A method for separating hemoglobin A2 from a hemoglobin mixture according to a cation exchange liquid chromatography characterized that at least two types of eluents are used including an eluent (hereinafter referred to as xe2x80x9celuent Axe2x80x9d) for elution of faster hemoglobins than hemoglobin A0 and an eluent (hereinafter referred to as xe2x80x9celuent Bxe2x80x9d) for elution of hemoglobin A0 and slower hemoglobins than hemoglobin A0, and that the eluent A has a pH of 4.0-6.0 and the eluent B is maintained at a pH of at least 0.5 higher than that of the eluent A.

The present invention relates to a method for separating hemoglobin A2 by cation exchange liquid chromatography.
Hemoglobin A2 is composed of xcex1 and xcex4 chains, and is used, like hemoglobin F, as a diagnostic indicator of Mediterranean anemia (thalassemia). For testing of Mediterranean anemia, cation exchange liquid chromatography is generally employed to separate from a hemoglobin mixture and quantitate hemoglobin A2 (hereinafter referred to as HbA2).
Separation of a hemoglobin mixture, i.e., a hemolyzed sample, with the use of cation exchange liqud chromatography generally results in the appearance of peaks of hemoglobin A1a (hereinafter referred to as HbA1a ) and hemoglobin A1b (hereinafter referred to as HbA1b), hemoglobin F (hereinafter referred to as HbF), labile hemoglobin A1c, (hereinafter referred to as labile HbA1c), stable hemoglobin A1c (hereinafter referred to as stable HbA1c), hemoglobin A0 (hereinafter referred to as HbA0) and the like. On this occasion, an extended time has been required to achieve complete separation of HbA0 and HbA2 from each other since they show the similar retention behaviors with respect to a cation exchange column and their peaks occur in close proximity to each other.
One method of separating HbA2 from a hemoglobin (hereinafter referred to as Hb) mixture is disclosed, for example, in U.S. Pat. No. 4,810,391 which utilizes a weak cation exchange packing material and is characterized by the use of three types of buffering eluents having different phosphate concentrations and pH""s. A first eluent is a phosphate buffer maintained at a concentration of 1-20 mm and at a pH of 6.5-6.9 for use in elution of HbA1a and HbA1b. A second eluent is a phosphate buffer maintained at a concentration of 15-55 mM and at a pH of 6.4-6.8 for use in elution of HbA1c and HbA0. A third eluent is a phosphate buffer maintained at a concentration of 60-100 mM and at a pH of 6.4-6.8 for use in elution of HbA2.
EP-0315187 discloses a method for quantification of HbA2 wherein HbA1a and HbA1b are eluted by a first eluent, HbA1c and HbA0 by a second eluent and HbA2 by a third eluent.
However, in the above-described methods, the eluents are distinguished from each other substantially by the salt concentration only. This extends a measurement time and prevents quick separation and measurement of a lot of specimen, which have been problems. Another problem arises when HbA2 and HbA1c are concurrently separated and measured, i.e., precise measurement of HbA1c is disturbed significantly by the insufficient separation of HbA1cAlso, the pH""s of the eluents are lower than an isoelectric point of hemoglobin. This creates another problem, i.e., increases the tendency of Hb and other blood components to be adsorbed on packing material to thereby shorten a column service life.
In view of the above-described problems encountered in conventional methods of separating HbA2 from a Hb mixture, an object of the present invention is to provide a method which enables quicker and more precise separation of HbA2 than conventional methods.
A first invention of the present application is a method for separating hemoglobin A2 from a hemoglobin mixture by cation exchange chromatography, characterized in that at least two types of eluents are used including an eluent (eluent A) for elution of faster hemoglobins than hemoglobin A0 and an eluent (eluent B) for elution of hemoglobin A0 and slower hemoglobins than hemoglobin A0, and that the eluent A has a pH of 4.0-6.0 and the eluent B is maintained at a pH of at least 0.5 higher than that of the eluent A.
In a particular aspect of the first invention, the eluent B is maintained at a salt concentration lower than that of the eluent A.
In a more limited aspect of the first invention, an eluent (eluent D) is further used for elution of at least hemoglobin A2. The eluent D is maintained at a pH of at least 0.5 lower than that of the eluent B.
In a more limited aspect of the first invention, a salt concentration of the eluent B is rendered lower than that of the eluent A and a salt concentration of the eluent D is rendered higher than that of the eluent B.
In a further particular aspect of the first invention, an eluent (eluent C) is further used having an elution power weaker than those of the eluents B and D. Those eluents are delivered in the sequence of B, C and D.
In a further particular aspect of the first invention, an eluent (eluent H) at a pH of 6.8-12 is delivered to follow the eluent B, or alternatively, to follow the eluent D when the eluents B and D are used in combination. The eluent H preferably contains a chaotropic ion.
A second invention of the present application is a method for separating hemoglobin A2 from a hemoglobin mixture by cation exchange chromatography, characterized by the use of at least two types of eluents including an eluent (hereinafter referred to as xe2x80x9celuent Exe2x80x9d) which contains a chaotropic ion and also contains an inorganic acid, organic acid and/or any salt thereof having a buffer capacity at a pH of 4.0-6.8 and an eluent (hereinafter referred to as xe2x80x9celuent Fxe2x80x9d) which contains an inorganic acid, organic acid and/or any salt thereof having a buffer capacity at a pH of 6.5-8.0.
In a particular aspect of the second invention, an eluent (hereinafter referred to as xe2x80x9celuent Gxe2x80x9d) is further used having a lower pH and a higher salt concentration than the eluent F. The eluent G is delivered to follow the eluent F.
In a further aspect of the second invention, an eluent (eluent H) at a pH of 6.8-12 is delivered to follow the eluent F or G. Preferably, the eluent H contains a chaotropic ion.
In another particular aspect of the first or second invention, an azide ion is incorporated in at least one type of eluent and/or a hemolyzing solution.
In a further particular aspect of the first or second invention, a packing material is employed having at least one type of strong cation exchange group.
The first invention is now described.
In the first invention, xe2x80x9can eluent (referred to in this specification as xe2x80x9celuent Axe2x80x9d) used to elute faster hemoglobins than hemoglobin A0xe2x80x9d refers to the eluent used to elute Hb""s that exhibit shorter retention time than HbA0while the hemoglobin mixture is subjected to separation by cation exchange liquid chromatography. General examples of Hb""s to be eluted by the eluent A include HbA1a, HbA1b, HbF, labile HbA1c, stable HbA1c and the like. It should be understood that not all of the above-listed Hb""s but at least one type thereamong is needed to be eluted by the eluent A. The first invention, while its primary object is to separate HbA2, also enables the separation and quantitation of stable HbA1c by performing elution of HbA1a, HbA1b, HbF, labile HbA1c and stable HbA1c with the aid of the eluent A.
The eluent A has a pH of 4.0-6.0, preferably of 4.5-5.8. If a pH of the eluent A is below 4.0, denaturation of hemoglobin may be caused to occur. If a pH of the eluent A exceeds 6.0, hemoglobins may be charged less positively to reduce its tendency to be retained by the cation exchange group, resulting in its reduced resolution. The eluent A is not necessarily a single type of eluent, and may be an eluent group A consisting of plural types of eluents having differing compositions and elution powers (in the case where the eluent A consists of n types of eluents, they are hereafter designated xe2x80x9celuent A1, eluent A2, . . . , eluent Anxe2x80x9d), so long as the eluent group A satisfies the above-specified conditions required for the eluent A. When desired to separate and quantitate stable HbA1c, as well as HbA2, within a shorter period of time, the eluent components A1, A2, A3 and the like may be delivered in a sequence of increasing elution power according to a linear gradient elution technique, a stepwise gradient elution technique or a combination thereof.
In the first invention, xe2x80x9can eluent (referred to in this specification as the xe2x80x9celuent Bxe2x80x9d) used to elute hemoglobin A0 and slower hemoglobins than hemoglobin A0 xe2x80x9d refers to the eluent used to elute HbA0 and Hb""s that exhibit the same retention time or longer retention time than HbA0 while the hemoglobin mixture is subjected to separation by the cation exchange liquid chromatography. General examples of Hb""s to be eluted by the eluent B include HbA0, HbA2, HbS, HbC and the like. It should be understood here that not all of the above-listed Hb""s is needed to be eluted by the eluent B. The first invention may employ the eluents A and B only. In such a case, the eluent B is used to elute HbA0, HbA2 and the like. In the below-described case where an eluent D is used to elute HbA2, the eluent B may be used to elute at least HbA0. The eluent B may further elute stable HbA1c and labile HbA1c, so long as the elution of at least HbA0 is assured. Particularly when quantitation of HbF and HbA2 only are effected, the elution of stable HbA1c by the eluent B permits quicker separation.
Characteristically, the pH of the eluent B is rendered higher than that of the eluent A by at least 0.5. This is because the pH of the eluent B, if rendered at least 0.5 higher than that of the eluent A, improves resolution of HbA0. and HbA2. More preferably, the pH of the eluent B is rendered at least 0.8 higher than that of the eluent A. The pH of the eluent B is preferably in the range of 6.0-8.0, i.e., in the neighborhood of a hemoglobin""s isoelectric point (the Encyclopedia of Physics and Chemistry (4th ed., Iwanami Shoten, September 1987, edited by Ryogo Kubo et al.), at page 1178, describes the isoelectric point of hemoglobin as being pH 6.8-7.0). The eluent B is not necessarily a single type of eluent, and may be an eluent group B that consists of plural types of eluents having different compositions and elution powers (in the case where the eluent B consists of n types of eluents, they are hereafter designated xe2x80x9celuent B1, eluent B2, . . . , eluent Bnxe2x80x9d), so long as the eluent group B satisfies the above-specified conditions required for the eluent B.
In the first invention, a salt concentration of the eluent B is preferably made lower than that of the eluent A. The salt concentration of an eluent, as used herein, means a total concentration of cations present in the eluent. The salt concentration of the eluent B, if rendered lower than that of the eluent A, further improves resolution of HbA0 and HbA2. The salt concentration of the eluent B is preferably made lower than that of the eluent A by at least 10 mM, more preferably by at least 30 mM.
Other than the eluents A and B, an additional eluent (referred to in the present specification as xe2x80x9celuent Dxe2x80x9d) may preferably be used to elute at least hemoglobin A2. The use of this eluent D further improves the resolution between HbA2 and HbA0 and also between HbA2 and slower hemoglobins than HbA2. This eluent D suffices if effective to elute at least HbA2. Accordingly, in the case where the eluent D is effective to elute HbA2 only, HbS, HbC and the like may be eluted either by the eluent D or another eluent, for example, by an eluent H as will be described below.
Characteristically, the pH of the eluent D is rendered lower than that of the eluent B by at least 0.5. The pH of the eluent D, if rendered at least 0.5 lower than that of the eluent B, further improves the resolution between HbA2 and HbA0, and also between HbA2 and slower hemoglobins than HbA2. More preferably, the pH of the eluent D is rendered lower than that of the eluent B by at least 0.8. The eluent D is not necessarily a single type of eluent, and may be an eluent group D which consists of plural types of eluents having differing compositions and elution powers (in the case where the eluent D consists of n types of eluents, they are hereafter designated xe2x80x9celuent D1, eluent D2, . . . , eluent Dnxe2x80x9d), so long as the eluent group D satisfies the above-specified conditions required for the eluent D. The use of such an eluent group D not only permits precise separation of HbA2 within a short period of time, but also enables separation and quantitation of HbS, HbC and the like.
In the case where the eluent D is used, it is preferred that the eluent B is kept at a salt concentration lower than that of the eluent A and that the eluent D is kept at a salt concentration higher than that of the eluent B. Preferably, the eluent B is maintained at a salt concentration at least 10 mM lower than that of the eluent A while the eluent D is maintained at a salt concentration at least 10 mM higher than that of the eluent B. More preferably, the eluent B is maintained at a salt concentration at least 30 mM lower than that of the eluent A while the eluent D is maintained at a salt concentration at least 30 mM higher than that of the eluent B.
In the first invention, besides the eluents A, B and C, an additional eluent (referred to in this specification as xe2x80x9celuent Cxe2x80x9d) may further be used having a weaker elution power than the eluents B and D. In this case, those eluents can be delivered in the order of B, C and D. The use of such an eluent C retards elution of HbA2 so that the more precise separation of HbA2 can be achieved.
The eluent C may be maintained at any pH, so long as it has a weaker elution power than the eluents B and D. The eluent having a weak elution power, as used herein, refers to the eluent effective to retard elution of Hb""s when the hemoglobin mixture is subjected to separation by cation exchange liquid chromatography. An elution power of an eluent can be weakened by various techniques, including reduction of a pH or salt concentration of the eluent. In the present case, the eluent C is rendered lower than the eluents B and D, in terms of either or both of a pH and a salt concentraion.
In the first invention, the eluents are delivered in the order of A and B, or in the order of A, B and D if D is also used, or in the order of A, B, C and D if C is also used. In general, the elution power is controlled to increase in the order of A, B and D.
The above-described eluents A-D (hereinafter referred to as xe2x80x9celuentxe2x80x9d, collectively, in the description of the first invention), for use in the first invention, comprise a buffer. The buffer may be used in the form of containing suitable additives which will be described later. Examples of buffer agents contained in the buffer include inorganic acids, organic acids and salts thereof which are illustrated below.
Examples of inorganic acids include phosphoric acid, boric acid, carbonic acid and the like.
Examples of organic acids include carboxylic acids, dicarboxylic acids, carboxylic acid derivatives, hydroxy-carboxylic acids, amino acids, amines, imidazoles, pyridine, cacodylic acid, tris(hydroxymethyl)aminomethane, glycyl-glycine, pyrophosphoric acid and the like.
Examples of carboxylic acids include acetic acid, propionic acid and the like.
Examples of dicarboxylic acids include malonic acid, succinic acid, glutaric acid, adipic acid, maleic acid, fumaric acid, phthalic acid and the like.
Examples of carboxylic acid derivatives include xcex2,xcex2-dimethyl glutaric acid, barbituric acid, aminobutyric acid and the like.
Examples of hydroxycarboxylic acids include tartaric acid, citric acid, lactic acid and the like.
Examples of amino acids include aspartic acid, asparagine, glycine and the like.
Examples of amines include ethylenediamine, triethanol-amine and the like.
Examples of imidazoles include imidazole, 5(4)-methyl-imidazole, 2,5 (4)-dimethylimidazole and the like.
Examples of salts of inorganic or organic acids are known in the art, including sodium and potassium salts.
Examples of buffer agents include 2-(N-morpholino) ethanesulfonic acid (MES), N-2-hydroxyethylpiperazine-Nxe2x80x2-2-ethanesulfonic acid (HEPES), bis(2-hydroxyethyl)iminotris-(hydoxylmethyl)methane (Bistris), Tris, ADA, PIPES, Bistris-propane, ACES, MOPS, BES, TES, HEPES, HEPPS, Tricine, Bicine, glycylglycine, TAPS, CAPS and the like, which generally constitute a Good""s buffer. Other useful buffers include Britton and Robinson""s buffer and GTA buffer.
The above-listed inorganic acids, organic acids and their salts may be used alone or in combination. Also, the above-listed inorganic acids and organic acids may be used in combination.
The concentration of the buffer agent in the eluent is not particularly specified, so long as its buffer action is effective in water. It is preferably in the range of 0.1-1,000 mM, more preferably in the range of 1-500 mM.
The eluent may also contain (1) an inorganic salt, (2) a chaotropic ion, (3) a pH adjustor, (4) a water-soluble organic solvent and the like, which are listed below.
(1) Inorganic salt: Examples of inorganic salts include sodium chloride, potassium chloride, sodium sulfate, potassium sulfate, sodium phosphate and the like. While not particularly limited, they may preferably be incorporated in the amount of 1-1,500 mM.
(2) Chaotropic ion: Specific examples of chaotropic ions are listed in the subsequent description of an eluent E for use in the second invention. The concentration of the chaotropic ion in the eluent is preferably in the range of 0.1 mM-3,000 mM, more preferably in the range of 1 mM-1,000 mM, most preferably in the range of 10 mM-500 mM.
(3) pH adjustor: Known acids or bases may be used as pH adjustors. Examples of acids include hydrochloric acid, phosphoric acid, nitric acid, sulfuric acid and the like. Examples of bases include sodium hydroxide, potassium hydroxide, lithium hydroxide, magnesium hydroxide, barium hydroxide, calcium hydroxide and the like. While not limiting, these acids or bases may preferably be added in concentrations of 0.001-500 mM.
(4) Water-soluble organic solvent: Examples thereof include methanol, ethanol, acetonitrile, acetone and the like. Although not limiting, these organic solvents may preferably be added in concentrations of 0-80 % by volume. Preferably, their concetrations are maintained at levels insufficient to cause deposition of the chaotropic ion, inorganic acid, organic acid or any salt thereof used.
The second invention is now described.
In the second invention, at least two types of eluents are utilized including an eluent (referred to in this specification as xe2x80x9celuent Exe2x80x9d) which contains a chaotropic ion and also contains an inorganic acid, an organic acid and/or any salt thereof having a buffer capacity at a pH of 4.0-6.8, and an eluent (referred to in this specification as xe2x80x9celuent Fxe2x80x9d) which contains an inorganic acid, an organic acid and/or any salt thereof having a buffer capacity at a pH of 6.5-8.0.
The eluent E contains a chaotropic ion. The chaotropic ion is produced via dissociation of compounds in an aqueous solution. It destroys a structure of water and suppresses the entropy reduction of water that occurs upon contact with a hydrophobic material. Examples of negative chaotropic ions include a tribromoacetate ion, trichloroacetate ion, thiocyanate ion, iodide ion, perchlorate ion, dichloro-acetate ion, nitrate ion, bromide ion, chloride ion, acetate ion and the like. Other examples are urea and the like. Examples of positive chaotropic ions include a barium ion, calcium ion, magnesium ion, lithium ion, cesium ion, potassium ion, guanidine ion and the like.
The use of the following chaotropic ions, among the above-listed ions, is preferred for their ability to improve separation precision; negative ions such as a tribromo-acetate ion, trichloroacetate ion, thiocyanate ion, iodide ion, perchlorate ion, dichloro-acetate ion, nitrate ion and bromide ion; and positive ions such as a barium ion, calcium ion, magnesium ion, lithium ion, cesium ion and guanidine ion. Particularly preferred are a tribromoacetate ion, trichloroacetate ion, iodide ion, thiocyanate ion, perchlorate ion, nitrate ion and guanidine ion.
The concentration of the chaotropic ion present in the eluent E is preferably in the range of 0.1 mM-3,000 mM, more preferably in the range of 1 mM-1,000 mM, and most preferably in the range of 10 mM-500 mM. If it is below 0.1 mM, a separating effect may be reduced to result in the poor measurement precision. If it exceeds 3,000 mM, the effect of separating hemoglobins shows no further improvement. The above-listed chaotropic ions may be used alone or in combination.
The eluent E further contains an inorganic acid, an organic acid and/or any salt thereof having a buffer capacity at a pH of 4.0-6.8. Any of those listed in the preceding first invention as buffer agents, if having a buffer capacity at a pH of 4.0-6.8, can be used for such an inorganic acid, an organic acid and/or any salt thereof.
The concentration of the buffer agent in the eluent E is adjusted such that it exhibits a sufficient buffer action in water to maintain the eluent at a pH of 4.0-6.8. It is preferably in the range of 1 mM-1,000 mM, more preferably in the range of 10 mM-500 mM.
The eluent E is maintained at a pH of 4.0-6.8, preferably of 4.5-5.8. If a pH of the eluent E is below 4.0, denaturation of hemoglobin may be caused to occur. If it exceeds 6.8, hemoglobins may be charged less positively to reduce their tendencies to be retained by the cation exchange group, resulting in the reduced resolution.
The eluent F contains an inorganic acid, an organic acid and/or any salt thereof having a buffer capacity at a pH of 6.5-8.0, which are illustrated below.
Examples of inorganic acids include phosphoric acid and boric acid. Examples of organic acids include dicarboxylic acids, hydroxycarboxylic acids, amino acids, imidazoles, amines, alcohols and the like.
Examples of dicarboxylic acids include maleic acid, malonic acid, succinic acid and the like. Examples of hydroxycarboxylic acids include citric acid and the like. Examples of amino acids include asparagine, histidine and the like. Examples of imidazoles include 5(4)-hydroxy-imidazole, imidazole, 5(4)-methylimidazole, 2,5(4)-dimethyl-imidazole and the like. Examples of amines include ethylenediamine, diethanolamine, ethanolamine and the like.
Examples of alcohols include 2-amino-2-methyl-1,3-propanediol, 2-amino-2-ethyl-1,3-propanediol and the like.
Also useful are 2,4,6-collidine, N-ethylmorpholine, morpholine, 4-aminopyridine, pyrophosphoric acid, cacodylic acid, 5,5-diethyl barbituric acid, xcex2, xcex2xe2x80x2-dimethyl glutaric acid, glycerol phosphate and the like.
A Good""s buffer is also useful, including MES, Bistris, ADA, PIPES, Bistris propane, ACES, BES, MOPS, TES, HEPES, HEPPS, Tris, Tricine, glycylglycine, Bicine, TAPS and the like, for example.
The salts of inorganic and organic acids are known in the art and include sodium salts, potassium salts and the like, for example.
The above-listed inorganic acids, organic acids and/or their salts may be used alone or in combincation. The above-listed inorganic and organic acids may be used in combination.
The concentration of the buffer agent in the eluent F is adjusted such that it exhibits a sufficient buffer action in water to maintain the eluent at a pH of 6.5-8.0. It is preferably in the range of 1 mM-1,000 mM, more preferably in the range of 10 mM-500 mM.
The eluent F is maintained at a pH of 6.5-8.0, preferably of 6.7-7.8. This is because separation of hemoglobin A2 becomes insufficient if the pH of the eluent F falls below 6.5 or exceeds 8.0.
Besides the eluents E and F, the second invention further uses an eluent (referred to in this specification as xe2x80x9celuent Gxe2x80x9d) which has a lower pH and a higher salt concentration than the eluent F. The eluent G may be delivered to follow the eluent F.
The eluent G is preferably maintained at a pH lower than that of the eluent F by 0.1-5.0, more preferably by 0.5-4.0, most preferably by 1.0-3.0. Unless the pH of the eluent G is rendered at least 0.1 lower than that of the eluent F, poor separation of hemoglobin A2 may result. Unless it is rendered at most 5.0 lower than that of the eluent F, denaturation of hemoglobin may be caused to occur, resulting in the poor hemoglobin measurement precision.
The eluent G is also maintained at a salt concentration higher than that of the eluent F. The salt concentration is represented in terms of a total concentration of cations present in each eluent. The eluent G is preferably maintained at a salt concentration higher than that of the eluent F by 0.5 mM-200 mM, more preferably by 1 mM-175 mM, most preferably by 5 mM-150 mM. Unless the salt concentration of the eluent G is rendered at least 0.5 mM higher than that of the eluent F, insufficient elution of hemoglobin A2 may result. Unless it is rendered at most 200 mM higher than that of the eluent F, poor separation of hemoglobin A2 may result.
The eluent G may contain, as a buffer agent, such an inorganic acid, organic acid and/or any salt thereof having a buffer capacity at a pH of 4.0-6.8 as incorporated in the eluent E. Preferably, a chaotropic ion may be added to the eluents F and G, as similar to the eluent E.
In the second invention, the eluent E, F or G may further contain (1) an inorganic salt, (2) a pH adjustor, (3) a water-soluble organic solvent, (4) a stabilizer, (5) amine, (6) a surfactant and the like, which are illustrated below.
Those additives described to be useful for the eluent in the first invention can also be used for (1) inorganic salt, (2) pH adjustor and (3) water-soluble organic solvent.
(4) Hemoglobin Stabilizer: Examples of stabilizers include chelating agents such as ethylenediaminetetraacetic acid (EDTA), and reducing agents/antioxidants such as glutathione.
(5) Amine: A primary purpose of amine addition is to suppress the nonspecific adsorption of hemoglobin. Useful amines are known in the art. The use of primary, secondary and tertiary amines having melecular weights of 20-500 is preferred.
(6) Surfactant: Examples of surfactants include nonionic, cationic and anionic surfactants. The use of the surfactant permits efficient hemolysis and is effective to clean a flow path through which a hemolyzed sample is passed during measurement such as by high-performance liquid chromatography (HPLC). Preferred among the above-listed surfactants are nonionic surfactants. Examples of nonionic surfactants include polyoxyethylenes (polyoxyethylene is hereinafter referred to as POE, and the number of moles of ethylene oxide added is represented by (n)), POE(7) decyl ether, POE(n) dodecyl ether, POE(10) tridecyl ether, POE(11) tetradecyl ether, POE(n) cetyl ether, POE(n) stearyl ether, POE(n) oleyl ether, POE(17) cetylstearyl ether, POE(n) octyl phenyl ether, POE(n) nonylphenyl ether, sorbitan mono-laurate, sorbitan monopalmitate, sorbitan monostearate, sorbitan monooleate, POE(n) sorbitan monolaurate, POE(n) sorbitan monopalmitate, POE(n) sorbitan monostearate, POE(n) sorbitan monooleate and the like.
The above-listed surfactants may be used alone or in combination. Preferably, these surfactants may be added in the amount of 0.01-10 % by weight.
The constitution common to the first and second inventions (hereinafter referred to as xe2x80x9cpresent inventionxe2x80x9d, collectively) is now described.
In the present invention, an eluent (referred to in this specification as eluent xe2x80x9cHxe2x80x9d) at a pH of 6.8-12 is preferably delivered for the primary purpose of cleaning a column. The pH of the eluent H is such specified because of the following reasons. If below 6.8, the eluent H while passed through the column may fail to reach a pH equal to an isoelectric point of hemoglobin, resulting in the failure to clean the column effectively. If above 12, decomposition of a packing material may be caused to occur. More preferably, the eluent H is maintained at a pH of 7.5-11. The pH range of 8.0-9.5 is particularly preferred. However, the pH of the eluent H may be permitted to exceed 12, in the case where measurement is unaffected by decomposition of a packing material.
The eluent H may comprise, for example, a buffer containing an inorganic acid or its salt such as phosphoric acid, boric acid and carbonic acid; hydroxycarboxylic acid such as citric acid; carboxylic acid derivative such as xcex2,xcex2-dimethylglutaric acid; dicarboxylic acid such as maleic acid; or an organic acid or its salt such as cacodylic acid.
Examples of buffers include 2-(N-morpholino) ethane-sulfonic acid (MES), N-2-hydroxyethylpiperazine-Nxe2x80x2-2-ethanesulfonic acid (HEPES), bis(2-hydroxyethyl) iminotris-(hydoxylmethyl)methane (Bistris), Tris, ADA, PIPES, Bistris-propane, ACES, MOPS, BES, TES, HEPES, HEPPS, Tricine, Bicine, glycylglycine, TAPS, CAPS and the like, which generally constitute a Good""s buffer. Other useful buffers include Britton and Robinson""s buffer and GTA buffer. Also useful are organic substances, including imidazoles such as imidazole; amines such as diethanolamine and triethanol-amine; amino acids such as glycine and the like. These inorganic acids, organic acids and their salts may be used in combination. Alternatively, such inorganic and organic acids may be used in combination.
The above-listed inorganic acids., organic acids and their salts may be incorporated in the eluent H within the concentration range that allows them to exhibit sufficient buffer actions in water to keep the eluent H at a pH of at least 6.8, i.e., preferably within the concentration range of 1 mM-1,000 mM, more preferably of 10 mM-500 mM.
Preferably, a chaotropic ion may preferably be added to the eluent H to achieve a more effective column cleaning. Useful chaotropic ions are listed above. The chaotropic ion concentration is preferably in the range of 1 mM-3,000 mm, more preferably in the range of 10 mM-1,000 mM, most preferably in the range of 50 mM-500 mM.
Like the above-described eluents E, F and G, the eluent H may further contain various additives, including, for example, (1) an inorganic salt, (2) a pH adjustor, (3) a water-soluble organic solvent, (4) a stabilizer, (5) amine, (6) a surfactant and the like.
In the first invention, in the case where the eluent H is used, the eluents may be delivered in the order of A, B and H, or in the order of A, B, D and H, or in the order of A, B, C, D and H. In the second invention, in the case where the eluent H is used, the eluents may be delivered in the order of E, F and H, or in the order of E, F, G and H.
Also in the present invention, it is more preferred that an azide ion be added to at least one eluent selected from the eluents A-H. This azide ion may be added to a hemolyzing solution. The azide ion may be added to either or both of the eluent and hemolyzing solution. The azide ion may be added in the form of its salt which dissociates in an aqueous solution to produce azide ions. Useful azide salts are known in the art. The use of sodium azide, barium azide or the like is preferred.
The azide ion concentration in the eluent or hemolysed solution is preferably in the range of 0.001-0.5 % by weight, more preferably in the range of 0.005-0.4 % by weight. If the concentration is below 0.001 % by weight, an effect of improving resolution can not be obtained. If it exceeds 0.5 % by weight, no further resolution improvement can not be expected.
A packing material, for use in the cation exchange liquid chromatography according to the present invention, comprises particles having at least one type of cation exchange group. Such particles can be prepared, for example, by introducing cation exchange groups into polymer particles.
Examples of cation exchange groups are known in the art, and include a carboxyl group, a sulfonic acid group, a phosphoric acid group and the like. Any combination of such cation exchange groups may be introduced.
Preferably, a packing material is utilized having at least one type of strong cation exchange group. This strong cation exchange group refers to a cation exchange group which exhibits an ion exchange action even in an eluent maintained at an approximate pH of 2-3, such as a sulfonic acid group among those listed above. The use of the packing material having at least one strong cation exchange group reduces an eluent pH to such a degree that allows hemoglobins to be charged more positively and increases their tendency to be retained by a column, resulting in the increased resolution.
The above-described particles have diameters preferably in the range of 0.1-20 xcexcm, more preferably in the range of 0.2-8 xcexcm. The particle size distribution is preferably 40% or less, more preferably 30% or less, when represented by a coeffeicient of variation (CV value)(=(a standard deviation of a particle size distibution)/(its arithmetic mean)xc3x97100 (%))
Examples of such polymer particles include inorganic particles such as silica and zirconia; natural polymer particles such as cellulose, polyamino acid and chitosan; synthetic polymer particles such as polystyrene and polyacrylate; and the like.
Preferably, the polymer particle constituents, other than the introduced cation exchange group, are relatively hydrophilic. In view of the resistance to pressure and swelling, those constituents preferably have higher crosslinking levels.
A cation exchange group can be introduced into polymer particles by any known technique. For example, a technique can be utilized which comprises, in sequence, preparing polymer paticles having functional groups (such as hydroxyl, amino, carboxyl and epoxy) and allowing the functional groups to undergo a chemical reaction so that cation exchange groups are introduced into the polymer particles.
Alternatively, a cation exchange packing material may be prepared by a technique that produces polymer particles via polymerization of a monomer having a cation exchange group. For example, a technique can be utilized which involves mixing a cation exchange group-containing monomer with a crosslinking monomer and allowing the mixture to polymerize in the presence of a polymerization initiator.
Another applicable technique encompasses mixing polymerizable ester containing a cation exchange group, such as methyl (meth)acrylate and ethyl (meth)acrylate, with a crosslinking monomer; allowing the mixture to polymerize in the presence of a polymerization initiator; and subjecting the resulting polymer particles to hydrolysis so that the ester is converted into a cation exchange group.
Japanese Patent Publication No. Hei 8-7197 discloses a further applicable technique which comprises, in sequence, preparing crosslinked polymer particles, adding thereto a cation exchange group-containing monomer, and allowing the monomer to polymerize in the vicinity of polymer particle surfaces.
The above-described packing material is packed into a column for use in the liquid chromatographic measurement. The column is preferably sized to have an inner diameter of 0.1-50 mm and a length of 1-300 mm. More preferably, it measures an inner diameter of 0.2-30 mm and a length of 5-200 mm. If the column measures below 0.1 mm in inner diameter and below 1 mm in length, poor operability and resolution results. On the other hand, if the column measures above 50 mm in internal diameter and above 300 mm in length, the increased amount of packing material is required. Poor resolution also results.
Although any known technique can be utilized for packing the material into a column, the use of a slurry packing technique is preferred. Illustrating a specific example, packing material particles are dispersed in a buffer, such as an eluent, to provide a slurry which is subsequently injected into a column as by a delivery pump.
The column can be formed from materials known in the art, including metals such as stainless steel, glasses, resins such as PEEK (polyether ether ketone), and the like. Preferably, a portion of the column, e.g., an inner surface, that contacts with packing materials may be covered with an inert material. Examples of such inert materials include PEEK, polyethylene, Teflon, titanium compounds, silicon compounds, silicone films.
The column may be used in combination with a filter or a prefilter at least surface of which is formed from an inert material. Examples of such inert materials include cellulose ester, cellulose acetate, cellulose triacetate, cellulose, cellulose nitrate, polytetrafluoroethylene, polyvinylidene difluoride, polysulfone, polyethylene, polyether ether ketone, polyether sulfone, polypropylene, nylon, polyvinylidene fluoride, glass materials, acrylic copolymers, oxide ceramics, carbide ceramics, nitride ceramics, silicide ceramics, boride ceramics, titanium and the like. These materials can be used in any suitable combination. In the case where stainless steel and other materials are used which are not inert in nature, a suitable technique may be utilized whereby they are covered with an inert material, or they are rendered inert as by a treatment with silicone, or they are blocked with a blocking agent such as bovine serum albumin, gelatin, casein, globulin or hemoglobin.
Liquid chromatography for use in the separation method of the present invention is known in the art, and generally employs a delivery pump, a sample injecting equipment (sampler), a column and a detector. Other suitable auxiliary equipments (such as a column oven and an eluent degasser) may also be attached.
In the present invention, for liquid chromatography, a semimicro system can be used including liquid contacting parts, e.g., a pump, a mixing column, a sampler, pipings, a prefilter (holder, filter), a column and a detector (cell), which are reduced in dead volume to the minimum. The mixing column is preferably reduced in size to less than 500 xcexcl, more preferably to less than 250 xcexcl. An injection valve for the sampler is preferably reduced in volume to less than 10 xcexcl, more preferably to less than 5 xcexcl, most preferably to less than 2 xcexcl. An inner diameter of the piping is preferably reduced to less than 0.25 mm, more preferably to less than 0.13 mm, most preferably to less than 0.065 mm. In the case where the sampler, prefilter, column, detector and the like are connected by pipings, such pipings are preferably reduced in length to the minimum. The detector (cell) is preferably reduced in volume to less than 20 xcexcl, more preferably to less than 10 xcexcl, most preferably to less than 5 xcexcl The delivery pump preferably has the ability to supply a stable flow with least pulsation. More precise separation can be achieved within a short period of time when the liquid contacting parts are formed from inert materials, such as Teflon and PEEK, and an interior dead volume of the equipment is minimized.
An exemplary construction of the liquid chromatograph used to perform separation according to a stepwise gradient elution technique is shown in FIG. 1. Eluents a, b, c and d have differing elution powers. A solenoid valve 1 is opened at a specific time interval to allow deliver of each eluent. The eluent and a sample from a sample injection port 3 are fed together into a column 4 by the action of a delivery pump 2. Various components present in the sample are detected by a detector 5. An area, height and others of each peak are calculated by an integrator 6.
Other conditions for use in the separation method of the present invention are known in the art. Each eluent is preferably delivered at a flow rate of 0.05-5 ml/min, more preferably of 0.2-3 ml/min. In the case where the above-described semimicro equivalent system is used, each eluent is preferably delivered at a flow rate of 0.001-3 ml/min, more preferably of 0.01-1.8 ml/min, further preferably of 0.03-1 ml/min. It is difficult to stabilize the flow rate if slower than 0.001 ml/min. If the flow rate exceeds 3 ml/min, the separation precision may be lowered.
Various techniques, without limitation, can be utilized to deliver an eluent for use in the separation method of the present invention, including a linear gradient elution technique and a stepwise gradient elution technique, for example.
While not particularly limited, the detection of hemoglobins is preferably performed by a 415 nm visible light.
The hemoglobin mixture to be separated by the present method is generally prepared by diluting a hemolyzed solution obtained via hemolysis with a hemolytically active substance such as a surfactant. The amount of the hemoglobin mixture injected to the liquid chromatograph is varied depending upon the dilution ratio, but is preferably in the approximate range of 0.1-100 xcexcl.


The translator allows input of text entries into an input box and displays the translated text in an output box. The user enters text to be translated into an input box. The translator displays the translated text in the output box. The translator utilizes a dictionary to translate the entered text. The user may personalize the dictionary by adding, removing, and/or editing entries and dictionaries into a customizable dictionary. The user may add, remove, and/or edit entries and meanings of the dictionary. The user may also merge multiple dictionaries to create a single customized dictionary. The translator enables the user to save the dictionary for later use, delete a dictionary, and print a dictionary. The user may also send a dictionary to others to assist with translation.

I. Field of the Invention
The present invention relates to a translating interface that translates abbreviated text into words, phrases, and/or sentences. The present invention also translates words, phrases, and/or sentences into abbreviated text. The translator utilizes a dictionary to translate the abbreviated text into words, phrases, and/or sentences. The translator also utilizes a dictionary to translate the words, phrases, and/or sentences into abbreviated text. The user may personalize the dictionary by adding, editing, and/or removing entries, meanings, and dictionaries into a customizable dictionary. The user may also merge multiple dictionaries, entries, and meanings into a single dictionary to create a personalized dictionary.
The user adds, edits, and removes entries and meanings to create a customized dictionary. The user may also merge one or more dictionaries to create a single customized dictionary. The present invention also allows a user to create a customized dictionary by including entries and meanings selected by the user. The user may also save the dictionary for later use and send the dictionary to others so that others can translate the user's message.
Each dictionary customizes the translator for a particular user's needs. The dictionary may be customized to include terms related to a user's education, profession, field of interest, hobbies, or any other areas or topics for which a user may need a dictionary. For example, a law enforcement officer may require translation of drug slang language and/or other slang and acronyms into full words or vice versa. A user can add the slang and acronyms and their meanings to the dictionary for translations. The present invention also enables the user to print the dictionary to allow the user to review the dictionary to see entries and meanings to determine if the user needs to add, delete, and/or edit any entries and/or meanings. The user may also review the dictionary on the screen/display to determine if the user should add, delete, and/or edit any entries and/or meanings.
II. Description of the Known Art
Many students, professionals, and other people currently use computing devices such as lap tops, PDAs, mobile phones, or other computers for creating documents for record keeping, note taking, document production, text messaging, sending messages and/or electronic mail, and for producing other records. Such documents require a user to enter a set number of keystrokes to create the document. Because time is of the essence, users search for methods to reduce the time to create such documents.
Patents and patent applications disclosing information relevant are disclosed below. These patents and patent applications are hereby expressly incorporated by reference in their entirety.
U.S. Pat. No. 7,640,233 ("the '233 patent") issued to Baartman, et al. on Dec. 29, 2009 teaches electronic messaging systems, a machine-accessible medium, and methods for text-based electronic communication. In one embodiment taught by the '233 patent, a plurality of databases are provided. The databases taught by the '233 patent each define shorthand terms with one or more longhand terms. A shorthand term taught by the '233 patent is targeted within a text message, and the databases are searched for corresponding longhand terms. The '233 patent teaches that the longhand terms are selected for display according to factors such as user preferences, the identities of participants to the text communication, and the context of the text message. The '233 patent teaches that abbreviations, shorthand, and other jargon sent by one user is thereby interpreted. For example, one of the longhand terms taught by the '233 patent may be substituted in-line with the text message. Alternatively, all matches for the shorthand term found in the databases taught by the '233 patent may be listed in descending order according to relevancy.
U.S. Pat. No. 5,781,891 issued to Dvorak et al. on Jul. 14, 1998 teaches a simplified method of storing and invoking standard phrases during text entry to an electronic computer allows a phrase to be recalled by typing an abbreviated phrase name preceded by a predetermined character string selected from characters of a standard typewriter keyboard, eliminating the interruption typing often incident to finding special function keys. The character string is selected to be unambiguously distinguishable from standard entered text.
U.S. Pat. No. 5,761,689 issued to Rayson et al. on Jun. 2, 1998 discloses a method and word processing system for automatically replacing one or more characters of text entered by a user in a word processing document with the corresponding plain text, formatted text, or other object. The '689 patent discloses a method for automatically replacing an entry made by a user in a computer display with a replacement. The method begins with the step of enabling the user to indicate the entry that will be automatically replaced and then stores the indication. The user is also enabled to identify the replacement that will automatically replace the entry so that the identification of the replacement will be stored in relationship to the entry. Characters entered by the user are scanned to detect if the user has entered the characters comprising the entry, and to determine if a delimiter character was entered after the characters comprising the entry. The entry is automatically replaced with the replacement.
U.S. Pat. No. 4,893,238 issued to Venema teaches a text processing device for stenographic typing that comprises an alphanumerical keyboard, a translation device, a read/write memory and a display device. Given, frequently occurring words can be entered into the device in abbreviated form. Words of a main set are entered by way of a sequence of two or more key strokes. At least the first two thereof each define a word part to be separately pronounced, for example, in that they constitute the first letters of respective syllables. The full word corresponding to an abbreviated word is formed by the translation device in that at least one missing letter is inserted each time between two successively entered letters. By also providing one or more smaller auxiliary sets of abbreviations, there is an overall saving as regards the number of key strokes required to enter a text.
U.S. Pat. No. 5,623,406 issued to Ichbiah on Apr. 22, 1997 teaches a system for very fast entry of text into a computer. The system uses a current glossary, which may be custom generated to reflect common phrases and words pertaining to any specific subject matter, as a source for retrieving words and phrases from abbreviations. The '406 patent teaches multiple glossaries each of which is of interest to one of the system users. For instance, in a law firm there may be multiple lawyers who specialize in patent law, family law, and corporate law. Each group of lawyers would have their own glossary, or series of glossaries, which contain words and phrases which are commonly referenced in their specialty.
U.S. Pat. No. 6,915,138 issued to Kraft on Jul. 5, 2005 ("the '138 patent") teaches a message exchange handling concept. The '138 patent teaches that a user may according to this embodiment be offered an option to save the chat history as a text string so the text string may be used in another application, and e.g. forward it to a third person.
U.S. Publication No. 20090234876 ("the '876 publication") to Schigel on Sep. 17, 2009 teaches systems and methods to enhance relevancy efficiency of content sharing within a meta-community through content recommendation and recipient recommendation. The systems and methods taught by the '876 publication analyze sharing activities within the meta-community, both of members and of un-registered users through member sharing interactions, to create sharing preference profiles for members and un-registered users.
Certain problems exist with the aforesaid known art. The known art does not allow the flexibility and options provided by the present invention. The present invention provides a translator that decreases the amount of time required to enter text. The present invention improves the speed and increases the user's efficiency of entering text to increase the user's efficiency. The present invention also translates the abbreviated text into full words, phrases, and/or sentences to allow the user to easily read the entered text. The present invention translates the full words, phrases, and/or sentences to the abbreviated text. The abbreviated text allows a user to view the abbreviated message on a smaller display allowing the user to more easily read the full contents of the message. The present invention also allows the user to customize a dictionary according to the user's needs and/or preferences.
Therefore, the present invention is needed to provide a unique translator that enables a user to quickly enter text and provide a customized translation of the text to either abbreviate the message or to provide the message without the abbreviations depending on the user's desired output.


This invention provides a multilayer coating film-forming method by 2-coat-1-bake coating using a clear coat paint comprising a carboxyl group- and/or cyclic acid anhydride group-containing compound and polyepoxide, in which the coating workability and electrostatic coatability are improved by blending a specific organic solvent in the clear coat paint.

In top coat paint application onto automobiles, 2-coat-1-bake system has been widely used. This coating method comprises first applying a base coat paint to form a base coating film, applying onto the uncured base coating film a clear coat paint to form a clear coating film, and thereafter curing by heating the base coating film and clear coating film simultaneously. Thus obtained multilayer coating film excels in finished appearance such as gloss and depth.
Improvement in acid resistance of coating film has recently been in demand, and for meeting this demand, for example JP Hei 7 (1995)-133340A disclosed as a clear coat paint to be applied by 2-coat-1-bake system, a curable resin composition comprising polyepoxide, carboxyl group- and/or cyclic acid anhydride group-containing curing agent and a specific latent curing catalyst. Using this paint, coating film excelling in acid resistance can be obtained. When this clear coat paint is used in 2-coat-1-bake coating, however, there are such problems as that coating workability such as foaming resistance, sagging resistance and the like becomes insufficient in the occasions of thick textured coating, and that electrostatic coatability may become defective because high polarity of onium salt compound, which is among the latent curing catalyst used in the clear coat paint, lowers volume specific resistance of the paint.


An hybrid system (10) of the invention includes a fuel cell unit (20) that generates electricity upon being supplied with reaction gases, a secondary battery (40) that stores electric power generated by the fuel cell unit (20), and an electric power control device (30) that controls distribution of electric power supplied to electric power loads (M1, M2) from the fuel cell unit (20) and the secondary battery (40). The secondary battery (40) has a capacity characteristic of being able to supply the requested amounts of electric power of the electric power loads (M1, M2) at least during an early stage following restart of operation of the fuel cell unit (20) from a state of pause of operation.

A known electric power source installed in a fuel cell electric vehicle is a hybrid system in which a reformer, a fuel cell unit and a storage battery are installed. A hybrid system of this type is disclosed in, for example, Japanese Patent Application Laid-Open Publication No. 2000-315511 (JP-A-2000-315511). In a construction disclosed therein, electric power is distributed from the fuel cell unit or the storage battery, via an electric power regulator, to a vehicle-driving traction motor, and accessories of the fuel cell unit, and the reformer, in accordance with driver's operation of an accelerator. The storage battery capacity provided in the vehicle is set at an amount that, when the system is started, allows supply of electric power to the traction motor, the accessories of the fuel cell unit only from the storage battery during a period until the reformer is sufficiently warmed up and is able to stably supply a reformed gas to the fuel cell unit.
In a fuel cell electric vehicle having such a hybrid system, the response delay of the fuel cell unit (a time delay prior to performance of steady electricity generation) at the time of detection of a high load request during an intermittent operation mode becomes a problem. The intermittent operation mode refers to an operation mode in which during a low load condition, for example, during idling or deceleration or the like, the operation of the fuel cell unit is temporarily stopped, and the vehicle is driven only on the basis of the supply of electric power from the storage battery. If the intermittent operation duration (duration of pause of operation) of the fuel cell unit becomes long, there is possibility of deterioration of the I-V characteristic (electric current-to-voltage characteristic) of the fuel cell unit from the I-V characteristic occurring prior to the pause of the fuel cell unit. The I-V characteristic of the fuel cell unit fluctuates all the time depending on the cell temperature, the reaction gas flow, the gas pressure and the humidity, and also considerably fluctuates with fluctuations of the internal resistance of a polymer electrolyte membrane caused by changes in the water content as well as states of battery operation (an excessive state, a steady state, etc.). Once the I-V characteristic deteriorates, a restart of the fuel cell unit in response to a high load request does not immediately achieve a sufficient recovery of the cell voltage; specifically, a time of about 1 to 2 seconds is required for the recovery to a sufficient voltage. Besides the response delay of the fuel cell unit, the response delay of the entire fuel cell system, including the accessories thereof, is unignorable. If the response delay of the fuel cell unit becomes equal to or longer than 200 ms, remarkably degraded drivability results. Therefore, there is a strong demand for development of an improvement technology regarding the response delay of the fuel cell unit.
There is another problem to be solved. If the storage battery capacity provided in a fuel cell electric vehicle is insufficient, it becomes impossible to cope with a high load request. On the other hand, provision of an excessively large storage battery capacity is a waste of resources. Thus, there is a need to review the installation design so that a storage battery that accords with the vehicle characteristics will be selected.


A cationic composite filter aid may include a silicate substrate, a silica precipitated on the silicate substrate, and a cationic surface modification of the precipitated silica. A method for making a cationic composite filter aid may include providing a silicate substrate, precipitating a silica onto the silicate substrate to form a composite filter aid, and cationically modifying the precipitated silica to form a cationic composite filter aid. A method for filtering a liquid may include providing a liquid for filtering and filtering the liquid through a cationically modified composite filter aid. The cationically modified composite filter aid may include a silicate substrate, a precipitated silica, and a cationic surface modification of the precipitated silica.

Silica filter aids can be used to filter liquids. However, silica and silicate filter aids have negatively-charged surface characteristics. The negative charge may make these types of filter aids suitable for filtering positively-charged ions and molecules, but they may be poor filtration elements for negatively-charged ions and molecules. Negatively charged ions and molecules, such as arsenic, can have adverse effects or possess undesirable health properties if not properly filtered. Such particles can also lead to undesirable liquid properties, such as discoloration or oxidation.
Thus, it may be desirable to provide a filter aid composition with improved ability to remove negatively charged particles from a liquid. It may also be desirable to provide a filter aid having adsorption properties with improved filtration rates. It may also be desirable to provide a method of making a filter aid composition for filtering negatively-charged impurities.


Various embodiments include engine carburetors. Various embodiments provide for methods of cylinder manufacturing engines. Various embodiments provide for methods of cylinder manufacturing four-stroke engines. Various embodiments provide for methods of cylinder manufacturing two-stroke engines.

Conventional four-stroke engines have certain disadvantages as they are complicated and difficult to manufacture and assemble because there are numerous parts as compared to two-stroke engines. The additional parts, for example include, valve trains consisting of intake and exhaust valves, followers in the case of push tube trains for transmitting motion from cam lobes to rockers, just rockers in the case of overhead cam and belt or chain drives for overhead cam types. Also included are cam gear or pulley as the case may be, valve springs and retainers, camshafts, and cam covers in some cases. Also, the method of assembling the main components varies depending on how the cylinder, crankcase, crankcase cover, piston rod and crankshaft assemblies are made. Also, in the conventional hand held four-stroke engines, the oil is either recirculated in a wet type lubrication or pre-mixed with fuel for mist lubrication.
It is known in the prior art that four-stroke engines have cylinder blocks (with or without a separate cylinder head) and crankcases as the case may be with or without crankcase covers. For example, cylinders manufactured by MTD Southwest has a cylinder head integral with the cylinder and has a separate crankcase which has main bearings to support the crankshaft and a separate volute attached to the crankcase. The volute also has bosses for the ignition module. Another example is a Honda engine which has a cylinder block including a cylinder, where the upper half of the crankcase is integral with the cylinder block and a lower half of the crankcase which, when assembled together, support the main bearings. In this case, there is no separate crankcase cover and the belt drive for the overhead valve system is a wet type, where the upper and lower half of the crankcases together form a reservoir for the lubricating oil and the belt is completely enclosed. The enclosure is integral with the upper half of the crankcase. A similar design is used for a push tube type of valve train. Reference may be made to U.S. Pat. Nos. 6,539,904, 6,672,273, 6,427,672, 6,508,224, 6,705,263 (belt drive), and U.S. Pat. No. 6,021,766 (push tube).
Some Honda full crank engines have the crankcases split at an angle to the crankshaft as disclosed in U.S. Pat. Nos. 6,250,273 and 6,644,290. The front half of the crankcase is integral with the cylinder block and has bearing boss to support the front half of the crankshaft and the rear half of the crankcase has another bearing boss to support the outboard side of the crankshaft. The cam gear or the pulley for transmitting the motion to the overhead valves is in the outboard side.
Another example of engines with push tubes are disclosed in U.S. Pat. Nos. 6,213,079, 7,243,632, and 6,119,648. Some engines use gears to transmit rotation from crankshaft to the overhead camshaft, which is running at half the crankshaft speed as disclosed in U.S. Pat. No. 6,152,098. In most cases where the engine has a two piece block, the top or front half and lower or outboard half of the crankcase, the valve train is on the outboard side.
In the case of upper and lower halves of crankcases (or left and right halves as in Kioritz U.S. Pat. No. 6,119,648, the disadvantages are that the upper and lower halves are first assembled together and then the bearing bores are machined. They are taken apart for the final assembly. They are not interchangeable. A sealing gasket is used to seal the two halves. As such, the cost of such a system is higher than the one proposed in the design disclosed herein.
Prior art disclosed in U.S. Pat. No. 2,287,508 refers to a wet lubrication, where the oil is pumped into various sections of the engine and oil is recirculated. The lubricating pump is not described clearly, but it is driven by the camshaft. In the handheld trimmer sold by Mitsubishi model TL 26, the oil pump is driven by the crankshaft on the outboard side, but it is two-stroke engine and 100% of the air-fuel mixture enters the crankcase chamber.
Thus, engine designers are constantly trying to design engines that have less parts, are simpler, and less expensive to manufacture.
Disadvantage with conventional four stroke engines for hand held application is that the oil in the crankcase may seep into the combustion chamber and cylinder head when the equipment is turned upside down.
In some hand held engines, such as trimmers and blowers, the location and size of the fuel tank is constrained by the size of the engine and the shape and size of the crankcase cover. The constraint is more when the fuel is propane gas. Propane gas are typically made out of metal and preferably of cylindrical shape. Therefore the height of the whole engine is significantly higher when propane tank is mounted either on the top or bottom of the engine. The embodiments disclosed here provide many advantages over the prior arts.
In some electronic fuel injection system, the fuel is gasoline or diesel. However, in small hand-held engines, electronic fuel injection system is complex as it requires a separate fuel pump, either integral with the throttle body or a separate system. In either case, the cost of the system becomes expensive because of the additional parts.
The embodiment described here does not require a pump, as the fuel is already at a pressure in the LPG fuel tank or even in a compressed natural gas tank. The advantage described in this embodiment is that the throttle body can be integral with the pressure regulator and a metering chamber if necessary. It is also possible to have a pressure regulator only either integral with the throttle body or a separate pressure regulator commonly used with LPG tanks.


The present disclosure relates to a curable system comprising at least two compositions (A) and (B) where composition (A) comprises an epoxy resin, an inorganic thixotropic agent, an organic gelling agent and a filler and composition (B) comprises a hardener, an inorganic thixotropic agent, an organic thixotropic agent and filler. The curable system may be used in the manufacture of components or parts of electrical equipment.

A typical process for making cast resin epoxy insulators is the automatic pressure gelation process (APG process). The APG process requires that before injecting the reactive mixture into a hot mold the curable system comprising the epoxy resin composition (composition A) as well as the composition comprising the hardener for the epoxy resin (composition B) have to be prepared to be ready for injection.
In ease of pre-filled systems, i.e. a system having compositions which comprise a filler, the composition must be stirred up in the delivery container due to the sedimentation of the filler in the composition. Typically, in order to obtain a homogeneous formulation the filler containing composition has to be heated up and stirred. After homogenization of each composition of the curable system the compositions are combined and transferred into a mixer and mixed at elevated temperature and a reduced pressure in order to degas the formulation. The degassed mixture is subsequently injected into the hot mold.
In case of non-pre-filled systems the epoxy resin composition and the hardener composition are typically mixed individually with the filler and optionally further additives at elevated temperature and reduced pressure to prepare the pre-mixture for the resin and the hardener. In a further step the two compositions are combined to form the final reactive mixture, typically by mixing at elevated temperature and reduced pressure. Subsequently, the degassed mixture is injected into the mold.
However, the APG process known in the prior art requires several steps, i.e. at least a stirring step in order to avoid the sedimentation of the filler and additionally a degassing step.
In the field of silicone process technology curable systems are where two compositions are pumped at ambient temperature out of the respective delivery containers without degassing or prestirring through a static mixer into a mold. The mixing and dosing equipment is sufficient to fulfil the requirements to process the two compositions in order to prepare a reactive mixture which can be injected into a mold. Depending on the size of the article to be prepared the respective volume is injected through a static mixer into the mold.
The basic design of all silicone injection systems is composed of a base frame to hold the different compositions. The compositions can be stored in commercially available drums. A hydraulic control ensures a synchronous operation of the dosing pumps.
The existing curing systems cannot be applied to the "silicone processes".

Filled two-component curable epoxy system with enhanced sedimentation stability


An image forming apparatus includes an accumulating unit to accumulate documents, a document selecting unit to receive selection of the accumulated documents to be printed, a screen displaying unit to display on a display unit a printing condition setting screen including default values for selecting plural of the accumulated documents and a list of setting items when the selection received by the document selecting unit indicates plural of the accumulated documents, a reset receiving unit to receive selection of the setting item to be changed and resetting of a default value of the selected setting item, a reset control unit to change a content of the setting item into a resetting content when the setting item is resettable or allow the content to remain unchanged when the setting item is not resettable, and a printing unit to print the accumulated document, the setting item of which is reset.

1. Field of the Invention
The disclosures herein generally relate to an image forming apparatus and a non-transitory recording medium storing a program.
2. Description of the Related Art
It is generally performed that documents accumulated in a storage device are retrieved at a desired time to print out the retrieved documents. When printing such accumulated documents, it may be necessary to have a selecting operation to select one or more accumulated documents desired for printing and a printing condition setting operation to set printing conditions of the selected documents.
For example, Japanese Laid-open Patent Publication No. 2003-127473 (hereinafter referred to as "Patent Document 1") discloses a technology generally known in the art in which documents accumulated in a storage device are retrieved for printing at a desired time. More specifically, Patent Document 1 discloses an image forming apparatus capable of retrieving document data to be printed at a desired time. The disclosed image forming apparatus includes a data storage unit to accumulate the document data, a printed history recording unit to record a history of the printed document data and a bibliographic information recording unit to record a recognition code for specifying the document data and bibliographic information. In the image forming apparatus disclosed in Patent Document 1, document selection and printing conditions may be set based on the printed history information at a desired position acquired from the printed history information recorded by the printed history recording unit.

Image forming apparatus and recording medium


A charge transport composition is provided including a cyclo-aliphatic ether compound. One purpose of the cyclo-aliphatic ether compound is to improve the resistance to crazing, crystallization and etching of the charge transport layer. The charge transport composition may be coated along with a charge generation composition onto a conductive substrate to form a photoconductor. The charge transport composition may therefore be employed in a photoconductor located in a printer or a printer cartridge.

1. Field of Invention
The present invention relates to a charge transport formulation and photoconductors having improved crazing/cracking or crystallization resistance. In particular, the present invention relates to a charge transport formulation suitable for use in a photoconductor containing a cyclo-aliphatic compound to reduce printing defects.
2. Description of the Related Art
Organic photoconductors may incorporate a laminate structure including a charge generation layer (CGL) and a charge transport layer (CTL) coated over a conductive substrate. A charge generation layer may include a pigment dispersed in one or more types of binders. A charge transport layer, which may be the outer layer, may include one or more charge transport compounds and a binder.
In some instances, it is preferable that the surface of the photoconductor be relatively smooth and free of any defects that may occur in the laminate structure, and particularly in the charge transport layer, including cracking, crazing, or crystallization of the charge transport molecules. Such photoconductor defects may lead to image defects and increased residual discharge. One Japanese reference to Nomori et. al and purportedly assigned to Konsihiroku Photo Industry Company, Ltd, Japan (with other specific details apparently lost) describes the use of an n-propylcarbazole as a plasticizer to help prevent crack formation.

Control of crazing, cracking or crystallization of a charge transport layer in a photoconductor


A device for discriminating valuable papers comprises a battery 1; a self-holding circuit 5 connected between battery 1 and drive controller 2 and capable of being switched between an active condition for supplying electric power to validation sensor 4 and drive controller 2 from battery 1 and an inactive condition for interrupting the power supply; a trigger element 6 for switching self-holding circuit 5 in the inactive condition to the active condition; and a shutoff circuit 7 having a control terminal connected to drive controller 2 for switching self-holding circuit 5 in the active condition to the inactive condition. Inactive condition of self-holding circuit 5 during the disuse period, saves electric power to extend service life and exchange cycle of battery 1.

Prior art bill validators have been used for various kinds of bill handling machines such as vending machines, money exchangers and bill dispensers installed all over the world. As shown in FIG. 12, a prior art bill validator comprises a conveyer 3 for transporting a bill inserted from an inlet 33 along a passageway 34 to a stand-by position 36; an inlet sensor 30 mounted at a front end of passageway 34 for detecting bill inserted into inlet 33; a validation sensor 4 for detecting optical or magnetic pattern of bill moving through passageway 34 to produce detection signals; a stacking device 41 for stowing bill moved to the stand-by position 36 into an accumulation chamber 44; and a drive controller 2 for receiving detection signals from validation sensor 4, validating authenticity of bill and providing conveyer 3 and stacking device 41 with drive signals. Validation sensor 4 includes a magnetic sensor 22 such as magnetic head or Hall element for discerning magnetic characteristics on bill transported along passageway 34, and an optical sensor 21 such as photo-coupler for discerning optical characteristics on or through bill. Drive controller 2 receives detection signals from validation sensor 4 and examines authenticity of bill and decides a genuine or false bill based on the received detection signals. Passageway 34 includes a generally horizontal validation path 34a connected to inlet 33 at one end thereof; an arcuate path 35 having an upper end connected to the opposite end of validation path 34a from inlet 33; and the stand-by position 36 connected to a lower end of arcuate path 35. Arcuate path 35 serves to divert passageway 34 substantially an angle of 180 degrees to transport bill to stand-by position 36 positioned under and in parallel to validation path 34a.
As shown in FIGS. 12 and 13, a convey stacker 43 comprises a convey motor 25; a pinion 70 mounted on an output shaft of convey motor 25; a first gear 71 in mesh with pinion 70; a second gear 72 mounted on a common rotation shaft for first gear 71; a third gear 73 engaged with second gear 72; a fourth gear 74 mounted on a common rotation shaft for third gear 73; a fifth gear 75 mating with fourth gear 74; a sixth gear 76 mounted on a common rotation shaft for fifth gear 75; a seventh gear 77 in engagement with sixth gear 76; a eighth gear 78 mounted on a common rotation shaft for seventh gear 77; a ninth gear 79 interlocking with eighth gear 78; a tenth gear 80 mounted on a common rotation shaft for ninth gear 79; and a eleventh gear 81 meshing with tenth gear 80. Eleventh gear 81 is mounted on a common rotation shaft for a convey roller 32 which is rotatable along arcuate path 35. As shown in FIG. 13, two rubber rings 32a are wound in parallel to each other around an outer cylindrical surface of convey roller 32 to transmit rotational force to bill through rubber rings 32a in order to smoothly convey bill along arcuate path 35.
As shown in FIG. 15, eleventh gear 81 is provided with a drive belt pulley 84, and a drive belt 83 is wound around drive belt pulley 84 and some idle belt pulleys. A driven belt pulley 84 is mounted on a common rotation shaft for a convey belt pulley 26 around which a belt 27 is wound.
As shown in FIG. 14, attached to tenth gear 80 is a crank plate 55 which supports a pin 56 secured in an eccentric position on crank plate 55 to rotatably connect one end of a connecting rod 57 to pin 56. The other end of connecting rod 57 is rotatably connected to a shaft 59 located in an elongated opening 58 formed on frame wall; shaft 59 is rotatably received in a hole formed at an end of a first link 60; and the other end of first link 60 is pivotally connected to a push plate 40 through a pin 61. A pin 62 rotatably connects each intermediate portion of first and second links 60 and 63; one end of second link 63 is rotatably attached to frame wall by a pin 64; the other end of second link 63 is rotatably and slidably attached to push plate 40. With rotation of crank plate 55, the other end of connecting rod 57 performs reciprocal movement together with shaft 59 within elongated opening 58; reciprocal movement of shaft 59 causes telescopic movement of first and second links 60 and 63 to move push plate 40 toward and away from accumulation chamber 44 of stacking device 41. Convey motor 25 is electrically connected to drive controller 2 which rotates convey motor 25 in the adverse direction to rotate crank plate 55 when drive controller 2 decides bill as genuine, and rotation of crank plate 55 causes extension of first and second links 60 and 63 to move push plate 40 downward and stow bill by push plate 40 into accumulation chamber 44 of stacking device 41. Not shown but, as crank plate 55 is mounted on tenth gear 80 through a uni-directional or one-way clutch, it is not rotated during the forward rotation of convey motor 25. Accordingly, only when convey motor 25 is rotated in the adverse direction, crank plate 55 is rotated to move push plate 40 between the original or retracted and extended positions.
Bill is transported to the stand-by position 36, and a holder 47 retained in the horizontal condition serves to temporarily support a rear end of bill substantially in the horizontal condition as shown by solid line in FIG. 12. Then, bill in the stand-by position 36 is put into accumulation chamber 44 of stacking device 41 when push plate 40 is moved downward. At that time, holder 47 is rotated downward by a rear end of bill put into accumulation chamber 44 so that rear end of bill is curved or deflected to override holder 47 and move under holder 47. In this way, pushed bill certainly is moved under holder 47 not to prevent entry of a next bill to the stand-by position 36 by the sticking rear end of stacked bill and to avoid jamming of bill by the next bill. Rotatably mounted is a lever 46 which is resiliently urged and retained to the horizontal position by a spring 49 so that passage of bill causes lever 46 to rotate against resilient force of tension spring 49 and allow passage of bill. Provided under convey device 3 is stacking device 41 for storing bills to sandwich the stand-by position 36 between convey device 3 and stacking device 41.
In operation of the bill validator, when bill is inserted into inlet 33, inlet sensor 30 detects bill to produce a detection signal to the drive controller 2. Then, convey motor 25 is rotated in the forward direction to drive convey belt 27 through drive belt 83 so that bill is inwardly transported along validation path 34a. At this time, validation sensor 4 converts magnetic and optical feature of bill into electric signals to drive controller 2 which then examines and decides a genuine or false bill based on the received detection signals. When drive controller 2 does not decide bill as genuine, it provides convey motor 25 with inverted signals in the way of conveyance to drive convey belt 27 in the adverse direction and thereby return bill from validation path 34a to inlet 33. On the contrary, when drive controller 2 decides bill as genuine, it continuously rotates convey motor 25 in the forward direction to transport bill along arcuate path 35 to the stand-by position 36. At the moment, both sides of bill are supported on a pair of opposite side ribs 37 shown in FIG. 16, and rear end of bill is supported on holder 47, but push plate 40 is kept in the original position above the stand-by position 36. Then, drive controller 2 rotates convey motor 25 in the adverse direction to rotate crank plate 55. This causes first and second links 60 and 63 to extend as shown in FIG. 14 so that push plate 40 is moved into accumulation chamber 44 of stacking device 41 to stow bill retained in the stand-by position 36 in accumulation chamber 44 of stacking device 41. When push plate 40 crams bill through an opening 39 formed between side ribs 37 into accumulation chamber 44, holder 47 is rotated downward from the horizontal position to a certain angle against elastic force of tension spring 49. When bill overrides and moves away from holder 47, it is returned to the original horizontal position by elastic force of tension spring 48. Thereafter, when convey motor 25 is rotated in the adverse direction to rotate crank plate 55 an angle of nearly 360 degrees, first and second links 60 and 63 are retracted to return push plate 40 from the stand-by position to the upper original position.
In this way, when bill in the stand-by position is squeezed downward into accumulation chamber 44, lever 46 is rotated downward by rear end of pushed bill, and rear end of bill is curved or deflected to pass over and move under lever 46. In that way, reliable stowage of pushed bill under lever 46 allows a next bill to smoothly enter the stand-by position 36 without barring entrance of subsequent bill into the stand-by position 36 by sticking out rear end of bill that results in jamming of the subsequent bill. FIG. 17 shows an appearance of the bill validator.
By the way, prior art bill validators are defective in consuming a large amount of electric power because they always require continuously running current even during the inoperative period of validators. Therefore, prior art bill validators are unavailable without commercial power supply. Otherwise, although batteries are provided in validators, more frequently batteries have to be exchanged for new ones or charged due to the large consumption power, and therefore, a bill validator of power saving type has still been required.
An object of the present invention is to provide a device for discriminating valuable papers capable of reducing power consumption by automatically switching it from the active to the inactive condition during the inoperative period.

Device for discriminating valuable papers with low power consumption


The cap (1) portion of the assembly comprises at least one guarantee strip (2, 3) connected to its body (5) by breakage bridges (4), the neck of the receptacle carrying ratchet teeth and the guarantee strip (2, 3) carrying internal teeth (6) adapted to cooperate with the ratchet teeth. The ratchet teeth (9) are elastically inclinable in the direction of screwing to allow the cap (1) to be screwed on while preventing its being unscrewed without breaking the bridges (4). At least one guarantee strip (2) has free ends (21) and is ejected transversely the first time the cap (1) is screwed on. The internal teeth (6) are so disposed that they cooperate with the ratchet teeth by only a single internal tooth (6) upon screwing and unscrewing. The cap (1) can be applied to tamper-proof receptacles in the cosmetic, pharmaceutical, hygiene, food and cleaning product industries.

U.S. Pat. No. 315,403 describes a screw closure cap of plastic material associated with a receptacle, the cap comprising a circular guarantee ring connected to the body of the capsule by breakable bridges. The neck of the receptacle carries profiled faces or "ratchet teeth", and the guarantee strip carries internal teeth co-operating with the ratchet teeth, latter being elastically inclinable in the direction of screwing in order to allow the cap to be screwed on without breaking the breakable but then preventing its being unscrewed without these bridges being broken, the ratchet teeth then being elastically straightened.

Assembly comprising a screw closure cap of plastic material with a guarantee strip and a receptacle, and the corresponding cap


Substituted phosphorothioate derivatives and pharmaceutical compositions thereof as potential antiradiation agents are disclosed.

1. Field of the Invention
The present invention relates to novel phosphorothioate compounds and pharmaceutical preparations thereof which are useful in reducing the effects of ionizing radiation on animal cells.
2. Discussion of the Background
The events leading up to the end of World War II were punctuated by the dropping of two nuclear bombs on the cities of Hiroshima and Nagasaki. The death, suffering, and permanent damage inflicted on the residents revealed just how devastating the effects of ionizing radiation could be.
These events initiated a vigorous research program into radioprotective agents to minimize the effects of radiation. The most effective agent to emerge from these efforts was S-2-[3-aminopropylamino]ethylphosphorothioic acid (1, WR2721) (U.S. Pat. No. 3,892,824). EQU H.sub.2 N(CH.sub.2).sub.3 NHCH.sub.2 CH.sub.2 SPO.sub.3 H.sub.2 1
Compound 1, is believed to undergo in vitro hydrolysis by the action of phosphatase enzymes to yield compound 2 EQU H.sub.2 N(CH.sub.2).sub.3 NHCH.sub.2 CH.sub.2 SH 2
which is also known to be a radioprotective agent (T. R. Sweeney "A Survey of Compounds From the Antiradiation Drug Development Program of the U.S. Army Research and Development Command", Walter Reed Army Institute of Research, 1979).
Additional research has discovered that 2-(2.varies.-carbamidoethylamino)ethanethiol 3 also shows good radioprotective activity, comparable to that of compound 2 (F. I. Carroll and M. E. Wall, J. Pharm. Sci., 1970, 59, 1350). ##STR1##
The phosphorothioate derivative of compound 3has been prepared (4 WR6458) (U.S. Pat. No. 3,501,557) however the ##STR2## result was a more toxic compound and therefore could not be tested at dose levels comparable to compound 1. At doses lower than the toxic level, no radioprotective activity was observed (see T. R. Sweeney ibid.). It has also been reported that compound 4 is effective for reducing mucin viscosity when administered in dosage rates ranging from 1-100 mg/kg/day (U.S. Pat. No. 4,424,216).
While anti-radiation drug treatment began as an effort to improve the survivability of nuclear war, a more practical aspect of the these research programs is the development of treatments for protecting cancer radiation therapy recipients. Clinical radiotherapy of malignant tumors unavoidably subjects adjacent healthy tissue to damaging radiation. It is desirable to chemically protect normal tissue from radiation injury without adversely affecting the radiosensitivity of the tumor. Even though both malignant and healthy tissue show comparable uptake of the radioprotective agent WR2721, the deficient vascular network of solid tumors reduces the uptake of the radioprotective agent. This partitioning allows for greater effectiveness in radiation treatment. The partitioning effect can be magnified by increasing the uptake of agents in healthy tissue or decreasing the uptake in tumor cells.
There remains a search for radioprotective agents with improved bioavailability and an increased partition coefficient.


A marker detecting section detects markers formed at four corners of a block using binary image data of a two-dimensional code stored in a data memory. A marker's approximate center calculating section calculates the approximate centers of the detected markers. A pattern code detecting means detects a pattern code in accordance with format information of the two-dimensional code stored in a format memory. A marker's real center calculating section calculates the real centers of the markers from the detected pattern code and the format information using the error minimizing method. Based on the calculated real centers of the markers, a data code reading coordinate calculating section calculates reading coordinates for reading data dots of address code and data code areas from the data memory.

1. Field of the Invention
The present invention relates to an information recording medium such as paper on which multimedia information including audio information of voice, music, etc., video information obtained from cameras, video equipment, etc., digital code data obtained from personal computers, wordprocessors, etc. is recorded as a two-dimensional code pattern which can be optically read, a two-dimensional code of the information recording medium, and a system and a method for optically reading the two-dimensional code pattern recorded on the information recording medium and reproducing the original multimedia information.
2. Description of the Related Art
Various recording mediums, such as magnetic tapes and optical disks, have been conventionally known as those for recording voice information, music information, etc. However, even though their reproductions are mass-produced, they increase in unit cost and require a very large space for keeping themselves. Furthermore, it takes time and trouble to transfer a recording medium on which voice information is recorded from one person to another far away therefrom, even though it is mailed or sent by hand. These problems are true of all the so-called multimedia information including video information obtained from cameras, video equipment, etc., digital code data obtained from personal computers, wordprocessors, etc., as well as audio information.
International Publication No. WO 94/08314 (corresponding to U.S. patent application Ser. No. 08/407,018) discloses a system capable of dealing with the above problems. According to this system, multimedia information containing at least one of audio information, video information and digital code data is recorded on an information recording medium, such as paper, in the form of a two-dimensional code formed by two-dimensionally arranging a plurality of dots, i.e., image information or encoded information which can be facsimiled and mass-produced at low cost, and it is reproduced therefrom.
In the system of the international publication, two-dimensional codes are optically read by holding an information reproduction apparatus and manually scanning the recording medium along the two-dimensional codes.
The structure of a two-dimensional code pattern is still being studied so as to improve in recording density. If higher density recording is achieved, the locations of respective dots of the two-dimensional code pattern have to be calculated with high precision. However, such high-precision calculation is not particularly taken into consideration by the above International Publication.
Jpn. Pat. Appln. KOKAI Publication No. 60-165503 discloses a method of reading information with high precision using a considerably large reference image. This method can be applied to a two-dimensional code as disclosed in the International Publication. If it is so, the following problem however will arise.
Assume that a marker is a circle with radius r composed of s dots, the size of a code to be read is a.times.b dots, and the size of one frame is c.times.d dots. If the real coordinates of the code is (i, j), the maximum tolerance for reading the code is (1.+-.a/2, j.+-.b/2). To keep effective precision, therefore, n.sub.x figures obtained by adding the number of figures indicating .+-.a/2 to those (c dots) indicating the X coordinate, are needed along the X-axis, and n.sub.y figures obtained by adding the number of figures representing .+-.b/2 to those (d dots) representing the Y coordinate, are done along the Y-axis. A larger one of n.sub.x and n.sub.y is therefore required on the whole.
For example, if the size of a code to be read is 3.4.times.3.4 dots and that of one frame is 500.times.500 dots, n.sub.x and N.sub.y are each five figures since three figures are required for defining the coordinates and two decimal places are required for representing an error. If the coordinates of s dots constituting the marker are (x.sub.i, y.sub.i) (i=1 to s), its centroid (g.sub.x, g.sub.y) is expressed as follows: ##EQU1## Therefore, the s dots have to be larger than a number in n.sub.x or n.sub.y figures. When the marker includes five figures dots (=ten thousand dots or more), the centroid of the marker can be detected. Since, in this case, .pi.r.sup.2 >10000, the radius r of the marker is 57 dots or more. This marker, which is illustrated in FIG. 1, is very large and thus the recording density is remarkably decreased.

Information recording medium, two-dimensional code, information reproduction system and information reproduction method


A method and circuit for facilitating control of the AC coupling for addressing input offset in an amplifier circuit are provided. In accordance with an exemplary embodiment, a control circuit comprises a pair of resistive networks coupled together through a capacitive coupling, with the pair of resistive networks configured between two amplifier devices of the amplifier circuit. The capacitive coupling is configured to prevent offset in the differences between input voltages to the two amplifier devices, and can comprise various types and configurations of capacitor networks, devices and components. The pair of resistive networks is configured to generate an output current signal from the two amplifier devices while facilitating a substantially identical capacitive loading on the two amplifier devices.

Amplifiers are commonly used to provide gain to an input signal. For example, if a voltage amplifier has a voltage gain of 10, then an input signal of 50 millivolts ("mV") applied to the voltage amplifier results in an output signal of 500 mV. An amplifier typically has a range in which the amplifier operates in a linear manner. For example, a voltage amplifier connected to a 5-volt power supply may be linear for outputs up to 4.5 volts. However, driving output voltages greater than 4.5 volts may force the amplifier into non-linearity, resulting in overload of the amplifier and thus potential inaccuracy. In addition to linearity and noise concerns that can affect accuracy, many amplifier circuits can also be susceptible to input offset. For example, even an input offset of a few millivolts can greatly affect the accuracy of the amplifier circuit.
Many amplifier circuits, such as instrumentation amplifiers, generate a current signal between two amplifier devices through a direct connected resistor. For a direct connection between the amplifier devices, i.e., for DC coupling, such amplifier circuits can generally operate without difficulty. However, if the gain in the amplifier circuit is high, then large offset can occur to decrease accuracy of the amplifier circuit. To address large voltage offset, AC coupling is often implemented, such as through connecting a capacitor between the amplifier devices. In most instances, the capacitor is provided external to the integrated circuit chip containing the amplifier circuits. As a result of an additional bond pad that is utilized and the accumulated stray capacitance, mainly due to the need to configure the bond pad to allow for the connection of the external capacitor, the capacitive loading of the external wiring connections becomes unequal. When the capacitive loading becomes unequal, the ability to achieve low, even harmonic distortion becomes extremely difficult to obtain.

Method and circuit for facilitating control of AC coupling in an amplifier circuit


A power distribution system includes an uninterruptible power supply (UPS) and a power distribution unit including a plurality of interconnected and/or interconnectable guarded connectors coupled to an output of the UPS. Each of the guarded connectors is configured to mate with a guarded connector of a power distribution cable. The power distribution unit may further include a load terminal connected or connectable to the guarded connectors.

The present invention relates to power distribution apparatus and methods and, more particularly, to modular power distribution apparatus and methods.
In some power distribution systems, uninterruptible power supplies (UPSs) and other power sources may be coupled to multiple loads and to one another in various configurations. Custom installation is typically used to construct such systems, e.g., wiring between UPSs, switches, circuit breakers, power distribution units and other devices is installed by a professional electrician using conventional techniques. Such installation typically requires de-energizing while an electrician runs wiring between the components. Maintenance and repair in such systems typically requires similar techniques.

Modular power distribution apparatus using cables with guarded connectors


A system, apparatus, and method for providing an automated translation engine for translating a prescription into a standardized format is generally disclosed. More particularly, embodiments described in this disclosure relate to a system, apparatus, and method for automatically receiving a prescription form, analyzing information provided on the prescription form, and translating the information into a standardized form that details medication information including medication administration directions that are easy for a reader to understand.

Patients may be prescribed medication by a medical doctor to address certain ailments the patient may be suffering. In order to then obtain the medication prescribed by the medical doctor, the patient must generally have the prescription filled through a pharmacy, either at a medical facility or retail location. Therefore, the process generally followed by a patient to fill a prescription includes the patient receiving a prescription from a medical doctor, the patient presenting the prescription to a pharmacy, and the pharmacy filling the prescription by identifying the medication described in the prescription and dispensing the medication to the patient. In addition, the pharmacy may provide directions to the patient for taking the medication contents described in the prescription.
This prescription filling process is labor intensive as it requires the pharmacy to read information from the prescription and manually input medication information and medication directions that will be printed on a label for the patient to read on the dispensed medication. Each pharmacy or pharmacist may input the prescription information differently, and so the labels being provided to patients lacked uniformity.

Automated pharmacy translation engine for prescription medication instructions