either very accurate positioning of the transceivers 102, 104 (such that the incident laser beam falls within the field of view of the respective receivers 108, 116). Otherwise, some method of re-directing the incident beam to compensate for initial positioning error will be required. A mirror, such as 122 in FIG. 2, can be used to re-direct the beam allowing the desired narrow field of view; however, it must be positioned in the proper orientation in order for the system to function.
In view of the foregoing, it would be desirable and advantageous in the optical wireless communication art to provide a technique for simultaneously aligning the two sets of mirrors (local transmitting mirror and remote receiving mirror) such that light traverses a path from the transmitting laser 106 of the outbound mirror 120, through free space, off the inbound mirror of the remote station 104, and finally onto the receiving element in the remote station.

Method of aligning optical wireless transceivers comprising distinct mirrors for transmitting and receiving


A phosphorous-containing zeolite with structural type CON in its aluminosilicate or borosilicate form contains at most 10% by weight of phosphorous. A process for its preparation is described, starting from existing zeolites (SSZ-26, SSZ-33 or CIT-1) or from beta zeolites and an organic structuring agent or template which is 1-N,N,N-trimethyl adamantammonium hydroxide or 2-N,N,N-trimethyl adamantammonium hydroxide. The zeolite is used for catalytic cracking of hydrocarbon feeds.

The present invention relates to a novel large pore multi-dimensional phosphorous-containing zeolite with structural type CON, its preparation and its use, in particular in a process for catalytic cracking of a hydrocarbon feed. More precisely, it relates to a borosilicate molecular sieve which can be transformed into an aluminosilicate and stabilized by at least one phosphorous-containing compound.
Zeolitic molecular sieves are crystalline materials comprising a network of three-dimensional TO.sub.4 tetrahedra where T is Si, Al, B, P, Ge, Ti, Ga, Fe, for example. This network defines a microporous intracrystalline network with dimensions which are comparable to those of small to medium organic molecules. The microporous network can be a system of channels and/or cavities, shaped by the crystalline network, and which can be identified by its particular and specific X ray diffraction diagram.
The potential applications of a zeolite (for example in catalysis, adsorption, cation exchange and purification processes) depend principally on the size, shape and characteristics (uni-, multi-dimensional) of their microporous network and their chemical composition. As an example, in aluminosilicate type zeolites, the presence of AlO.sub.4.sup.- tetrahedra isolated in a matrix of SiO.sub.4 tetrahedra requires the presence of compensation cations to counter-balance the negative charge of the framework. These cations are typically highly mobile and can be exchanged with others, for example H.sup.+ or NH.sub.4.sup.+, the latter being able to be transformed into H.sup.+ by calcining, resulting in an acidic microporous solid. The zeolite is then in its acid form also known as its hydrogen form. When all of the compensating cations are organic alkylammonium or ammonium cations, calcining leads directly to the acid form of the zeolite. Such microporous acidic solids can be used in acid catalysis processes and their activity and selectivity depend on the strength of the acid, on the size and the on dimensional characteristics of the space delimited in the framework, in which the acidic sites are found.
The channel size can be described by the number of TO.sub.4 tetrahedra present in the ring delimiting the pore openings, which element controls the diffusion of molecules. Thus the channels are classified into categories: small pore openings (annular pore openings delimited by a sequence 8 TO.sub.4 tetrahedra (8 MR, medium pores (10 MR) and large pores (12 MR), MR standing for membered ring.
The prior art is illustrated in U.S. Pat. No. 5,110,776, International patent application WO-A-9507859 and the publication by S. I. Zones et al., "Boron-beta zeolite hydrothermal conversions: The influence of template structure and boron concentration and source", Microporous Material, Elsevier, vol. 2, 1994, Amsterdam, NL, pages 543-555.
Of the numerous zeolites which have already been described in the literature, zeolites with structural type CON, i.e., SSZ26 zeolite (PCT/US 89/01179, 1989), SSZ-33 zeolite U.S. Pat. No. 4,963,337) and CIT-1 zeolite (J. Am. Chem. Soc., 1995, 117, 3766) are of interest as they are the only synthetic zeolites known to possess an interconnected medium (10 MR) and large (12MR) pore system.
This structural characteristic can result in interesting form selectivity properties in such materials for heterogeneous catalysis. The term "form selectivity" is generally used to explain specific catalytic selectivities due to steric constraints which exists inside the microporous zeolitic system. Such constraints can affect the reactants (diffusion of reactants in the zeolite), the reaction products (formation and diffusion of the formed products from the zeolite), the reaction intermediates or the reactional transition states which form in the micropores of the zeolite during the reactions. The presence of appropriate steric constraints can in some cases prevent the formation of reaction intermediates and transition states leading to the formation of unwanted products and can in some cases improve selectivities.
The family of 10/12 MR zeolites consists of intergrowths of two polymorphs in different proportions. The differences between the SSZ-26, SSZ-33 and CIT-1 zeolites originate from the preparation method, chemical composition (zeolites/as synthesized) and the relative proportion of polymorphs in the intergrowth. Thus CIT-1 and SSZ-33 zeolites each belong to the category of as synthesized borosilicate materials. The term "as synthesised" means any zeolite obtained directly from its preparation with no intermediate modification. CIT-1 zeolite is substantially constituted by a single polymorph, while SSZ-33 is an intergrowth. SSZ-26 zeolite is an alumino-silicate constituted by an intergrowth.
The silica-alumina composition of the three structures appears to be similar. However, their preparation (that of SSZ-26 and CIT-1) requires expensive structuring agents (templates) and lengthy synthesis processes. Thus SSZ-26 zeolite has been described in U.S. Pat. No. 4,910,006 and U.S. Pat. No. 4,963,337 describes SSZ-33 borosilicate, in its aluminium form, hereby incorporated by reference.
Such zeolites are synthesised in the presence of alkaline ions supplied by sodium hydroxide. These ions must be eliminated by at least one ion exchange step, for example using ammonium cations, and a calcining step, which complicates the preparation process and renders it more expensive.

Phosphorous-containing zeolite with structural type CON, its preparation and its use for catalytic cracking


A dielectric layer and a method of forming thereof. An opening defined in a dielectric layer and a wire deposited within the opening, wherein the wire includes a core material surrounded by a jacket material, wherein the jacket material exhibits a first resistivity ρ1 and the core material exhibits a second resistivity ρ2 and ρ2 is less than ρ1.

As integrated circuit features are scaled down and density increases, material properties such as resistivity, which influences observed resistance, exhibit relatively more pronounced effects. For example, as feature size drops, interconnect delay may exceed gate delay and form a relatively large portion of total device delay. Interconnect delay is understood to be caused, at least in part, by resistive-capacitance delay. Resistive-capacitance delay, or RC delay, is understood as the delay of signal propagation as a function of resistance, which is in part dependent on the resistivity of the metal wire composition, and as a function of insulator capacitance, which is in part dependent on the permittivity of the interlayer dielectric. Prior solutions to reduce RC delay included wire geometry optimization.
Furthermore, reliability of integrated circuits is affected by a number of stresses that increase as feature size drops and density increases. These stresses include electrical, thermal, mechanical and environmental stress. Electromigration is an example of phenomena that reduces semiconductor reliability, leads to interconnect failure, and becomes relatively more prominent as feature size is decreased and power density increases. Electromigration is understood as the transport of material due to movement of ions in a conductor. Electromigration may result in the formation of hillocks or voids in the interconnects and eventually lead to failure.
To reduce electromigration, and other stress induced failures, refractory metals have been used in interconnect fabrication. However, refractory metals exhibit increased resistivity and, therefore, increased resistance, increasing resistive-capacitance delay. To further reduce electromigration, and other stress induced failures, diffusion barriers have been deposited on the side and bottom walls of openings in interlayer dielectrics containing the interconnects. Diffusion barriers are understood to occupy a small fraction (typically 20% or less) of the cross-sectional area of the interconnect wire. The portion of the interconnect exposed at the surface of a given dielectric layer is coated with an insulator such as silicon nitride. However, such an arrangement may adversely affect wire properties such as capacitance.
Therefore, as feature sizes continue to decrease, room remains for the improvement in the design of interconnects with, in some instances, an emphasis on interconnect delay and resistance to various stresses, such as those resulting in electromigration and thermomechanical failures.

Interconnect wires including relatively low resistivity cores


Mechanisms for automatically generating code that tests capabilities of a test computing system to simulate a message exchange pattern. The code generation computing system uses a message exchange pattern definition to generate the simulation code. For each state in which the message exchange pattern definition allows valid messages to be transmitted, code is generated for that state that at least simulates the transmission of a valid transmission message. For each state in which the message exchange pattern definition allows valid messages to be received, code is generated for that state that simulates the receipt of a valid receipt message. If the transmission or receipt of the message causes a state transition to occur, code is generated that causes the appropriate state transition in the message exchange pattern.

1. The Field of the Invention
The present invention relates to networking technologies; and more specifically, to the automated generation of code that simulates a message exchange pattern.
2. Background and Related Art
Computing technology has transformed the way we work and play. Computing systems now take a wide variety of forms including desktop computers, laptop computers, tablet PCs, Personal Digital Assistants (PDAs), and the like. Even household devices (such as refrigerators, ovens, sewing machines, security systems, and the like) have varying levels of processing capability and thus may be considered computing systems.
Much of the functionality provided by computing systems relies on the computing system being networked with (and able to communicate messages with) other computing systems. In order for the two communicating computing systems to accomplish a particular task, a message transaction involving a pattern of message exchanges may be needed. Each computing system involved in the message transaction has an application (hereinafter also referred to as a "message exchange pattern application") that assists in processing messages received as part of the transaction that follows the message exchange pattern, and transmitting other messages that conform with the message exchange pattern.
In order to test a message exchange pattern application, the message exchange pattern application may be installed on different computing systems and then tested. However, in many cases, the message exchange pattern application on one computing system may be significantly different than the message exchange pattern application on another computing system, even though the two message exchange pattern applications are capable of interacting with each other using the message exchange pattern. The tester might only have access to one of the message exchange pattern applications. Furthermore, the owner of the other message exchange pattern application may not be willing or able to cooperatively test the interaction of the two message exchange pattern applications. Accordingly, it is not always feasible to test the message exchange pattern application in an actual network environment in which it will be implemented and deployed.
What would be advantageous is a mechanism for testing message exchange pattern applications without having to test the application in the actual network environment in which it would ultimately be employed. It would furthermore be advantageous if this testing may be accomplished without requiring the authoring of additional testing software each time a message exchange pattern application is to be tested.

Automated generation of message exchange pattern simulation code


An apparatus includes an intra-body probe and a processor. The intra-body probe includes an electrode, which is configured to contact tissue in a heart. The processor is configured to receive an electrical signal from the electrode, to distinguish a local component, due to the tissue with which the electrode is in contact, in the electrical signal from a remote-field contribution to the signal, and to control a therapeutic procedure applied to the tissue responsively to the distinguished local component.

Various techniques are known in the art for cardiac ablation therapy. U.S. Patent Publication No. 2010/0331658, whose disclosure is incorporated herein by reference, describes an open-irrigated catheter system comprising a tip section, a distal insert, and mapping electrodes. The tip section has an exterior wall that defines an open interior region within the tip section. The exterior wall includes mapping electrode openings and irrigation ports. The exterior wall is conductive for delivering radio frequency (RF) energy for an RF ablation procedure. The irrigation ports are in fluid communication with the open interior region to allow fluid to flow from the open interior region through the irrigation ports. The distal insert is positioned within the tip section to separate the open region into a distal fluid reservoir and a proximal fluid reservoir. The mapping electrodes are positioned in the mapping electrode openings in the tip section.
U.S. Patent Publication No. 2007/0006254, whose disclosure is incorporated herein by reference, describes a method of controlling a remote navigation system that orients the distal end of a medical device in response to user inputs, including interrupting the operation of the remote navigation system when the user inputs would navigate the medical device to a location where the impedance exceeds a predetermined value. A method of controlling ablation of cardiac tissue to block an errant signal causing an arrhythmia includes ablating tissue until there is a predetermined reduction in the amplitude of the errant signal or a predetermined reduction in local impedance.
U.S. Pat. No. 7,959,630, whose disclosure is incorporated herein by reference, describes assemblies, probes, and methods for creating circumferential lesions in tissue, e.g., the tissue within or around the ostium of a vessel. An ablation probe with an ablative structure can be placed in contact within or around the ostium of the vessel. A diagnostic probe can be introduced through a lumen within the ablation probe and inserted into the vessel. Energy can be provided to the ablative structure to create a circumferential lesion within or around the ostium of the vessel, and the diagnostic structure can be used to diagnose the tissue to determine whether the circumferential lesion can be properly created.
U.S. Patent Publication No. 2006/0253115, whose disclosure is incorporated herein by reference, describes catheters, systems, and methods which are provided for performing medical procedures, such as tissue ablation, adjacent the ostia of anatomical vessels, such as pulmonary veins. A catheter comprises an elongated flexible catheter body including a proximal shaft portion and a distal shaft portion, which has a proximal section pre-shaped to form a curve having an apex sized to be inserted into an anatomical vessel, such as a pulmonary vein, and a distal section configured to contact an ostium of the vessel when the curve apex is inserted within the vessel ostium. The catheter further comprises a steering mechanism configured for decreasing a radius of curvature of the curve.

Real time assessment of ablation from electrocardiogram signals


A battery management system includes multiple sensors, status detection circuitry, and fault detection circuitry. The sensors sense statuses of a battery pack. The status detection circuitry detects whether the battery pack is in a normal condition based on the statuses to generate a detection result. The fault detection circuitry detects whether a fault is present in the battery pack. The sensors include a current sensor that senses a battery current of the battery pack. The fault detection circuitry includes a detection circuit that monitors a rate of change of a voltage at a terminal of the battery pack, and detects whether a fault is present in the current sensor based on a result of a comparison between the rate of change and a threshold and based on the detection result.

FIG. 1 illustrates a circuit diagram of a conventional battery pack 100. The battery pack 100 includes battery cells 102, a battery management system (hereinafter, BMS) 104, and sensors such as a sense resistor RSEN and a thermistor RTHM. The sense resistor RSEN generates a sense voltage VSEN indicative of a current flowing through the battery cells 102. The thermistor RTHM generates an indication voltage VTHM indicative of the temperature in the battery pack 100. The BMS 104 protects the battery pack 100 from, e.g., an over-current condition, an over-temperature condition, an under-temperature condition, etc., based on the sensed information, e.g., VSEN and VTHM, from the sensors. However, if the sensors and the BMS 104 are not well connected or if the sensors are broken, then the BMS 104 cannot receive correct information from the sensors, and this may place the battery pack 100 and/or a system load powered by the battery pack 100 at a high risk of being damaged.
Additionally, the BMS 104 includes a voltage regulator (not shown) that generates a regulated output to power internal function blocks and/or peripherals such as a microcontroller unit (MCU), an LED (light-emitting diode) display, LDO (low dropout) regulator, etc. If a fault (e.g., a short circuit) is present in the components powered by the voltage regulator, it can draw excessive current from the voltage regulator and generate heat to damage the BMS 104 and/or the battery pack 100.

Fault detection for battery management systems


The invention provides a technique for assigning a server to manage resources. The server identifies a capacity value that represents a maximum number of resources that the server can simultaneously manage, and parses data included in a tracker directory to identify the resources that have the fewest number of servers assigned to manage them. Next, based on the capacity value, the server registers to manage the identified resources, where each registration to manage an identified resource results in the server actively managing the resource when no other server is registered to manage the resource, or acting as a backup manager to the resource when at least one other server is registered to manage the resource, and the tracker directory is updated accordingly. Finally, the server, for each registration that results in actively managing a resource, configures itself to process client device requests that are directed to utilizing the resource.

The proliferation of client computing devices—such as smart phones and tablets—has drastically changed the manner in which software applications are designed and executed. Some software applications—such as games—are designed to run independently on client computing devices and require little or no interaction with a server. Other software applications—such as photo sharing applications—rely on accessing server computing devices that are designed to interact with the software applications. Notably, implementing and managing such server computer devices can be complicated and expensive, and often exceeds the resources that are available to the average developer. To address this problem, "cloud computing" services were created, which provide scalable computing resources that remove the necessity for a developer to implement his or her own server computing devices.
Notably, existing approaches used to implement and manage cloud computing services are quite complex and require considerable overhead, especially when seeking to meet customer demands for both high availability and high scalability. First, high availability represents a system design approach that guarantees that a particular portion of servers and databases (e.g., 75%) are always functioning properly and online. This typically requires system administrators to be physically onsite to swap out ill-functioning hardware, which is expensive and susceptible to shortcomings and human error. Next, high scalability represents a system design approach that enables the number of servers and databases to dynamically increase or decrease in number. This typically involves system administrators upgrading hardware and updating a configuration that defines the hierarchy and structure of the system—which, similar to the high-availability issues described above—is susceptible to shortcomings and human error.


Provided are a crystalline dihydrate of Rivaroxaban, processes for the preparation thereof, pharmaceutical compositions containing the crystalline dihydrate and processes for preparing and storing the pharmaceutical compositions. Also provided are a crystalline formic acid solvate of Rivaroxaban, processes for the preparation of crystalline Rivaroxaban formic acid solvate and the use of the Rivaroxaban formic acid solvate in the manufacture of the crystalline dihydrate of Rivaroxaban.

Rivaroxaban, 5-Chloro-N-({(5S)-2-oxo-3-[4-(3-oxomorpholin-4-yl]phenyl)-1,3-oxazolidin-5-yl}methyl)thiophene-2-carboxamide, also known as BAY 59-7939 and marketed under the trade name Xarelto®, is a direct factor Xa Inhibitor and as such an antithrombotic agent having the formula:
(see also J. Med. Chem. 2005, 48, 5900-5908).
Rivaroxaban exists in several polymorphic forms, which have been called "modification I", "modification II" and "modification III" in WO 2007/039132. The same document also mentions a hydrate, an NMP solvate, a THF-clathrate and an amorphous form of Rivaroxaban. WO 2007/039132 describes that modification II and the amorphous form are to be preferably used in finished dosage forms due to their higher solubility in comparison to modification I. Modification II is described to have a 4-fold higher solubility compared to modification I.
Form I of Rivaroxabin is reported to be of a relatively low solubility, see e.g. the CHMP assessment report Procedure No. EMEA/H/C/000944, and WO2005/060940 mentions that difficulties in oral bioavailability of Rivaroxaban had allegedly to be overcome during the development of an oral dosage form based on modification I. WO2007/039122 mentions as an alternative that melt extrusion and the use of amorphous Rivaroxaban prepared by melting can be of help in improving the oral bioavailability of Rivaroxaban.
It is interesting to note that the preferred, since more soluble, modification II of Rivaroxaban is not employed in the presently marketed oral dosage forms of Rivaroxaban (see e.g. the CHMP assessment report Procedure No. EMEA/H/C/000944), but the less soluble modification I. One possible explanation might be that modification II of Rivaroxaban can not be easily prepared following the processes disclosed in WO2007/039132, in particular when production of modification II, in particular polymorphically pure modification II, is attempted on commercial scale. In WO2007/039132 modification II is prepared by allowing a solution of Rivaroxaban in 1,4-Dioxan to evaporate at 50° C. or by shock-cooling. These process are not easily carried out on large scale at low cost.
There remains thus a need for a novel polymorph of Rivaroxaban with improved solubility properties compared to the sparsely soluble modification I of Rivaroxaban, which polymorphic form at the same time lends itself to facile production at commercial scale, contrary to modification II, preferably at low cost.
Moreover, different crystal forms of one compound may interconvert, that is under certain conditions one crystal form with favorable characteristics may convert to another crystal form with possibly less favorable characteristics. There is thus a need for pharmaceutical compositions comprising rivaroxaban in that very defined polymorphic state which shows favorable characteristics.

Crystalline form of rivaroxaban dihydrate


Disclosed is a vibration isolation apparatus for a wine refrigerator including a main body having a storage chamber and a mounting space, a base plate disposed at the mounting space of the main body with a predetermined interval from the main body, for forming the mechanical chamber with the mounting space, a compressor being installed on the top surface of the base plate, and an interval maintaining elastic support means coupled between the main body and the base plate, for maintaining a predetermined interval between the main body and the base plate, and elastically supporting the base plate. The vibration isolation apparatus for the wine refrigerator can store wines without deteriorating the special taste of the wines, by preventing the wine bottles stored in the wine refrigerator from being shaken in the operation of the wine refrigerator.

1. Field of the Invention
The present invention relates to a wine refrigerator, and more particularly to, a vibration isolation apparatus for a wine refrigerator which can prevent wine bottles stored in the wine refrigerator from being shaken in the operation of the wine refrigerator.
2. Description of the Background Art
In general, a refrigeration cycle system is mounted inside a refrigerator. An evaporator composing the refrigeration cycle system generates cool air. The cool air is circulated inside the refrigerator, for cooling the refrigerator.
Refrigerators can be classified into various shapes according to structural properties. Also, various types of refrigerators have been developed according to kinds of stored foods.
Recently, a cosmetics refrigerator and a wine refrigerator for storing cosmetics and wines in an optimum state have been developed.
Similarly to the general refrigerator, the wine refrigerator includes a main body having a storage chamber for storing wines, and a door mounted on one side of the main body, for opening or closing the storage chamber.
A refrigeration cycle system is formed in the main body. A compressor and a condenser of the refrigeration cycle system that generate vibration noise and heat are mounted on a mechanical chamber disposed at the lower portion of the main body.
FIG. 1 is a perspective view illustrating disassembly of the mechanical chamber of the conventional wine refrigerator, and FIG. 2 is a front-sectional view illustrating the mechanical chamber of the conventional wine refrigerator.
Referring to FIGS. 1 and 2, in the mechanical chamber, a predetermined size of mounting space R is formed at a bottom rear portion of a main body 100, a predetermined area of bottom plate 110 is fastened to the bottom surface of the main body 100 by using a plurality of screws, and a cover 200 for covering the rear portion of the mounting space R is coupled to the bottom rear surface of the main body 100 by using a plurality of screws 210. The bottom plate 110 covers the bottom surface of the mounting space R of the main body 100.
A compressor 300 is installed on the bottom plate 110 to be positioned inside the mechanical chamber, a control box 400 is mounted on the sidewall of the mechanical chamber, and a defrosted waterspout 500 is installed on the inside top surface of the mechanical chamber to be positioned over the compressor 300. Water generated by frost molten in an evaporator (not shown) is collected in the defrosted waterspout 500 and evaporated.
The compressor 300 includes an airtight vessel 310, and a plurality of mounting plates 320 coupled to the bottom surface of the airtight vessel 310. A suction pipe 330 and a discharge pipe 340 for sucking and discharging refrigerants are connected respectively to the airtight vessel 310. The suction pipe 330 is connected to the evaporator, and the discharge pipe 340 is connected to a condenser (not shown) composing the refrigeration cycle system.
The structure of installing the compressor 300 on the bottom plate 110 will now be explained.
Through holes 321 are formed on the mounting plates 320 of the compressor 300, and through holes 111 corresponding to the through holes 321 of the mounting plates 320 are formed on the bottom plate 110. Cylindrical rubber vibration isolators 360 having a predetermined length are positioned between the bottom plate 110 and the mounting plates 320. Fixing bolts 370 are inserted into the through holes 111 of the bottom plate 110, the rubber vibration isolators 360 and the through holes 321 of the mounting plates 320, and nuts 380 are fastened to the fixing bolts 370. Accordingly, the mounting plates 320 and the rubber vibration isolators 360 are fixedly coupled to the bottom plate 110.
Two front legs 120 for supporting the main body 100 are coupled to the front edges of the bottom plate 110 mounted on the bottom surface of the main body 100, and two rear legs 130 for supporting the main body 100 are coupled to the rear portion of the bottom plate 110 at predetermined intervals. The front legs 120 can control height, and the rear legs 130 that are rollers can easily transport the refrigerator. The front legs 120 and the rear legs 130 contact the bottom surface on which the refrigerator is put, for supporting the refrigerator.
Reference numerals 350 and 220 denote a dryer and air vent holes, respectively.
In the operation of the refrigerator, when the compressor 300 sucks, compresses and discharges refrigerants, vibration noise and heat are generated. The heat generated by the compressor 300 is emitted through the air vent holes 220 of the cover 200. The vibration generated by the compressor 300 is slightly absorbed by the rubber vibration isolators 360. However, since the rubber vibration isolators 360 are disposed to directly contact the mounting plates 320 of the compressor 300 and the bottom plate 110, the vibration is transmitted to the bottom plate 110 through the rubber vibration isolators 360. Because the bottom plate 110 is coupled to the main body 100 through the plurality of screws, the vibration transmitted to the bottom plate 110 is directly transmitted to the main body 100. As a result, the bottom plate 110 and the main body 100 are vibrated, to cause vibration noise.
In general, wines are ripen in wine bottles. To preserve the special taste of the wines, the wines must be carefully handled and stored. Especially, temperature, sunlight, humidity, vibration and horizontality must be taken into consideration to handle and store wine bottles.
In the development procedure of the wine refrigerator, it is quite easy to control sunlight, humidity and horizontality but difficult to maintain an optimum temperature of the wine bottles and intercept vibration. Thus, researches have still been made on it.
In the case of the wine refrigerator described above, since the vibration generated by the mechanical chamber is transmitted to the main body 100, the wine bottles stored in the storage chamber of the main body 100 are more or less shaken. Accordingly, the special taste of the wines is deteriorated.

Vibration isolation apparatus for wine refrigerator