A process for assaying for cancer of the prostate, comprising assaying a sample derived from a human for prostate specific antigen having a linked oligosaccharide which is at least triantennary. The assay may employ a binding molecule which binds to oligosaccharides that are at least triantennary, but does not bind to oligosaccharides that are monoantennary or diantennary. Such binding molecule may be a lectin such as PHA-L or an antibody to an oligosaccharide that is at least triantennary.

Despite the widely accepted use of PSA as a marker for prostate cancer, this molecule has not yet been completely characterized. Past studies have established, however, using both amino acid and cDNA sequencing techniques, that PSA contains 237 amino acids, with a molecular mass of 26,079 Da for the peptide moiety of the molecule. The predominant PSA molecular species detected by ion spray mass spectrometry (ISMS) was at relative molecular mass of 28,430, indicating that PSA contains a carbohydrate residue having a molecular weight of 2,351 for a total weight percentage of carbohydrate of 8.3% (Belanger, A., et al., Prostate, 27:187-197 (1995)). PSA is a kallikrein-like serine protease that is produced exclusively by the epithelial cells of all types of prostatic tissue, benign and malignant. Physiologically, it is present in the seminal fluid at high concentration and functions to cleave the high-molecular weight protein responsible for the seminal coagulum into smaller polypeptides. (Oesterling, J. E., J. Cell Biochem. Suppl., 16H:31-43 (1992).)
Prostate-specific antigen was first described by Wang, M. C., et al., Invest. Urol., 17:159 (1979). It is a secretion of prostate epithelium and is also produced by prostate cancer cells. PSA was characterized as a glycoprotein monomer with protease activity. More recently, the amino acid sequence of the antigen has been reported (Watt, W. K., et al., PNAS USA, 83:3166 (1986)) and the gene for PSA has been cloned (Lundwall, A., Biochem. Biophys. Res. Commun., 161:1151 (1989)).
A variety of carbohydrate markers have been used to reveal the importance of carbohydrate information in the clinical characteristics of human carcinomas. Consequently, carbohydrate profiles of the primary tumor have been correlated with tumor grade, metastatic potential and prognosis, which are not mutually unrelated. Oncogenesis is usually associated with alterations in cell surface carbohydrate structure, and tumor-associated carbohydrate markers have been utilized in the diagnosis and followup of human cancers. (Hakomori, S., Adv. Cancer Res., 52:257-331 (1989).) Recently, it has been shown that carbohydrate structures on the tumor cell surface are associated with the metastatic potential of tumor cells.
The association of carbohydrate signals with metastatic potential was first revealed in experimental systems. Notably, .beta.1.fwdarw.6 branching of asparagine-linked oligosaccharides, which are increased in a number of tumor cells (Yamashita, K., et al., J. Biol. Chem., 259:10834-10840 (1984), and in metastases of murine melanomas and fibrosarcomas (Dennis, J. W., et al., Science, 236:582-585 (1987)). N-linked glycosylation is initiated in mammalian cells, as in those of all higher eukaryotes, with the transfer of the precursor oligosaccharide to accepted asparagine residues of nascent or newly synthesized proteins. Subsequent modification of this oligosaccharide generates the extreme diversity of N-linked oligosaccharides found in mature glycoproteins. Steric accessibility to Golgi enzymes appears to determine whether the processing of a given N-linked glycan stops at the oligomannose stage or proceeds further (Hsieh, P., et al., J. Biol. Chem., 258:2555-2561 (1983)). However, the regulation of the later stages of processing, in which a wide variety of bi, tri, and tetraantennary complex glycans are synthesized, is only poorly understood. This regulation is of special interest because it is altered in many differentiating (Feizi, T., Nature, 314:53-57 (1985)) or oncogenically transformed (Warren, L., et al., Biochem. Biophys. Acta., 516:97-127 (1978)) cells, resulting in a shift in an N-linked oligosaccharide composition. This is likely to have physiologically significant consequences, since altered protein glycosylation can affect processes such as adhesion, metastasis and immune recognition. (Hubbard, S. C., Journal of Biological Chemistry, 262 (34):16403-16411 (1987).)
The proposed carbohydrate structure of PSA is a diantennary N-linked oligosaccharide of the N-acetyllactosamine type, with a sialic acid group at the end of each of the two branches. Approximately 70% of the PSA molecules contain a fucose group in the core chitobiose moiety. PSA contains only one N-linked chain, which is linked to asparagine.sup.45 (Watt, et al., Proc. Nat. Acad. Sci., Vol. 83, pgs. 3166-3170 (1986); Schaller, et al., Eur. J. Biochem., Vol. 170, pgs. 111-120 (1987); Riegman, et al., Biochem. Biophys. Res. Commun., Vol. 155, pgs. 181-188 (1988); Van Halbeek, Methods in Molecular Biology, Jones, et al., eds., Totowa, N. J., Humana Press, pgs. 115-148 (1993); Lundwall, et al., FEBS Lett., Vol. 214, pgs. 317-322 (1987)). Van Halbeek, et al. suggest that this protein is composed of several isoforms whose structure may differ in their carbohydrate composition.
The proposed carbohydrate structure of PSA confirms that only one glycosylation site in the protein is occupied. This glycosylation site is readily identified based on the amino acid sequence of the protein; the only consensus ASN-X-SER/THR sequence in PSA is found at residue 45-46-47 (ASN-LYS-SER). (Belanger, et al.). The complete characterization in the structure of the carbohydrate side-chain of PSA has been determined by Belanger, et al.
Carcinoma of the prostate has long been regarded as an unpredictable disorder which makes sound therapeutic decisions in evaluating the results of different types of treatment very difficult. Prostate cancer is unique among the potentially lethal human malignancies in that there is a wide discrepancy between the high prevalence of histologic changes recognizable as cancer and the much lower prevalence of clinical disease.
The concept that adenocarcinoma of the prostate exists in a latent and a clinical form is supported by epidemiologic, pathologic and clinical evidence. Although these divergent manifestations of prostate cancer have come in architectural and cytologic features, they can be distinguished from each other to some degree by differences in certain pathologic features, such as the volume, grade, and invasiveness of the lesion.
Prostate cancer has become the most common cancer among American men, and only lung cancer is responsible for more cancer deaths (Boring, C. C., Cancer Statistics, 41:19-36 (1991)). The age specific mortality rate has slowly increased over the past 50 years and in black American men is nearly double the rate found in white men (Carter, H. B., Prostate, 16:39-48 (1990)). Prostate cancer is responsible for nearly three percent of all deaths in men over the age of 55 years (Seidman, H., et al., Probabilities of Eventually Developing or Dying of Cancer-United States, 35:36-56 (1985)). Since the incidence of prostate cancer increases more rapidly with age than any other cancer, and the average age of American men is rising, the number of patients with prostate cancer is expected to increase dramatically over the next decade.
Approximately 30% of men with prostate cancer have distant metastases at the time of diagnosis (Schmidt, J. D., et al., J. Urol., 136:416-421 (1986)). Despite the impressive symptomatic response of metastases to hormonal manipulation (androgen deprivation), the survival rate for these patients is dismal: the median duration of survival is less than three years (Eyar, D. P., Urologic Pathology: The Prostate, Philadelphia, Pa., Lea and Febiger, 241-267 (1977)). By five years, over 75% and by ten years, more than 90% of these patients die of their cancer rather than with it (Silverberg, E., Cancer, 60:692-717 (1987) (Suppl.)). The problem with prostate cancer is that many forms of prostate cancer are latent, in other words, such forms are difficult to detect. Approximately 30% of the men over the age of 50 years who have no clinical evidence of prostate cancer harbor foci of cancer within the prostate (McNeal, J. E., et al., The Lancet, January, 11:60-63 (1986)). This remarkably high prevalence of prostate cancer at autopsy, seen in no other organ, makes it the most common malignancy in human beings (Dhom, G., J. Cancer Res. Clin. Oncol., 106:210-218 (1983)) . There is strong support for the concept of multi-step process in the pathogenesis of prostate cancer in which latent cancers progress through some but not all of the steps necessary for full malignant expression (Utter, H. B., et al., J. Urol., 143:742-746 (1990).
There are a variety of techniques for early detection and characteristics of prostate cancers, however, none of them are devoid of any problems. Prostate cancer is a notoriously silent disease with few early symptoms. Symptoms associated with bladder outlet obstruction are commonly present in men over the age of 50 years and are often ascribed to benign prostatic hyperplasia (BPH).
Digital rectal examination (DRE) traditionally has been considered the most accurate test for the detection of prostate cancer. DRE has been demonstrated to be more sensitive, more specific, and to have a greater efficiency than a variety of laboratory tests available, however, few of these laboratory tests are still in clinical use today (Guinan, P., et al., N. Engl. J. Med., 303:499-503 (1980)). DRE detects cancer relatively late, and there is only a weak correlation between the size of the cancer estimated by DRE and the actual volume of cancer present. The most serious limitation of DRE is its lack of sensitivity (false-negative results). For example, approximately 10% to 20% of transurethral resections performed for benign prostatic hypertrophy in patients with no palpable abnormalities suggestive of cancer uncover an incidental cancer of the prostate. DRE detected only 12 of 22 cancers found in a screening study, while transrectal ultrasonography (TRUS) found 20 (Lee, F., et al., Radiology, 168:389-394 (1988)). Thus, DRE is relatively insensitive and nonspecific. Cancers detected by palpation are relatively large, late in their development and no longer curable, and some are very small, such that they are clinically unimportant cancers.
Patients having prostate cancer have an elevated prostate-specific antigen level. Cancer was detected in 26% of the men with a PSA level of 4.0 to 10.0 ng/ml. Serum PSA levels have been shown to correlate generally with the volume, clinical stage, and pathologic stage of prostate cancer, although there is a wide range of PSA values associated with any given volume or stage (Hudson, M. A., J. Urol., 142:1011-1017 (1989)). PSA, however, is not predictive of the features of the cancer in the individual patient. If the level of PSA is greater than 10.0 ng/ml, 57% to 92% of the patients will have locally advanced cancer. Therefore, while more specific, using a PSA level higher than 10 ng/ml may not offer an effective technique for early detection. There are other theoretical limitations to the use of this serum marker for early detection. A normal serum PSA level does not exclude the diagnosis of cancer. False-negative results are common, and a third of men treated with radioprostatectomy for prostate cancer have a normal serum PSA level. False-positive results are also common since PSA levels are often elevated in men with common benign conditions, such as BPH or prostatitis. In summary, PSA levels have proved to be extremely useful in the early detection of prostate cancer, especially when combined with DRE or TRUS. A PSA level detection, however, must be used in combination with DRE or TRUS in order to be sure that what is present is cancer and not BPH or prostatitis.
The introduction of TRUS has provided physicians with an effective way to see the internal anatomy and pathology of the prostate gland. TRUS has been used to screen for prostate cancer in several large series and has consistently been shown to increase detection when compared with DRE. TRUS is performed by talking a sonograph of the pelvic area and perhaps the most important use of TRUS in the early detection of prostate cancer is as a guide for directed needle biopsies of the prostate (Lee, F., et al., Radiology, 170:609-615 (1989)).
PSA testing can have significant value in detecting metastatic or persistent disease in patients following surgical or medical treatment of prostate cancer (Lange, P. H., et al., Urology, 33 (6 Suppl.):13 (1989); and Killian, C. F., et al., Cancer Res., 45:886 (1985)). Persistent elevation of PSA following treatment or an increase in the post-treatment base-line PSA level is indicative of recurrent or residual disease (Brawer, M. K., et al., Urology, 33 (5 Suppl.):11 (1989)). Although PSA is prostate-specific, it is not prostate-cancer specific. As a result, benign conditions such as benign prostatic hyperplasia, prostatitis and infarction, as well as prostatic intraepithelial neoplasia, can be associated with elevated serum levels of PSA. (Osterling, J. E., J. Cell. Biochem. Suppl., 16H:31-43 (1992).)
Measurement of serum levels of PSA is widely used for diagnosis of prostate cancer and benign hypoplasia of prostate tissue. This serum marker is of value since it is derived only from the tissue of interest, but increased levels of PSA in serum do not allow a completely clear-cut diagnosis of benign versus malignant changes.
Accordingly, there is a need in the art to obtain an accurate diagnosis of prostate cancer through non-invasive techniques. There is also a clear need for diagnosing prostate cancer via detection of an altered form of PSA derived from a biological sample of the patient.
In accordance with an aspect of the present invention, there is provided a process for assaying for cancer associated with the presence of antigens having linked oligosaccharides which are at least triantennary, such as, for example, cancer of the prostate. The process comprises assaying a sample derived from a human for an antigen, such as, for example, prostatic-specific antigen or prostate specific antigen, having linked oligosaccharides which are at least triantennary.
The terms "prostatic-specific antigen" or "prostate specific antigen" (PSA), as used herein, mean a 237-residue protease with a molecular mass of approximately 26,079 daltons, or a derivative or analogue thereof, which is expressed nearly exclusively by human prostatic epithelial cells.
The term "antennary", as used herein, means the number of linkages of an N-linked oligosaccharide attached to an amino acid residue, such as, for example, Asp.sup.45, of PSA. The term "antennary" is preceded by the prefixes bi-, tri-, and tetra-, etc. These prefixes refer to the number of branches of the oligosaccharide.
Prostate cancers which may be detected in accordance with the present invention include metastatic prostate cancers and non-metastatic prostate cancers.
Although the scope of the present invention is not to be limited to any particular theoretical reasoning, applicants have found unexpectedly that, unlike normal PSA, which bears only biantennary oligosaccharide, PSA from prostate cancer has a mixture of biantennary and triantennary oligosaccharides. Such triantennary oligosaccharides, which are linked to an amino acid residue of PSA such as Asp 45, are associated with oncogenic transformation.
To determine the presence of the oligosaccharides which are at least triantennary, and which are N-linked to an amino acid residue, such as asparagine 45 of PSA, in one embodiment, prostatic-specific antigen is isolated from a biological sample derived from a patient. The biological sample includes, but is not limited to, serum, plasma, prostatic fluid, semen, urine, and spinal fluid. Subsequent to the isolation of PSA from the biological sample, the presence of N-linked oligosaccharides which are at least triantennary is determined.
Isolation of PSA may be performed by numerous methods which are well-known to those of the skill in the art. See Sambrook, et al., Molecular Cloning; A Laboratory Manual, 2nd ed., Cold Spring Harbor, New York, 1989, the disclosure of which is hereby incorporated by reference in its entirety.
For example, the PSA may be isolated and purified by methods including ammonium sulfate or ethanol precipitation, acid extraction, anion or cation exchange chromatography, phosphocellulose chromatography, hydrophobic interaction chromatography, affinity chromatography, and hydroxyapatite chromatography. Protein refolding steps can be used, as necessary, in completing configuration of the protein. Finally, high performance liquid chromatography can be employed for final purification steps.
In a preferred embodiment of the present invention, PSA is isolated through the use of an antibody, preferably bound to a solid support, which recognizes an epitope of PSA. The antibody may be polyclonal or monoclonal, preferably monoclonal.
The bound PSA then is contacted with a compound or binding molecule which binds to oligosaccharides which are at least triantennary. Such compound does not bind to oligosaccharides that are monoantennary or diantennary. Examples of compounds or binding molecules which bind to oligosaccharides which are at least triantennary , but do not bind to oligosaccharides which are monoantennary or diantennary, include, but are not limited to, the lectin PHA-L from red kidney bean (Phaseolus vulgaris), and antibodies which specifically bind to oligosaccharides which are at least triantennary. Such antibodies may be prepared by procedures known in the art. Such lectin also is available from Sigma labeled with biotin or cross-linked to beaded agarose. PHA-L also is described in Fu, et al., Anal. Biochem., Vol. 1, pgs. 53-63 (October 1992).
The binding molecule which binds to an oligosaccharide which is at least triantennary may be conjugated to a detectable marker or label. Examples of such detectable markers or labels include, but are not limited to, fluorescent labels, radioisotopes, such as, for example, isotopes of iodine, cobalt, or tritium, spin labels, chemiluminescent materials, enzymes, absorbing dyes, biotin, or colored particles.
After the bound PSA is contacted with the labeled binding molecule, the free (unbound) binding molecule is separated from the binding molecule which has been bound. The presence of prostate specific antigen having linked oligosaccharides which are at least triantennary then is determined by detecting the label of the binding molecule that is bound to oligosaccharides which are at least triantennary, said oligosaccharides being linked to prostate specific antigen. Such presence may be determined by means known to those skilled in the art, such means being dependent upon the type of label employed. The presence of a label indicates that the bound PSA includes linked oligosaccharide which is at least triantennary, with the presence of such structure being indicative of prostate cancer.
In accordance with another aspect of the present invention, there is provided a kit or package for detecting prostate specific antigen linked to an oligosaccharide which is at least triantennary. The kit includes (a) a solid support upon which is supported a binder, in particular, an antibody, which recognizes an epitope of prostate specific antigen; and (b) a binding molecule having a label such as those hereinabove described, wherein the binding molecule binds oligosaccharides that are at least triantennary but are not monoantennary or diantennary.
Solid supports which may be employed include, but are not limited to, those made of cellulosic materials such as paper, cellulose, and cellulose derivatives such as cellulose acetate and nitrocellulose; silica; fiberglass; inorganic materials such as deactivated aluminum, diatomaceous earth, or other inorganic finely divided material dispersed uniformly in a porous polymer matrix made of polymers such as vinyl chloride-propylene copolymer and vinyl chloride-vinyl acetate copolymer; cotton; nylon; porous gels such as silica gel, agarose, dextran, and gelatin; polymeric films such as polyacrylamide; magnetic particles; microtiter plates; polystyrene tubes; protein-binding membranes; Sephadex (Pharmacia Fine Chemicals, Inc., Piscataway, N.J.); Trisacryl (Pointet-Girard); silicon particles; polystyrene particles; vinyl chloride particles; latex particles; and porous fibrous matrices. In one embodiment, the solid support includes synthetic microparticles of polystyrene, vinyl chloride, or latex, having a diameter of 0.1 to 10 microns.
In another alternative, two assays are conducted. The first assay involves an inhibition assay. In such an assay, a compound or binding molecule, such as those hereinabove described, which binds to oligosaccharides which are at least triantennary, but does not bind oligosaccharides which are monoantennary or diantennary, is incubated with a predetermined amount of a first portion of a sample suspected of containing prostate specific antigen. After such incubation, the sample is contacted with an antibody supported on a solid support. The supported antibody, which may be a monoclonal or polyclonal antibody, recognizes an epitope of prostate specific antigen which, if an oligosaccharide which is at least triantennary is present on the prostate specific antigen, is proximal to such oligosaccharide of prostate specific antigen which is at least triantennary, whereby binding of the PSA antigen to the supported antibody is inhibited by the compound which binds to the oligosaccharide which is at least triantennary. If prostate specific antigen having linked oligosaccharides which are at least triantennary is present in such sample, such prostate specific antigen will not be able to bind to the supported antibody due to the previous binding of the compound or binding molecule which binds oligosaccharides which are at least triantennary. If there is prostate specific antigen present in the sample which does not include oligosaccharides which are at least triantennary, such prostate specific antigens will bind to the solid support. Thus, any prostate specific antigen which binds to the supported antibody is prostate specific antigen which does not have linked oligosaccharides which are at least triantennary.
Bound PSA then is separated from free PSA. The sample then is contacted with a labeled antibody which recognizes an epitope of prostate specific antigen. Thus, the labeled antibody binds to prostate specific antigen which has been bound by the supported antibody. Bound labeled antibody then is separated from free labeled antibody. The amount of bound labeled antibody to prostate specific antigen then is determined.
In the second assay, which is a sandwich assay, the antibody to prostate specific antigen which is supported on a solid support is contacted with a second portion of the sample suspected of containing prostate specific antigen. The second portion contains an amount of sample identical to that of the first portion. After the sample has contacted the solid support, the labeled antibody to prostate specific antigen is added, and the amount of bound labeled antibody is determined. If the amounts of bound labeled antibody in the first assay and the second assay are the same, then no prostate specific antigen linked to an oligosaccharide which is at least triantennary is present in the sample. If the amount of bound labeled antibody in the second assay is greater than that in the first assay, then prostate specific antigen which is linked to an oligosaccharide which is triantennary is present in the sample.
Thus, in accordance with a further aspect of the present invention, there is provided a kit or package for detecting prostate specific antigen linked to an oligosaccharide which is at least triantennary. The kit includes a pair of solid supports. Each support includes a binder, in particular, an antibody, which recognizes an epitope of prostate specific antigen. The epitope is located proximal to an oligosaccharide which is at least triantennary, if such an oligosaccharide is present on the prostate specific antigen. The kit also includes a binding molecule, such as hereinabove described, which binds to an oligosaccharide which is at least triantennary, but does not bind to oligosaccharides which are monoantennary or diantennary. The kit also includes a labeled antibody which recognizes an epitope of prostate specific antigen.
In another alternative, a sample suspected of containing prostate specific antigen is subjected to immunoprecipitation or to immunoaffinity purification using an antibody which recognizes prostate specific antigen. Isolated prostate specific antigen then is subjected to gel electrophoresis, such as, for example, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and transferred to an appropriate membrane, such as a polyvinylidene fluoride (PVDF) membrane. Appropriate bands then are excised from the membrane, and treated with an exoglycosidase or with a combination of an exoglycosidase and a neuraminidase to release the oligosaccharides from the prostate specific antigen. The oligosaccharides then are labeled and then analyzed through separation of the oligosaccharides on a gel. The gel then is analyzed for the presence of oligosaccharides which are at least triantennary.
Although the present invention has been described with respect to the diagnosis of cancer of the prostate through the detection of prostate specific antigen having linked oligosaccarides which are at least triantennary, the method of the present invention may be employed to detect antigens having linked oligosaccharides which are at least triantennary, and which are associated with cancer other than cancer of the prostate, such as, for example, breast and colon cancer. Such antigens may be detected by methods such as those hereinabove described with respect to the detection of the prostate specific antigen having linked oligosaccharides which are at least triantennary.

Detection of prostate and other cancers by assaying for cancer-specific antigens having linked oligosaccharides which are at least triantennary


A method and apparatus for use in creating a magnetic declination profile for a borehole. The method includes the steps of making a magnetic directional measurement at a longitudinal location in the borehole and at a magnetic measurement orientation, making a reference directional measurement at a reference measurement orientation, wherein there is a known orientation relationship between the magnetic measurement orientation and the reference measurement orientation, and obtaining a value of magnetic declination at the longitudinal location in the borehole using the magnetic directional measurement, the reference directional measurement and the orientation relationship. The apparatus includes a magnetic instrument for making a magnetic directional measurement, a magnetic orientation calibration indicator associated with the magnetic instrument for providing a magnetic instrument calibration orientation, a reference instrument linked with the magnetic instrument for making a reference directional measurement and a reference orientation calibration indicator associated with the reference instrument for providing a reference instrument calibration orientation.

A method and apparatus for use in creating a magnetic declination profile for a borehole, which magnetic declination profile can be used to correct directional measurements made in the borehole with magnetic instruments.
Measuring devices and methods used in boreholes typically make use of one or more earth fields in order to provide measurements for the inclination and direction of a borehole and for the orientation of objects located in the borehole.
The inclination of a borehole is sometimes referred to as the xe2x80x9cdriftxe2x80x9d of the borehole and is an expression of the deviation of the borehole from vertical (i.e., from the direction of the earth""s gravity vector).
The direction of a borehole is sometimes referred to as the xe2x80x9cazimuthxe2x80x9d of the borehole and is an expression of the direction of the borehole in a horizontal plane relative to a calibration direction such as magnetic North or true North.
The orientation of a point or object in a borehole is sometimes referred to as the xe2x80x9ctoolfacexe2x80x9d of the point or object and is an expression of the orientation of the point or object in a plane perpendicular to the longitudinal axis of the borehole relative to a reference orientation.
A variety of measuring instruments have evolved for the measurement of inclination and direction of a borehole and the orientation of points or objects in the borehole.
Inclination measurements in a borehole are commonly made with instruments that are sensitive to the earth""s gravity field. Such gravity instruments include, for example, plumb bobs and accelerometers and are typically capable of measuring the amount of vertical deviation of the borehole but not the direction of the vertical deviation.
Directional measurements in a borehole are commonly made with instruments which are sensitive to the earth""s magnetic field. Such magnetic instruments include, for example, compasses and magnetometers. Magnetic instruments are typically capable of providing a measurement of the direction of the borehole in a borehole coordinate system, but are unable to convert this measurement to a direction or azimuth of the borehole in a more useful reference coordinate system which is defined by the direction of the gravity vector and by compass directions in a plane perpendicular to the gravity vector.
The reference coordinate system conventionally has its X-axis parallel to the earth""s surface and pointing North, its Y-axis parallel to the earth""s surface and pointing East, and its Z-axis perpendicular to the earth""s surface and pointing vertically down.
The borehole coordinate system is conventionally described as having its z-axis along the borehole axis, its y-axis parallel to the earth""s surface and its x-axis perpendicular to both the y and z axes.
As a result, measurements taken with instruments which are sensitive to the earth""s magnetic field are typically converted to values corresponding with the reference coordinate system in order to provide enhanced survey accuracy. Conventionally, this conversion is carried out by using data relating to the inclination of the borehole to transform data relating to the direction of the borehole in the borehole coordinate system to values expressed in the reference coordinate system.
Measurements of the orientation of a point or object in a borehole may be made with gravity instruments. For example, the xe2x80x9chigh sidexe2x80x9d or the xe2x80x9clow sidexe2x80x9d of a borehole can be determined with instruments which are sensitive to the earth""s gravity field.
Measurements of the orientation of a point or object in a borehole may also be made with magnetic instruments. Such measurements are sometimes referred to as xe2x80x9cmagnetic toolfacexe2x80x9d measurements and are essentially an expression of the orientation of the point or object relative to the x and y axes in the borehole coordinate system.
As a result of the above, borehole survey apparatus often include gravity instruments which are sensitive to the earth""s gravity field as well as magnetic instruments which are sensitive to the earth""s magnetic field so that the apparatus are capable of providing measurements of the inclination and direction of the borehole as well as the orientation of points or objects in the borehole.
Survey apparatus of the type described above are typically quite rugged and capable of enduring severe environmental conditions of vibration, heat and pressure. They are thus well suited to the rigors of use in downhole equipment such as drilling assemblies and measurement while drilling (MWD) systems.
Unfortunately, however, there are difficulties associated with the use of survey apparatus which include magnetic instruments. First, magnetic instruments take directional measurements relative to magnetic North instead of true North, with the result that magnetic directional measurements must be corrected so that they are expressed relative to true North. Such correction is typically performed empirically with the use of magnetic declination charts, thus complicating and contributing a source of error to the resulting corrected measurement.
Second, survey apparatus including magnetic instruments are also not well suited for use in circumstances where interference with the earth""s magnetic field is present. For example, magnetic instruments are not commonly used for borehole surveys in boreholes which are lined with metal casing.
Furthermore, when magnetic instruments are used in drilling assemblies or MWD systems, they are typically isolated from the interfering magnetic effects of the drilling string by being contained in non-magnetic housings and by being located adjacent to non-magnetic drill collars or drill pipe. Despite such measures, error remains present in magnetic instrument measurements due to the influence of magnetic deposits (or the casing of nearby boreholes) in the formation being drilled and due to the effects of magnetism in the drilling string and the drilling assembly.
The effects of magnetism in the drilling string and the drilling assembly are reasonably well understood and numerous methods have been developed for addressing the measurement error resulting from these effects. Examples of such methods are found in U.S. Pat. No. 4,682,421 (van Dongen et al), U.S. Pat. No. 5,103,177 (Russell et al), U.S. Pat. No. 5,435,069 (Nicholson), U.S. Pat. No. 5,787,997 (Hartmann) and U.S. Pat. No. 5,806,194 (Rodney et al).
Some efforts have also been made to address the issues associated with orienting objects in a borehole using magnetic instruments where magnetic deposits or adjacent casing strings are present. Typically these methods are used to avoid adjacent boreholes during perforation operations or during drilling of a borehole and may in fact utilize the interfering effects caused. by such adjacent boreholes. Examples of such methods are found in U.S. Pat. No. 3,704,749 (Estes et al), U.S. Pat. No. 3,964,553 (Basham et al), U.S. Pat. No. 4,593,770 (Hoehn) and U.S. Pat. No. 5,582,248 (Estes).
Many of the difficulties associated with the use of magnetic instruments to take measurements in boreholes may be overcome by using instruments which take measurements which are not influenced by magnetic flux in the borehole. These instruments typically measure changes of direction relative to a calibration direction. One example of such an instrument is a conventional gyroscope, which can be oriented in a calibration direction and will then sense movement relative to the calibration direction.
Such xe2x80x9cnon-magneticxe2x80x9d instruments may also utilize an earth field vector to assist in establishing the calibration direction, such as the earth""s inertial angular velocity vector as described in U.S. Pat. No. 4,433,491 (Ott et al). One example of a xe2x80x9cnon-magneticxe2x80x9d instrument which makes use of the earth""s inertial angular velocity vector is a xe2x80x9cnorth seekingxe2x80x9d gyroscopic instrument, which is capable of taking directional measurements relative to true North.
Gyroscopic instruments of a variety of types are used frequently to survey existing boreholes and are particularly suited for use in boreholes containing casing, since gyroscopic instruments are not influenced by magnetic flux and in particular by magnetic interference caused by metallic casing. Gyroscopic instruments are also capable of taking relatively accurate and reliable measurements.
Unfortunately, however, gyroscopic instruments are not particularly rugged and are thus not well suited for use in drilling assemblies or in MWD systems. As a result, the use of gyroscopic instruments for taking measurements in boreholes is generally confined to lowering the gyroscopic instrument in the borehole on a wireline to take measurements before a downhole operation in the borehole has taken place or after such an operation has been completed. The actual downhole operation is performed either without measurements being taken or with the use of survey apparatus including magnetic instruments which inherently provide errors due to discrepancies between true North and magnetic North and magnetic effects of nearby magnetic deposits or adjacent casing strings.
There is therefore a need for a method and apparatus for creating a magnetic declination profile for a borehole which will assimilate errors which are inherent in measurements made by magnetic instruments, so that directional measurements made with magnetic instruments can easily be corrected to provide reliable directional information pertaining either to the direction of the borehole or the orientation of a point or object in the borehole.
The present invention is a method and apparatus for creating a magnetic declination profile for a borehole. The magnetic declination profile may include a value of magnetic declination at as few as one longitudinal location in the borehole. Preferably, however, the magnetic declination profile includes values of magnetic declination at more than one longitudinal location in the borehole.
The method involves making a magnetic directional measurement at a longitudinal location in the borehole, wherein the magnetic directional measurement is influenced by magnetic flux in the borehole. The magnetic directional measurement is made at a magnetic measurement orientation. The method further involves making a reference directional measurement, wherein the reference directional measurement is not influenced by magnetic flux in the borehole. The reference directional measurement is made at a reference measurement orientation, wherein there is an orientation relationship between the magnetic measurement orientation and the reference measurement orientation and wherein the orientation relationship is known or is ascertainable. A value of magnetic declination at the longitudinal location can then be obtained using the magnetic directional measurement, the reference directional measurement and the orientation relationship.
The magnetic directional measurement may be any directional measurement which is influenced by magnetic flux and which is directed at determining the direction of magnetic vectors. Preferably the magnetic directional measurement is directed at determining directions relative to the earth""s magnetic field vector but includes the effects of interfering magnetic vectors which could influence the magnetic directional measurement.
The reference directional measurement may be any directional measurement which is not influenced by magnetic flux. Preferably the reference directional measurement is directed at determining changes of direction relative to a calibration direction, which calibration direction may be provided by an earth field vector such as the earth""s inertial angular velocity vector or may be provided in some other manner.
The value of magnetic declination that is obtained using the invention may be a representation of the difference between true North and magnetic North at the longitudinal location if no sources of magnetic interference are present at the longitudinal location. Usually, however, the value of magnetic declination is a representation of any and all magnetic influences at the longitudinal location of the type which will result in the magnetic directional measurement being different from the reference directional measurement when the magnetic measurement orientation is the same as the reference measurement orientation.
In one method aspect of the invention, the invention is comprised of a method for creating a magnetic declination profile for a borehole comprising the steps of:
(a) making a first magnetic directional measurement at a first longitudinal location in the borehole, wherein the first magnetic directional measurement is influenced by magnetic flux and wherein the first magnetic directional measurement is made at a first magnetic measurement orientation;
(b) making a first reference directional measurement, wherein the first reference directional measurement is not influenced by magnetic flux, wherein the first reference directional measurement is made at a first reference measurement orientation, wherein there is a first orientation relationship between the first magnetic measurement orientation and the first reference measurement orientation and wherein the first orientation relationship is known or ascertainable; and
(c) obtaining a value of magnetic declination at the first longitudinal location in the borehole using the first magnetic directional measurement, the first reference directional measurement and the first orientation relationship.
The first magnetic directional measurement may be made using any method or apparatus which is influenced by magnetic flux. Preferably the first magnetic directional measurement is made using a magnetic instrument. The magnetic instrument may be comprised of a compass. Preferably the magnetic instrument is comprised of a magnetometer. In the preferred embodiment the magnetometer is a triaxial magnetometer which is capable of measuring magnetic flux along three mutually perpendicular axes. The first magnetic directional measurement provides an indication of the direction of the resultant magnetic field vector at the first longitudinal location and may optionally also provide an indication of the magnitude of the resultant magnetic field at the first longitudinal location.
The first reference directional measurement may be made using any method or apparatus which is not influenced by magnetic flux. The first reference directional measurement may be made using a reference instrument which measures changes of direction relative to a calibration direction. The calibration direction may be related or unrelated to the earth""s inertial angular velocity vector. Preferably the reference directional measurement is made with a reference instrument which is comprised of a gyroscopic instrument.
The step of obtaining the value of magnetic declination may be comprised of the steps of calculating a first measurement differential between the first magnetic directional measurement and the first reference directional measurement, calculating a first orientation differential between the first magnetic measurement orientation and the first reference measurement orientation, and adjusting the first measurement differential by the amount of the first orientation differential to obtain the value of magnetic declination at the first longitudinal location in the borehole.
The first orientation differential may be any amount or value but is preferably equal to zero so that the first measurement differential is equal to the value of magnetic declination at the first longitudinal location in the borehole. The first orientation differential may be established by linking the magnetic instrument and the reference instrument.
The invention may be used to create a magnetic declination profile in any borehole. The invention is, however, particularly well suited for use in boreholes having an inclination relative to vertical of less than about five degrees, since values of magnetic declination in such boreholes cannot conventionally be obtained effectively by combining magnetic directional measurements with data from previous borehole surveys indicating borehole inclination and azimuth. As a result, preferably the method is used to obtain a value of magnetic declination where the inclination of the borehole at the first longitudinal location is less than about five degrees.
In addition, although the invention may be used to create magnetic declination profiles in open or uncased boreholes, the invention is particularly suited for use in boreholes containing a metallic casing. The presence of metallic casing in the borehole will result in magnetic interference which can be assimilated into the magnetic declination profile. As a result, preferably the method is used to obtain a value of magnetic declination where the borehole is lined with a metallic casing at or in the proximity of the first longitudinal location.
The method may be used to create a magnetic declination profile for the borehole at only the first longitudinal location. Preferably, however, the method is performed at a plurality of longitudinal locations in the borehole in order to create a magnetic declination profile for the borehole at the plurality of longitudinal locations.
For example, the method may be performed at a second longitudinal location in the borehole by performing the following steps:
(d) making a second magnetic directional measurement at a second longitudinal location in the borehole, wherein the second magnetic directional measurement is influenced by magnetic flux and wherein the second magnetic directional measurement is made at a second magnetic measurement orientation;
(e) making a second reference directional measurement, wherein the second reference directional measurement is not influenced by magnetic flux, wherein the second reference directional measurement is made at a second reference measurement orientation, wherein there is a second orientation relationship between the second magnetic measurement orientation and the second reference measurement orientation and wherein the second orientation relationship is known; and
(f) obtaining a value of magnetic declination at the second longitudinal location in the borehole using the second magnetic directional measurement, the second reference directional measurement and the second orientation relationship.
Similarly, the step of obtaining the value of magnetic declination at the second longitudinal location may be comprised of the following steps:
(d) calculating a second measurement differential between the second magnetic directional measurement and the second reference directional measurement;
(e) calculating a second orientation differential between the second magnetic measurement orientation and the second reference measurement orientation; and
(f) adjusting the second measurement differential by the amount of the second orientation differential to obtain the value of magnetic declination at the second longitudinal location in the borehole.
The second orientation relationship may be different from the first orientation relationship, but preferably the second orientation relationship and the first orientation relationship are the same so that the second orientation differential is equal to the first orientation differential.
In an apparatus aspect of the invention, the invention is comprised of an apparatus for use in creating a magnetic declination profile for a borehole comprising:
(a) a magnetic instrument for making a magnetic directional measurement which is influenced by magnetic flux;
(b) a magnetic orientation calibration indicator associated with the magnetic instrument for providing a magnetic instrument calibration orientation;
(c) a reference instrument for making a reference directional measurement which is not influenced by magnetic flux; and
(d) a reference orientation calibration indicator associated with the reference instrument for providing a reference instrument calibration orientation;
wherein the magnetic instrument and the reference instrument are linked such that a constant indicator differential can be maintained between the magnetic orientation calibration indicator and the reference orientation calibration indicator.
The reference instrument may be comprised of any apparatus or device which is capable of making a directional measurement which is not influenced by magnetic flux. Preferably the reference instrument is comprised of a gyroscopic instrument.
The magnetic instrument calibration orientation provided by the magnetic orientation calibration indicator may be referenced to any calibration direction, but is preferably referenced to some known direction relative to magnetic North. Most preferably, the magnetic orientation calibration indicator is configured so that the magnetic instrument indicates magnetic North when the magnetic orientation calibration indicator is pointed at magnetic North (in the absence of sources of magnetic interference).
The reference instrument calibration orientation provided by the reference orientation calibration indicator may be referenced to any calibration direction, but is preferably referenced to some known direction relative to true North. Most preferably, the reference orientation calibration indicator is configured so that the reference instrument indicates true North when the reference orientation calibration indicator is pointed at true North.
The magnetic orientation calibration indicator may be aligned with the reference orientation calibration indicator to provide any amount of indicator differential. Preferably, however, the magnetic orientation calibration indicator is aligned with the reference orientation calibration indicator such that the indicator differential is equal to zero.
The magnetic instrument and the reference instrument are each preferably contained in a housing, which housing adjacent to the magnetic instrument is preferably comprised substantially of a non-magnetic material so that the housing does not provide a source of magnetic interference. The housing may be comprised of a single housing section or may be comprised of a plurality of housing sections.
The apparatus may be lowered into the borehole in any manner, and may be incorporated into a pipe string. Preferably, however, the apparatus is lowered into the borehole on a wireline. The apparatus is preferably further comprised of a connector for connecting the apparatus to the wireline or to a pipe string.
Preferably the distance between the reference instrument and the magnetic instrument is minimized in order to reduce the likelihood of error due to misalignment of the instruments or due to bending or other deformation of the apparatus during use.
In the preferred embodiment, however, the reference instrument is separated longitudinally from the magnetic instrument to minimize the likelihood of either instrument interfering with the measurements of the other instrument. In the preferred embodiment, the amount of longitudinal separation between the instruments is preferably a convenient distance such as one meter or a multiple of one meter so that the position of the reference instrument in the borehole can easily be calculated from the position of the longitudinal locations at which magnetic measurements are made, and vice versa.
This in turn assists in the creation of the magnetic declination profile, particularly where the magnetic instrument and the reference instrument collect other data which is not directly related to the creation of the magnetic declination profile, since such other data may be used to provide a survey of the borehole which in turn may possibly be used to verify the measurements of the magnetic instrument and the reference instrument.
In a further method aspect of the invention, the invention is comprised of a method for conducting a magnetic declination survey for a borehole, the method comprising the following steps:
(a) connecting a magnetic instrument with a gyroscopic instrument to provide a magnetic declination logging tool;
(b) aligning a magnetic orientation calibration indicator associated with the magnetic instrument with a reference orientation calibration indicator associated with the gyroscopic instrument to provide a known first indicator differential between the magnetic orientation calibration indicator and the reference orientation calibration indicator;
(c) lowering the magnetic declination logging tool into the borehole to position the magnetic instrument at a first longitudinal location;
(d) making a first magnetic directional measurement with the magnetic instrument at the first longitudinal location;
(e) making a first reference directional measurement with the gyroscopic instrument; and
(f) obtaining a value of magnetic declination at the first longitudinal location in the borehole using the first magnetic directional measurement, the first reference directional measurement and the first indicator differential.
This further method aspect of the invention combines the features of the method and apparatus aspects of the invention described above.

Method and apparatus for use in creating a magnetic declination profile for a borehole


The image forming system includes: a first transporting unit transporting paper sheets along a first transportation route; an image forming unit forming images on the paper sheets; a sheet supplying unit having a second transportation route, and transporting a sheet along the second transportation route to supply the sheet to a gap between the paper sheets sequentially transported along the first transportation route, the second transportation route joining the first transportation route at a position located on a downstream of the image forming unit in a transportation direction; and a controller outputting, to respective first and second output units, a paper sheet located on a downstream of the gap, and a paper sheet located on an upstream of the gap while causing the image forming unit to form an image on the paper sheet on the upstream of the image forming unit, when the sheet is not supplied.

1. Technical Field
The present invention relates to an image forming system forming an image on a paper sheet, and a paper sheet output method.
2. Related Art
There has been proposed a technique in which recording papers left in a transportation route upon occurrence of jamming are tried to be reused.

Image forming system and paper sheet output method


A semiconductor device including a switching device such as a MOSFET or an IGBT, and an avalanche device for protecting the switching device by generating an avalanche current when an overvoltage is applied to the switching device. The avalanche device shares a drift layer, that is, an epitaxial layer with the switching device. With this arrangement, the avalanche voltage of the avalanche device follows changes in the withstanding voltages of the switching device due to variations in the thickness or impurity concentration of the epitaxial layer or temperature. This makes it possible to reduce the margin between the avalanche voltage of the avalanche device and the withstanding voltage of the switching device, and to positively protect the switching device from damage.

1. Field of the Invention
The present invention relates to a power switching device used for controlling a motor or the like, and more particularly to a semiconductor device including a switching device and an overvoltage protective circuit.
2. Description of the Prior Art
FIG. 1 is a circuit diagram showing a semiconductor device including a conventional overvoltage protective circuit. The semiconductor device employs an n-channel MOSFET 1 as a switching device connected between load terminals 5 and 6. An overvoltage protective circuit 40 is provided for protecting the MOSFET 1 from an overvoltage. The overvoltage protective circuit 40 comprises an avalanche diode 2 that generates an avalanche current when an overvoltage is applied, and a current limiting resistor-diode 3 for restricting the avalanche current. The diode and resistor are connected in series between the drain electrode D and the gate electrode G of the MOSFET 1. In addition, a reference (Zener) diode 4 for protecting the gate electrode G from the overvoltage is connected between the gate electrode G and the source electrode S. Furthermore, the gate voltage is applied from a control input terminal 9 to the gate electrode G through a gate resistor 8. Thus, the MOSFET 1 is controlled to enter the OFF state, that is, the voltage blocking state by applying a low gate voltage.
Unless the overvoltage protective circuit 40 for protecting the MOSFET 1 from an overvoltage is provided an overvoltage that exceeds the withstanding voltage of the MOSFET 1 applied thereto will cause the avalanche current to flow through the MOSFET 1, resulting in damage of the MOSFET 1 when the avalanche current is excessively large. Generally, the avalanche current intensely flows through locations where the electric field is concentrated such as locations where the curvature of the PN junction is small, which PN junction is formed to establish the withstanding voltage. Accordingly, the current density is liable to increase in such locations. This may often cause damage of the MOSFET 1 even if the avalanche current is rather small per se.
On the other hand, the overvoltage protective circuit 40 as shown in FIG. 1 can protect the MOSFET 1 from such damage by setting the avalanche voltage of the avalanche diode 2 below the withstanding voltage of the MOSFET 1. More specifically, by setting the withstanding voltage of the avalanche diode 2 below that of the MOSFET 1, the avalanche current flows first through the avalanche diode 2 rather than the MOSFET 1 when overvoltage occurs across the load terminals 5 and 6. Since the avalanche current flows through the gate resistor 8 to the control input terminal 9, a voltage drop takes place across the gate resistor 8. Thus, the gate voltage increases and the MOSFET 1 conducts. As a result, the energy of the overvoltage across the load terminals 5 and 6 is absorbed in the form of the ON current of the MOSFET 1. This reduces the voltage across the load terminals 5 and 6, which in turn drops the avalanche current flowing through the avalanche diode 2. Thus, the MOSFET 1 tries to change into the OFF state again. In practice, however, the avalanche current of the avalanche diode 2 balances the current flowing through the MOSFET 1 so that a constant current flows through the MOSFET 1, which current is determined by factors such as the impedance of the voltage source supplying the overcurrent. Thus, the overvoltage protective circuit 40 protects the MOSFET 1 from the overvoltage by preventing the avalanche current from flowing through the MOSFET 1. Further, as long as the impedance of the voltage source is not too small, the avalanche current flowing through the avalanche diode 2 does not increase to a degree that damages the diode 2, thereby protecting the semiconductor device in its entirety.
Thus, the semiconductor device comprising such an overvoltage protective circuit can protect the switching device from damage by setting the avalanche voltage of the avalanche diode 2 below the withstanding voltage of the switching device. However, considering variations in the avalanche voltage of the avalanche diode, the withstanding voltage of the switching device must be set sufficiently higher than the avalanche voltage. The high withstanding voltage of the switching device, however, increases the ON state voltage and the switching loss of the switching device because the high withstanding voltage requires a thick drift layer through which the depletion layer spreads.
Furthermore, with regard to bipolar devices such as an IGBT (Insulated Gate Bipolar Transistor), when an inductive load such as a motor is turned off, an overvoltage takes place across the emitter and collector because of the -di/dt due to the inductive component such as stray reactance. As a result, although the gate voltage begins to drop and the current begins to reduce in this case, the base voltage of the NPN transistor constituting the IGBT increases. This causes a constant drain current to continue to flow. Thus, the minority carrier moves through the depletion layer spreading through the PN junction, and the electric charges of the minority carrier strengthen the electric field in the depletion layer. Accordingly, it is necessary to consider the reduction in the withstanding voltage from the static withstanding voltage in the IGBT or the like in the case of a turnoff operation. This will require a further increase in the margin between the withstanding voltage of the switching device and the avalanche voltage. As a result, the device characteristics such as an ON state voltage of the bipolar devices like an IGBT tend to be further degraded.

Semiconductor device including overvoltage protective circuit


Methods for producing modified polypeptides containing amino acid analogues are disclosed. The invention further provides purified dihydrofolate reductase polypeptides, produced by the methods of the invention, in which the methionine residues have been replaced with homoallylglycine, homoproparglycine, norvaline, norleucine, cis-crotylglycine, trans-crotylglycine, 2-aminoheptanoic acid, 2-butynylglycine and allylglycine.

1. Field of the Invention
The present invention relates to novel compositions and methods, for incorporating amino acid analogues into proteins in vivo, by overexpression of aminoacyl-tRNA synthetases.
2. Description of the Related Art
Expanding the scope of biological polymerizations to include non-natural monomers is an area of growing interest, with important theoretical and practical consequences. An early and critically important example of such studies was the demonstration that "dideoxy" nucleotide monomers can serve as substrates for DNA polymerases. Advances in DNA sequencing (F. Sanger, S, Nicklen, A. R. Coulson, Proc. Natl. Acad. Sci. USA 1977, 74, 5463-5467), DNA base pairing models (M. J. Lutz, S. A. Benner, S. Hein, G. Breipohl, E. Uhlmann, J. Am. Chem. Soc. 1997, 119, 3177-3178; J. C. Morales, E. T. Kool, Nature Struct. Biol. 1998, 5, 950-954), materials synthesis (W. H. Park, R. W. Lenz, S. Goodwin, Macromolecules 1998, 31, 1480-1486; Y. Doi, S. Kitamura, H. Abe, Macromolecules 1995, 28, 4822-4828), and cell surface engineering (K. J. Yarema, L. K. Mahal, R. E. Bruehl, E. C. Rodriguez, C. R. Bertozzi, J. Biol. Chem. 1998, 273, 31168-31179; L. K. Mahal, K. J. Yarema, C. R. Bertozzi, Science 1997, 276, 1125-1128; Saxon, E. and Bertozzi, C. R. Science 2000, 287, 2007-2010) have resulted from the recognition of non-natural monomers by the enzymes that control these polymerizations.
Recent investigations have shown the incorporation of modified or completely "synthetic" bases into nucleic acids (Matray, T. J.; Kool, E. T. Nature 1999, 399, 704; Kool, E. T. Biopolymers 1998, 48, 3; Morales, J. C.; Kool, E. T. Nature Struct. Biol. 1998, 5, 950; Guckian, K. M.; Kool, E. T.; Angew. Chem. Int. Ed. Eng. 1998, 36, 2825; Liu, D. Y.; Moran, S.; Kool, E. T. Chem. Biol. 1997, 4, 919; Moran, S.; Ren, R. X. F.; Kool, E. T. Proc. Natl. Acad. Sci. USA 1997, 94, 10506; Moran, S. et al. J. Am. Chem. Soc. 1997, 119, 2056; Benner, S. A. et al. Pure Appl. Chem. 1998, 70, 263; Lutz, M. J.; Horlacher J.; Benner, S. A. Bioorg. Med. Chem. Lett. 1998, 8, 1149; Lutz, M. J.; Held, H. A.; Hottiger, M.; Hubscher, U.; Benner, S. A. Nuc. Acids Res. 1996, 24, 1308; Horlacher, J. et al. Proc. Natl. Acad. Sci. USA 1995, 92, 6329; Switzer, C. Y.; Moroney, S. E.; Benner, S. A. Biochemistry 1993, 32, 10489; Lutz, M. J.; Horlacher, J.; Benner, S. A. Bioorg. Med. Chem. Lett. 1998, 8, 499; Switzer, C.; Moroney, S. E.; Benner, S. A. J. Am. Chem. Soc. 1989, 111, 8322; Piccirilli, J. A.; Krauch, T.; Moroney, S. E.; Benner, S. A. Nature 1990, 343, 33), while materials researchers have exploited the broad substrate range of the poly(β-hydroxyalkanoate) (PHA) synthases to prepare novel poly(β-hydroxyalkanoate)s (PHAs) with unusual physical properties (Kim, Y. B.; Rhee, Y. H.; Lenz, R. W. Polym. J. 1997, 29, 894; Hazer, B.; Lenz, R. W.; Fuller, R. C. Polymer 1996, 37, 5951; Lenz, R. W.; Kim, Y. B.; Fuller, R. C. FEMS Microbiol. Rev. 1992, 103, 207; Park, W. H.; Lenz, R. W.; Goodwin, S. Macromolecules 1998, 31, 1480; Ballistreri, A. et al. Macromolecules 1995, 28, 3664; Doi, Y.; Kitamura, S.; Abe, H. Macromolecules 1995, 28, 4822).
Novel polymeric materials with unusual physical and/or chemical properties are also useful in polymer chemistry. The last several decades have shown many advances in synthetic polymer chemistry that provide the polymer chemist with increasing control over the structure of macromolecules (Szwarc, M. Nature 1956, 178, 1168-1169 Szwarc, M. Nature 1956, 178, 1168-1169; Faust, R.; Kennedy, J. P. Polym. Bull. 1986, 15, 317-323; Schrock, R. R. Acc. Chem. Res. 1990, 23, 158-165; Corradini, P. Macromol. Symp. 1995, 89, 1-11; Brintzinger, H. H.; Fischer, D.; Mulhaupt, R.; Rieger, B.; Waymouth, R. M. Angew. Chem. Int. Ed. Engl. 1995, 34, 1143-1170; Dias, E. L.; SonBinh, T. N.; Grubbs, R. H. J. Am. Chem. Soc. 1997, 119, 3887-3897; Chiefari, J. et al. Macromolecules 1998, 31, 5559-5562). However, none of these methods have provided the level of control that is the basis of the exquisite catalytic, informational, and signal transduction capabilities of proteins and nucleic acids (Ibba, M.; Soll, D. Science 1999, 286, 1893-1897). There remains a need for control over protein synthesis to design and produce artificial proteins having advantageous properties.
For this reason, the design and synthesis of artificial proteins that exhibit novel and potentially useful structural properties have been investigated. Harnessing the molecular weight and sequence control provided by in vivo synthesis would permit control of folding, functional group placement, and self-assembly at the angstrom length scale. Proteins that have been produced by in vivo methods exhibit predictable chain-folded lamellar architectures (Krejchi, M. T.; Atkins, E. D. T.; Waddon, A. J.; Fournier, M. J.; Mason, T. L.; Tirrell, D. A. Science 1994, 265, 1427-1432; Parkhe, A. D.; Fournier, M. J.; Mason, T. L.; Tirrell, D. A. Macromolecules 1993, 26(24), 6691-6693; McGrath, K. P.; Fournier, M. J.; Mason, T. L.; Tirrell, D. A. J. Am. Chem. Soc. 1992, 114, 727-733; Creel, H. S.; Fournier, M. J.; Mason, T. L.; Tirrell, D. A. Macromolecules 1991, 24, 1213-1214), unique smectic liquid-crystalline structures with precise layer spacings (Yu, S. M.; Conticello, V.; Zhang, G.; Kayser, C.; Fournier, M. J.; Mason, T. L.; Tirrell, D. A. Nature 1997, 389, 187-190), and controlled reversible gelation (Petka, W. A.; Hardin, J. L.; McGrath, K. P.; Wirtz, D.; Tirrell, D. A. Science 1998, 281, 389-392). The demonstrated ability of these protein polymers to form unique macromolecular architectures will be of importance for engineering materials with interesting liquid-crystalline, crystalline, surface, electronic, and optical properties.
Novel chemical and physical properties that can be engineered into protein polymers may be expanded by the precise placement of amino acid analogues. Efforts to incorporate novel amino acids into proteins in vivo have relied on the ability of the translational apparatus to recognize amino acid analogues that differ in structure and functionality from the natural amino acids. The in vivo incorporation of amino acid analogues into proteins is controlled most stringently by the aminoacyl-tRNA synthetases (AARS), the class of enzymes that safeguards the fidelity of amino acid incorporation into proteins (FIG. 1). The DNA message is translated into an amino acid sequence via the pairing of the codon of the messenger RNA (mRNA) with the complementary anticodon of the aminoacyl-tRNA. Aminoacyl-tRNA synthetases control the fidelity of amino acid attachment to the tRNA. The discriminatory power of the aminoacyl-tRNA synthetase places severe limits on the set of amino acid structures that can be exploited in the engineering of natural and artificial proteins in vivo.
Several strategies for circumventing the specificity of the synthetases have been explored. Introduction of amino acid analogues can be achieved relatively simply via solid-phase peptide synthesis (Merrifield, R. B. Pure & Appl. Chem. 1978, 50, 643-653). While this method circumvents all biosynthetic machinery, the multistep procedure is limited to synthesis of peptides less than or equal to approximately 50 amino acids in length, and is therefore not suitable for producing protein materials of longer amino acid sequences.
Chemical aminoacylation methods, introduced by Hecht and coworkers (Hecht, S. M. Acc. Chem. Res. 1992, 25, 545; Heckler, T. G.; Roesser, J. R.; Xu, C.; Chang, P.; Hecht, S. M. Biochemistry 1988, 27, 7254; Hecht, S. M.; Alford, B. L.; Kuroda, Y.; Kitano, S. J. Biol. Chem. 1978, 253, 4517) and exploited by Schultz, Chamberlin, Dougherty and others (Cornish, V. W.; Mendel, D.; Schultz, P. G. Angew. Chem. Int. Ed. Engl. 1995, 34, 621; Robertson, S. A.; Ellman, J. A.; Schultz, P. G. J. Am. Chem. Soc. 1991, 113, 2722; Noren, C. J.; Anthony-Cahill, S. J.; Griffith, M. C.; Schultz, P. G. Science 1989, 244, 182; Bain, J. D.; Glabe, C. G.; Dix, T. A.; Chamberlin, A. R. J. Am. Chem. Soc. 1989, 111, 8013; Bain, J. D. et al. Nature 1992, 356, 537; Gallivan, J. P.; Lester, H. A.; Dougherty, D. A. Chem. Biol. 1997, 4, 740; Turcatti, et al. J. Biol. Chem. 1996, 271, 19991; Nowak, M. W. et al. Science, 1995, 268, 439; Saks, M. E. et al. J. Biol. Chem. 1996, 271, 23169; Hohsaka, T. et al. J. Am. Chem. Soc. 1999, 121, 34), avoid the synthetases altogether, but provide low protein yields.
Alteration of the synthetase activities of the cell is also possible, either through mutagenesis or through introduction of heterologous synthetases (Ibba, M.; Hennecke, H. FEBS Lett. 1995, 364, 272; Liu, D. R.; Maghery, T. J.; Pastrnak, M.; Schultz, P. G. Proc. Natl. Acad. Sci. USA, 1997, 94, 10092; Furter, R. Protein Sci. 1998, 7, 419; Ohno, S. et al., J. Biochem. 1998, 124, 1065; Liu, D. R.; Schultz, P. G. Proc. Natl. Acad. Sci. 1999, 96, 4780; Wang, L.; Magliery, T. J.; Liu, D. R.; Schultz, P. G. J. Am. Chem. Soc. 2000, 122, 5010-5011; Pastrnak, M.; Magliery, T. J.; Schultz, P. G. Helv. Chim. Acta 2000, 83, 2277-2286).
In some instances, the ability of the wild-type synthetases to accept amino acid analogues has been exploited. For example, wild-type synthetases have been shown to activate and charge substrates other than the canonical, proteinogenic amino acids (Cowie, D. B.; Cohen, G. N. Biochim. Biophys. Acta. 1957, 26, 252; Richmond, M. H. Bacteriol Rev. 1962, 26, 398; Horton, G.; Boime, I. Methods Enzymol. 1983, 96, 777; Wilson, M. J.; Hatfield, D. L. Biochim. Biophys. Acta 1984, 781, 205). This approach offers important advantages with respect to synthetic efficiency, in that neither chemical acylation of tRNA nor cell-free translation is required. The simplicity of the in vivo approach, its relatively high synthetic efficiency, and its capacity for multisite substitution, make it the method of choice for production of protein materials whenever possible.
The capacity of the wild-type translational apparatus has been previously demonstrated to utilize amino acid analogues bearing fluorinated (Richmond, M. H. J. Mol. Biol. 1963, 6, 284; Fenster, E. D.; Anker, H. S. Biochemistry 1969, 8, 268; Yoshikawa, E.; Fournier, M. J.; Mason, T. L.; Tirrell, D. A. Macromolecules 1994, 27, 5471), unsaturated (Van Hest, J. C. M.; Tirrell, D. A. FEBS Lett. 1998, 428, 68; Deming, T. J.; Fournier, M. J.; Mason, T. L.; Tirrell, D. A. J. Macromol. Sci.—Pure Appl. Chem. 1997, A34, 2134), electroactive (Kothakota, S.; Mason, T. L.; Tirrell, D. A.; Fournier, M. J. J. Am. Chem. Soc. 1995, 117, 536), and other useful side chain functions. The chemistries of the above functional groups are distinct from the chemistries of the amine, hydroxyl, thiol, and carboxylic acid functional groups characteristic of proteins; this makes their incorporation particularly attractive for targeted chemical modification of proteins.
For example, alkene functionality introduced into artificial proteins via dehydroproline can be quantitatively modified via bromination and hydroxylation (Deming, T. J.; Fournier, M. J.; Mason, T. L.; Tirrell, D. A. J. Macromol. Sci. Pure Appl. Chem. 1997, A34, 2143-2150). Alkene functionality, introduced by incorporation of other amino acid analogues, should be useful for chemical modification of proteins by olefin metathesis (Clark, T. D.; Kobayashi, K.; Ghadiri, M. R. Chem. Eur. J. 1999, 5, 782-792; Blackwell, H. E.; Grubbs, R. H. Angew. Chem. Int. Ed. Engl. 1998, 37, 3281-3284), palladium-catalyzed coupling (Amatore, C.; Jutand, A. J. Organomet. Chem. 1999, 576, 255-277; Tsuji, J. Palladium Reagents and Catalysts: Innovations in Organic Synthesis; John Wiley and Sons: New York, 1995; Schoenberg, A.; Heck, R. F. J. Org. Chem. 1974, 39, 3327-3331), and other chemistries (Trost, B. M.; Fleming, I., Eds. Comprehensive Organic Synthesis; Pergamon Press: Oxford, 1991). The incorporation of fluorinated functional groups into proteins has imparted to protein films the low surface energy characteristic of fluoropolymers; contact angles of hexadecane on fluorinated protein polymers (70°) are much higher than, those on unfluorinated controls (17°) (Yoshikawa, E.; Fournier, M. J.; Mason, T. L.; Tirrell, D. A. Macromolecules 1994, 27, 5471-5475).
Methionine (1) (FIG. 1) is a possible target for substitution by amino acid analogues, with its hydrophobicity and polarizability, make it an important amino acid for regulating protein structure and protein-protein recognition processes (T. Yuan, A. M. Weljie, H. J. Vogel, Biochemistry 1998, 37, 3187-3195; H. L. Schenck, G. P. Dado, S. H. Gellman, J. Am. Chem. Soc. 1996, 118, 12487-12494; Maier, K. L.; Lenz, A. G., Beck-Speier, I.; Costabel, U. Methods Enzymol. 1995, 251, 455-461). Replacement of methionine by its analogues may therefore permit purposeful manipulation of these properties.
Several analogues of methionine (1), specifically selenomethionine, telluromethionine, norleucine, trifluoromethionine and ethionine (Hendrickson, W. A.; Horton, J. R.; Lemaster, D. M. EMBO J. 1990, 9, 1665; Boles, J. O. et al. Nature Struct. Biol. 1994, 1, 283; Cowie, D. B.; Cohen, G. N.; Bolton, E. T.; de Robichon-Szulmajster, H. Biochim. Biophys. Acta 1959, 34, 39; Duewel, H.; Daub, E.; Robinson, R.; Honek, J. F. Biochemistry 1997, 36, 3404; Budisa, N.; Steipe, B.; Demange, P.; Eckerskorn, C.; Kellerman, J.; Huber, R. Eur. J. Biochem. 1995, 230, 788), have been shown to exhibit translational activity in bacterial hosts. Incorporation of selenomethionine in place of methionine has long been known to facilitate protein structure determination by x-ray crystallography (Wei, Y.; Hendrickson, W. A.; Crouch, R. J.; Satow, Y. Science 1990, 249, 1398-1405).
However, only a limited number of amino acid analogues have been shown to conclusively exhibit translational activity in vivo, and the range of chemical functionality accessible via this route remains modest. These circumstances dictate a need for a systematic search for new amino acid analogues and strategies that will allow the engineering of proteins with novel chemical and physical properties.

This patent is subject to a terminal disclaimer.

Overexpression of aminoacyl-tRNA synthetases for efficient production of engineered proteins containing amino acid analogues


Porphyrin complex compounds, consisting of a mesotetraphenylporphyrin ligand, optionally at least one ion of an element with atomic numbers 13, 21, 32, 37-39, 42-44, 49, 50 or 57-83 as well as optionally cations of inorganic and/or organic bases, amino acids or amino acid amides, are valuable diagnostic and therapeutic agents.

The invention relates to mesotetraphenylporphyrin complex compounds, new pharmaceutical agents containing these compounds, their use in diagnosis and therapy and processes for the production of these compounds and agents.
The use of complexing agents or complexes or their salts in medicine has been known for a long time. The following are examples:
Complexing agents as stabilizers of pharmaceutical preparations, complexes and their salts as adjuvants for the administration of poorly soluble ions (e.g., iron), complexing agents and complexes (preferably calcium or zinc), optionally as salts with inorganic and/or organic bases, as a poison antidote in the case of inadvertent incorporation of heavy metals or their radioactive isotopes and complexing agents as adjuvants in nuclear medicine using radioactive isotopes such as .sup.99m Tc for radionuclide imaging are known.
In patents EP 71564, EP 130934 and DE-OS 3401052, recently complexes and complex salts have been presented as diagnostic agents, primarily as NMR diagnostic agents.
These complexes and complex salts are tolerated quite well and guarantee as complete an excretion of the ions as possible. But they still do not optimally fulfill all criteria that determine the relative effectiveness of an NMR contrast medium, of which mainly the following are to be named:
a strong NMR activity (relaxivity), so that the contrast medium, in as low concentrations as possible, lowers the relaxation times of the protons in the tissue fluid and other nuclei such as P, F and Na in vivo and thus makes possible the localization of tumors by increasing the signal intensity of the image obtained with the aid of nuclear magnetic tomography; as selective as possible a concentration and/or retention of the contrast medium at the target organ or cancerous tissue; sufficient water solubility; low toxicity; good tolerability; good chemical and biochemical stability.
Here, relevant for the image production are above all both the first-mentioned points. Since the relaxations times among the tissues differ at most only by a factor of 2-3 (T. E. Budinger and P. C. Lauterbur, Sciences 226, pp 288-298, 1984;), J. M. S. Hutchinson and F. W. Smith in Nuclear Magnetic Resonance Imaging Edit. C. L. Partain et al., pp 231-249, Saunders, N.Y. 1983) and the complexes and complex salts of the patents mentioned generally are flawed by the drawback that they distribute themselves only relatively unspecifically in the extracellular space and thus are not always suitable for a recognition of pathologically changed tissues, there exists a need above all for selectively bonding, tumor-specific compounds that can be used in diagnosis.
Now it has been known for a few years that porphyrin derivatives concentrate selectively in human and animal tumors (D. Kessel and T.-H. Chou, Cancer Res. 43, pp 1994-1999, 1983, P. Hambright, Bioinorg. Chem. 5, pp. 87-92, 1975; R. Lipson et al., Cancer 20, pp. 2250-2267, 1957, D. Sanderson et al., Cancer 30, pp 1368-1372, 1972). The first attempts to use this class of compounds also as diagnostic agents have also been described (J. Winkelmann et al., Cancer Research 27, pp 2060-2064, 1967; European patent application publication number 133603; N. J. Patronas et al., Cancer Treatment Reports 70, pp 391-395, 1986). With these compounds (tetrakis(4-sulfonatophenyl)- and tetrakis(4-carboxylatophenyl)-porphyrin), only the manganese(III) ion has proven suitable as a paramagnetic metal.
But the compounds previously described are far from satisfactorily fulfilling the criteria mentioned above; particular attention is still to be paid to their insufficient concentration in the target organs. An improvement of this property at the same time should help reduce the existing problems with toxicity and tolerability of the previously known compounds.
Therefore there continues to be a need, for many purposes, for complex compounds that are stable, easily soluble but also better tolerated, selectively bonding, easily accessible, have available a wider range of chemical variations of substituents (which, e.g., make possible the incorporation of metals other than manganese or several, also different, metals and thus simultaneously lead to a control of the properties and uses of the compounds) and that are suited for diagnosis and/or also therapy of tumors.

Mesotetraphenylporphyrin complex compounds, process for their production and pharmaceutical agents containing them


A method of chemical analysis that includes: a) introducing an analyte fluid having a flow to a surface of a sample chip through a microfluidic device comprising i) a fluid inlet having a semi-circular groove and ii) a flow chamber comprising an inner wall having an inlet end, where the fluid inlet is in communication with the flow chamber and where the inner wall at the inlet end is curved and has a radius similar to the radius of semi-circular groove; b) maintaining the flow of the analyte fluid such that the analyte fluid forms a pattern on the surface of the sample chip, the pattern approximating the semi-circular groove; c) maintaining the flow of the analyte fluid so that a linear fluid front forms on the surface of the sample chip at the inlet end; and d) maintaining the flow so that the linear fluid front moves along the surface of the sample chip.

Microfluidic flow cells that are used in, for example, microarray chemical analysis typically have small holes for fluid inlet and outlet. When the microarray area covers a large area, such as in high throughput analysis, the flow becomes localized between the fluid inlet and outlet, which results in high non-uniformity of the analyte across the surface of the microarray. To help alleviate this problem, a higher flow rate for the analyte fluid may be used to exchange the fluid in the flow cell; however, such high flow rates are undesirable because the analyte is often precious and may be present at low concentration.

Method for uniform analyte fluid delivery to microarrays


To provide a storage system capable of minimizing a performance deterioration, saving power consumption, and realizing a high reliability. A storage system according to the present invention includes a computer, a storage apparatus 1 connected with the computer, and a storage management apparatus connected to the storage apparatus, the storage apparatus including a hard disk unit to control a data write operation and a data read operation between the computer and the hard disk unit, and control on/off states of power supply of the hard disk unit on a group basis, and the system management apparatus collecting running information about the computer and computer execution job information for each computer, and determining an on/off time of the power supply of the hard disk unit on the group basis to record the collected information and the on/off time of the power supply on the group basis.

1. Field of the Invention
The present invention relates to a storage apparatus system (hereinafter also referred to as a "storage system") for storing data of a computer (hereinafter also referred to as a "server"). In particular, the present invention relates to a storage apparatus composed of a plurality of hard disk units and a technique of controlling a power supply of the plurality of hard disk units.
2. Description of the Related Art
In recent years, various kinds of companies have found it necessary to save all business documents or electronic mail in a storage system under various laws and regulations, and in addition, to enable prompt accesses to the stored data as needed.
A tape device that has been hitherto used as data storing means for storing a large volume of data no longer satisfies a desire to allow prompt accesses to the stored data. Meanwhile, the tape device encounters a problem in that high fault rates occur and there is a significant risk that data is lost or stolen during the conveyance of a tape medium.
On the other hand, a hard disk having a SATA (serial advanced technology attachment) interface has been put into widespread use as a hard disk for a laptop personal computer, which is noted as an inexpensive hard disk compared to a hard disk using a fibre channel interface. Such a hard disk is loaded in place of the hard disk using the fibre channel interface as a recording medium of the storage system, so a low-cost large-capacity storage system can be provided.
With this as a backdrop, a large-capacity storage system equipped with several hundreds to one thousand SATA hard disk units has come into widespread use as the large-capacity data storage means in place of the tape device.
However, the large-capacity storage system that has come into widespread use instead of the tape device is inferior to the tape device in power consumption. The power saving of the apparatus leads to reduction in operating cost of the entire system, resulting in reduction of TCO (total cost of ownership) of the entire system. Some recent reports reveal that the storage system consumes about 20 to 30% of the power in a data center, so how to save the power used for the apparatus becomes one of the biggest challenges for the future.
As a method for solving the above problems, Japanese Unexamined Patent Application Publication No. Hei 09-282057 discloses a technique of controlling on/off states of a power supply of an apparatus. This technique controls the on/off states of the power supply of a peripheral device connected to a computer on the basis of the plan to execute a job on the computer and the way to execute the job.
Further, as another method for solving the above problems, US Patent No. 20040054939 and Japanese Unexamined Patent Application Publication No. 2000-293314 disclose a technique of controlling on/off states of a power supply of a hard disk loaded in a storage system. The technique of US Patent No. 20040054939 controls the power supply on the basis of hard disk in a hard disk group constituting a RAID. Further, in a product manufactured with this technique, the number of hard disks running at a time is reduced to ¼ or less of the loaded hard disks (see http://www.copansys.com/pdfs/Revolution2000TDataSheet.pdf). The technique of Japanese Patent Application Laid-open No. 2000-293314 turns off or saves the power of a power supply of a hard disk of a hard disk group constituting a RAID, which is not accessed.
As the power saving method for the storage system, the related art of Japanese Unexamined Patent Application Publication No. Hei 09-282057 only controls the on/off states of the power supply of the entire apparatus, and there is no description about details of the power supply control such as the on/off control of the power supply of the individual hard disks loaded in the apparatus. This leads to a problem in that it is difficult to respond to an access request from a computer without delay and a power-saving effect is not so large. There is no description about how to prevent the loss of reliability of the individual hard disks due to the repeated on/off operations of the power supply.
The related art of US Patent No. 20040054939 (see http://www.copansys.com/pdfs/Revolution2000TDataSheet.pdf) has a problem in that even when the requisite number of operating hard disks is less than ¼ of the loaded hard disks, it is impossible to expect a power-saving effect as high as an effect attained when the number of operating hard disks is far less than ¼ of the loaded hard disks. In addition, several hard disks that always operate are provided for responding to the access request without delay, resulting in the increase in power consumption.
The related art of Japanese Unexamined Patent Application Publication No. 2000-293314 is such a passive power supply controlling method that the power supply of the hard disk is turned off when there is no access. Hence, it is difficult to respond to the access request without delay. There is no description about how to prevent the loss of reliability of the individual hard disks due to the repeated on/off operations of the power supply.

Computer apparatus, storage apparatus, system management apparatus, and hard disk unit power supply controlling method


Various embodiments of a system and method for optimizing storage library operations. In one embodiment a method may comprise storing a plurality of efficiency values indicative of relative efficiencies of storage targets in a storage library, and executing a storage library operation based on the plurality of efficiency values. Efficiency values may include, for example, information on a physical layout of the storage library. In one embodiment storage targets may include at least the following classes: a slot class, a portal class, a drive class, a picker class, and a media class. In one embodiment, executing a storage library operation based on the plurality of efficiency values may comprise selecting one or more storage targets to implement the storage library operation based on the plurality of efficiency values. For example, a drive closest to a given media unit may be selected to read the media unit.

1. Field of the Invention
This invention relates to the field of computer processing and, more particularly, to data storage libraries.
2. Description of the Related Art
Modern businesses increasingly own large numbers of computers, servers, and other information technology (IT) infrastructure, all of which may produce and process increasingly large amounts of data. In some instances the vast majority of this data may be discarded, but in other instances significant amounts of data must be stored and maintained in a storage library.
Storage libraries may be operable to store and retrieve storage media for reading and writing by an external computer system. Storage media may be tapes, discs, or other media which are typically operable to store tens of gigabytes or more per unit. Each storage media unit is typically stored within a slot, or storage area, and transported to and from a compatible media drive or access portal by a "picker". Sizes of storage media libraries may differ greatly, with some configurations holding only a handful of media units and a single drive, while others hold hundreds or thousands of media units and dozens of drives.
One or more external computers may be attached to the storage library by means of a network or data connection. These computers may be operable to access the media drives and to issue commands to move storage media units to and from various slots and drives via the picker, thereby giving any computer connected to the storage library the ability to access any media unit within the library at any time without human intervention.
A computer connected to the storage library may typically address storage targets such as slots, media units, drives, portals, and pickers within the library by a logical identifier. However, such logical identifiers typically give no indication as to the storage targets' relative spatial locality. For example, a computer may be unable to distinguish between a slot located close to a specific drive and a slot located far from the drive. Accordingly, an external computer is typically unable to lay out media in an efficient manner, which may in turn cause delays in retrieving and storing media units within the storage library.


Modified polyolefin fibers capable of easily producing a non-woven fabric having a high strength and a superior feeling, and provided with a broad range of processing temperature and further a low temperature adhesiveness and suitable to heating roll processing, and a non-woven fabric using the same are provided,. which fibers are obtained by adhering 0.1 to 1.0% by weight of an oiling agent composed mainly of a dibasic acid ester and/or a fatty acid ester, to polyolefin fibers having an index of birefringence of 0.054 or less, and which non-woven fabric has a strength of 0.85 or higher (Kg/5 cm) at 134.degree. C. and a processing temperature width of 132.degree. to 138.degree. C.

1. Field of the Invention
This invention relates to modified polyolefin fibers preferred as a raw material for a hot-melt-adhesive polyolefin non-woven fabric and the non-woven fabric. More particularly, it relates to modified polyolefin fibers having a superior card-passing through property at the time of processing a non-woven fabric, and a low temperature adhesion and a broad width of processing temperature, and also having superior working characteristics on heating rolls, and a non-woven fabric.
2. Description of the Related Art
Hot-melt-adhesive type non-woven fabrics have been broadly used in view of advantages of provisions, economy, hygienics, etc., because the fabrics do not require any binder. Among the fabrics, polyolefin non-woven fabrics are superior in the properties and economy; hence they have been used in many fields such as those of surface materials for paper diaper, goods for menses, etc., medical or hygienic materials for operating gown, etc., civil engineering materials, agricultural materials, industrial materials, etc., and conjugate fibers of polyethylene/polypropylene and single fibers of polypropylene, etc. have been used as raw material fibers therefor.
The method for processing hot-melt-adhesive non-woven fabrics is roughly classified into an air-through process using hot air and heating roll process. Among these, the air-through process is applied to polyethylene/polypropylene conjugate fibers. Non-woven fabric obtained according to the air-through process is strong and soft, but the processing speed is slower than that by means of heating roll process and the processing is inferior in the productivity. Further, since polyethylene/polypropylene conjugate fibers are used, there is a drawback of a waxy feeling specific of polyethylene.
On the other hand, heating roll process has a high processing speed and a high productivity, and hot-melt-adhesion is carried out; hence even when polypropylene single fibers are used, it is possible to make a non-woven fabric from the fibers, and there is an advantage that there is no waxy feeling due to polyethylene.
However, it has been regarded as difficult to produce a polypropylene non-woven fabric provided with both of strength and a soft feeling according to heating roll process. The reason is as follows:
In order to produce the polypropylene non-woven fabric by means of heating roll, it is necessary to improve the hot-melt-adhesion between polypropylene fibers, and it is therefor necessary to produce the non-woven fabric at a high temperature at which the polypropylene fibers sufficiently soften at the time of hot-melt-adhesion bonding thereof.
However, when the non-woven fabric is produced at such a high temperature, the hot-melt-adhesion bonded points are deformed into a film form, and the polypropylene fibers other than the bonded points are also affected by heat, so that the feeling becomes inferior. Further, when processing is carried out at a low temperature, hot-melt-adhesion at the bonded points is insufficient, and strength endurable to practical uses cannot be obtained. Thus, the range of production conditions under which a propylene non-woven fabric being strong and having a soft feeling can be obtained, is very narrow, so that there has been raised a problem of production that strength lowers due to a small change in the processing temperature and the feeling becomes hard. Thus, it has been awaited to develop polypropylene fibers having a broad processing temperature for obtaining a soft and strong polypropylene non-woven fabric, and suitable to heat-rolling process.
Japanese patent application laid-open No. Sho 62-156310 proposes, as polypropylene fibers suitable to heat-rolling process, polypropylene fibers composed of ethylene-propylene random copolymer containing a definite quantity of ethylene and having a softening point of 132.degree. C. or lower. However, the fibers have drawbacks that they have hard feeling and the processing temperature range wherein it is possible to produce a non-woven fabric provided with both of strength suitable to practical uses and feeling, is very narrow.
Further, Japanese patent application laid-open No. Hei 2-112456 discloses a non-woven fabric composed of fibers of polypropylene having a specified isotactic pentad fraction. This non-woven fabric has a good feeling, but its strength is insufficient. Further, in general, the fibers composed of such a low stereoregular polypropylene have inferior carding characteristics; hence the fibers have drawbacks such that a serious problem occurs in the intrinsic production of non-woven fabric.
Further, Japanese patent application laid-open No. Hei 2-264012 proposes polypropylene fibers having 1,3,5-trimethyl-2,4,6-trisbenzene and dimyristyl-3,3'-thiodipropionic acid ester blended therein, but the feeling and tenacity thereof are both insufficient.
Problem to be Solved by the Invention
As described above, a number of attempts to provide a polypropylene non-woven fabric having superior strength and feeling according to heating roll processing have been carried out, but the properties of the produced non-woven fabrics are insufficient, and the processing temperature range at the time of production thereof is narrow; thus, satisfactory polypropylene fibers have not yet been developed.
The present inventors have made strenuous research in order to solve the above problems, and as a result, have found that a product obtained by adhering an oiling agent composed mainly of a dibasic acid ester and/or a fatty acid ester onto polyolefin fibers of low orientation having an index of birefringence of 0.054 or less exhibits the aimed high strength of non-woven fabric and softness even within a low processing temperature range, and have completed the present invention.
As apparent from the foregoing, the object of the present invention is to provide superior polyolefin fibers capable of easily producing a soft and high feeling polyolefin non-woven fabric, and having a broad processing temperature range and being suitable to heating roll processing.

Modified polyolefin fibers and a non-woven fabric using the same