Novel arylisothiocyanate compounds are described that are useful for activating alcohol-containing macromomolecules, for example polyethyleneglycols and cellulose, for covalent linkage to amino-groups of biomolecules, for example polypeptides such as antibodies, enzymes, and proteins.

The present invention relates to a novel compound and method for preparation of polyethylene glycol (PEG) adducts of biomolecules, and particularly to PEG adducts of proteins and peptides.
Attachment of large macromolecules such as polyethylene glycol (PEG) to biomolecules such as proteins or peptides via chemical attachment is desired for modification of the properties of the proteins or peptides. Linking to PEG is referred to in the art as xe2x80x9cpegylationxe2x80x9d. Biomolecules circulating in the blood outside of a cell are subject to clearance, and can move through blood vessel walls (extravascularization). Attachment of relatively small biomolecules to large macromolecules can reduce extravascularization, and can enhance the in-vivo circulation half-life of the biomolecule.
Increasing half-life of the biomolecule in circulation is particularly important when the biomolecule is intended for therapeutic use. Pegylation of certain biomolecules reduces kidney clearance and spurious enzymatic degradation and immune system recognition. In xe2x80x9cArtificial Bloodxe2x80x9d, Science, 295:1002, 1004-1005 (Feb. 8, 2002), Jerry E. Squires cites literature reports that conjugation of hemoglobin to macromolecules such as dextran, polyethylene glycol or polyoxyethylene retards the rate at which cell-free hemoglobin is cleared from blood circulation, extending intravascular dwell time up to 48 hours. The alteration of the effective solution volume of the hemoglobin through linkage to a macromolecule alters the colligative properties of cell-free hemoglobin, including osmotic pressure that appears to have a significant effect on blood pressure.
Polyethylene glycol is approved by the U.S. Food and Drug Administration for internal and topical use due to its low toxicity. Additional utilities and features of PEG-biomolecule conjugates are described in Polyethylene Glycol Chemistry: Biotechnical and Biomedical Applications, J. M. Harris, ed. Plenum, NY, 1992 and Polyethylene Glycol Chemistry and Biological Applications, J. M. Harris and S. Zalipsky, eds., ACS, Washington, 1997.
A requisite for preparation of polyethylene glycol conjugates of biomolecules is a suitably activated PEG molecule that under proper conditions reacts with a target biomolecule in an efficient, predictable manner such that the native activity of the target biomolecule is not adversely affected to a significant degree. For sensitive target biomolecules such as proteins and peptides, reactions to form PEG conjugates are best conducted in aqueous, buffered systems in order to avoid denaturation and concomitant loss of biological activity.
Most, if not all, activated polyethylene glycol compounds described in the patent and scientific literature and intended for conjugation to biomolecules such as proteins react with water in addition to the target biomolecule. See, for example, Scheme I below. Typically, the conundrum of derivatizing a target biomolecule in an aqueous medium with a water-sensitive; activated, polyethylene glycol reagent is partially solved by employing a large excess (5-10 fold) of reagent, while maintaining rigorous control of pH and temperature. An objective of any pegylation procedure is to produce pegylated biomolecules with stable, enhanced physiological properties in a predictable and reproducible manner on a meaningful, economical scale.
Scheme 1, below represents a reaction between an activated pegylation reagent of the art and a biomolecule reactant having acidic hydrogens (hydrido groups). The scheme shows the formation of hydrolysis product, pegylated biomolecule and protonated leaving group (HA). As illustrated in Scheme 1, activated pegylation reagents described in the current art often involve production of a leaving group (HA in Scheme 1 below) in addition to any hydrolyzed PEG reagent (shown as PEG-OH). The production of a leaving group presents an additional workup and purification problem during the isolation of the PEG-modified target molecule. The extent of the isolation/purification problem is influenced by the magnitude of the excess reagent employed in order to achieve the desired level of PEG modification which, in turn, is a function of hydrolysis rate of the reagent in water and the coupling rate onto a residue of the target molecule (typically xe2x80x94NH2 or xe2x80x94SH).
Typically, activated polyethylene glycol reagents described and used in the current art are acylating reagents directed toward primary amine residues (xe2x80x94NH2) in the target biomolecule. A common type of PEG acylating reagent is the so-called xe2x80x9cactive esterxe2x80x9d derivative of PEG. Active ester PEGs of the N-hydroxysuccinimide (NHS), hydroxybenztriazole (HBT), imidazole (IM)and p-nitrophenol (PNP) have been described and are commercially available. (See Shearwater Corporation, Catalog 2001, Huntsville, Ala. 35801, www.shearwatercorp.com).
Reagents of the type
mPEG-Rxe2x80x94C(O)xe2x80x94OX,
where R=(O)Cxe2x80x94(CH2)y or (CH2)y or (xe2x80x94Oxe2x80x94),
y=zero through 4, and
X=NHS, HBT, IM or PNP
exhibit half-lives of hydrolysis of 1 minute (or less) to approximately 24 minutes at pH=8 and 25xc2x0 C. Further, as half-life goes up, reactivity goes down. Recommended excesses of PEG acylating reagent vary from equal mass to 10-fold mass relative to target molecule (Shearwater Catalog 2001 p.12). Depending on the molecular weight of the target biomolecule, this recommended mass excess can be greater than a 100-1000 molar excess.
Incorporation of macromolecules such as PEG into biomolecules by using currently-available PEG acylating reagents is a demonstrably inefficient process. Problems associated with the acylating PEG reagents of the current art are exacerbated on a large scale. Variables affecting efficiency and reproducibility of pegylation procedures based on current art acylating reagents include: half-life (t1/2) of hydrolysis, pH value, temperature, time, mixing rate, nature and toxicity of leaving group, ease of product purification from leaving groups and hydrolyzed reagent, as well as the rate and extent of reactivity of the reagent toward the target biomolecule.
The rapid hydrolysis rates of acylating PEG reagents employed by the standard art preclude practical application of multi-functional, crosslinking pegylation reagents of the following type, where A is a leaving group.
A multifunctional, activated PEG reagent as shown above is useful for establishing intramolecular cross-links within protein molecules for the purpose of mapping sub-unit geographies and for stabilization of protein configurations and activities. Rapid hydrolysis rates of standard art PEG reagents, used at large molar excess favor a preponderance of xe2x80x9cone on hitsxe2x80x9d, where one carboxyl end of the bifunctional molecule links to the target protein but the other end hydrolyzes to a carboxylic acid instead of also linking to the protein, and forming stabilizing cross-links.
In a significant advance, workers at the Albert Einstein College of Medicine of Yeshiva University N.Y., University of Iowa and BioAffinity Systems describe a novel approach for activating PEG for attachment to biomolecules that largely circumvents problems associated with hydrolytically unstable reagents. As disclosed in Acharya et al. U.S. Pat. No. 5,585,484, U.S. Pat. No. 5,750,725, U.S. Pat. No. 6,017,943, entitled xe2x80x9cHemoglobin Crosslinkersxe2x80x9d, and Belur N. Manjula, et al., J. Biol. Chem., 275(8):5527-5534 (2000), a maleimide-activated PEG reagent is employed to form stable thioether bonds with an indigenous or added sulfhydryl moiety in the biomolecule. The maleimide function reacts rapidly with xe2x80x94SH groups without significant hydrolysis at pH 6.5-7.0 and without the production of a leaving group as is shown in the reaction below, wherein Rxe2x80x94SH is a sulfhydryl-containing biomolecule.
Biomolecules such as a protein having a paucity of xe2x80x94SH groups must first be reacted with a thiolating reagent such as 2-iminothiolane (or the like) to convert native xe2x80x94NH2 groups from lysine into xe2x80x94SH groups. A practical drawback with the maleimide reagents is that they are difficult molecules to obtain synthetically.
The chemical formula of phenyl isothiocyanate, also known as isothiocyanatobenzene or isothiocyanic acid phenyl ester is shown below.
As noted in the Merck Index, 11th Ed., Susan Budavari, et al., eds., Merck and Co., Inc. (Rahway, N.J.: 1989), p. 7275, phenyl isothiocyanate is known to be used as a derivatizing agent for primary and secondary amines. Such derivatization of primary and secondary amines has typically been used for carrying out Edman degradation and amino acid analyses by HPLC.
This art does not teach the introduction of macromolecules such as polyethylene glycol by the use of a phenylisothiocyanate-containing molecule. Nor are there available any commercial sources of polyethylene glycols or other such macromolecules activated with phenylisothiocyanate. Furthermore, the precursors for obtaining such activated macromolecules are not commercially available or known in the art, e.g. agents containing both a isothiocyanate group and an isocyanate group.
The direct linkage of an alcohol-containing polysaccharide to an amine-containing protein vie reductive amination is known for linking antigenic polysaccharides to carrier proteins for the preparation of vaccines. Aldehyde groups are prepared on either the reducing end [Poren et al. (1985) Mol. Immunol., 22:907-919] or the terminal end [Anderson et al. (1986) J. Immunol., 137:1181-1186] of an alcohol-containing oligosaccharide or relatively small polysaccharide, which are then linked to an amine group in the protein via reductive amination. U.S. Pat. No. 4,356,170 discloses such preparation of useful polysaccharides that are reduced and then oxidized to form compounds having terminal aldehyde groups that can be reductively aminated onto free amine groups of carrier proteins such as tetanus toxoid and diphtheria toxoid with or without significant cross-linking. Several of the problems associated with the attachment of biomolecules to macromolecules are overcome by use of the reagents and processes described hereinafter.
The present invention provides reagents and processes for the linking of alcohol-containing macromolecules, M, to amine-containing biomolecules, B. The compositions of the present invention are linking reagents, linking reagent precursors and reacted linking reagents having (i) an isothiocyanate or a thiourea derivative of an amine-containing biomolecule B, and (ii) one or two other phenyl substituents in the meta- or para-position that is (a) isocyanate, (b) acylazide, or (c) a urethane derivative of an alcohol-containing macromolecule M. Examples of alcohol-containing macromolecules, M, include but are not limited to polysaccharides and hydroxylated silica derivatives. Examples of amine-containing biomolecules, B, include but are not limited to nucleic acids and polypeptides.
A general chemical formula for a linking reagent or linking reagent precursor is shown below having (i) isothiocyanate, and (ii) one or two other phenyl substituents in the meta- or para-position that is (a) isocyanate, (b) acylazide, or (c) a urethane derivative of an alcohol-containing macromolecule M.
The subscript, n, is 1 or 2, denotes the number of R substituents on the phenyl ring. R is xe2x80x94NHC(O)xe2x80x94Oxe2x80x94M, xe2x80x94NCO or xe2x80x94C(O)N3., with R of xe2x80x94NCO or xe2x80x94C(O)N3 in linking reagent precursors. M is a reacted alcohol-containing macromolecule. The R phenyl substituents are in the meta-, di-meta- or para-positions relative to the isothiocyanate group. The di-meta di-substituted phenylisothiocyanate is preferred over the meta, para-di-substituted phenylisothiocyanate.
A general formula for a reacted linking reagent of the present invention is shown below having (i) a thiourea derivative that is a reaction product of an amine-containing biomolecule, B, and an isothiocyanate, and (ii) one or two other phenyl substituents in the meta- or para-position that is a urethane derivative of an alcohol-containing macromolecule, M. The subscript n is 1 or 2, as before.
The isothiocyanate moiety of the linking reagent of the invention reacts with a primary amino group of a biomolecule B to be linked using the linking reagent, to form a thiourea moiety. In the balanced chemical reaction, there is effectively no leaving group from the reaction of the isothiocyanato group with the amino group. Thus, in some embodiments, purification issues due to reaction side products and the costs associated therewith are eliminated.
Some embodiments of linking reagent precursors are chemically facile and relatively inexpensive to prepare. Some embodiments of the linking reagent precursors are stable enough for preparation and shipment with a reasonable shelf life.
In some embodiments of the invention, linking reagents are useful for increasing the hydrodynamic volume of biomolecules, which may prolong the half-life of a biomolecule circulating in blood in a living body. In some embodiments, linking reagents are useful for linking a biomolecule to a surface.
The various embodiments of the present invention has several benefits and advantages, however all embodiments do not necessarily provide all of the below-listed benefits and advantages. Further benefits and advantages of embodiments of the invention will be recognized by workers in the art.
One benefit of several embodiments of the invention is that it provides an embodiment of a novel, activated pegylation reagent that permits rapid, efficient, one-step production of pegylated biomolecules having stable, enhanced physiological properties in a predictable and reproducible manner on a meaningful, economical scale.
An advantage of several embodiments of the invention is that it provides an embodiment of a reagent that does not suffer from a significant hydrolysis rate in aqueous reaction media that are buffered at a pH value of about 5.5 to about 8.5, maintains good rates of reactivity, is specific for primary amine groups in target biomolecules and does not produce a leaving group upon covalent attachment to the target biomolecule.
A further benefit of several embodiments of the invention is that it provides an embodiment that permits direct PEG modification of one or more-amino (preferably xe2x80x94NH2) groups or moieties on the biomolecule without first converting those amino groups to one or more sulfhydryl (xe2x80x94SH) groups.
The present invention provides reagents and processes for the linking of alcohol-containing macromolecules, M, to amine-containing biomolecules, B. The compositions of the present invention are linking reagents, linking reagent precursors and reacted linking reagents having (i) an isothiocyanate or a thiourea derivative of an amine-containing biomolecule B, and (ii) one or two other phenyl substituents in the meta- or para-position that is (a) isocyanate, (b) acylazide, or (c) a urethane derivative of an alcohol-containing macromolecule M. Examples of alcohol-containing macromolecules, M, include but are not limited to polysaccharides and hydroxylated silica derivatives. Examples of amine-containing biomolecules, B, include but are not limited to nucleic acids and polypeptides.
A general chemical formula for a linking reagent or linking reagent precursor is shown below having (i) isothiocyanate, and (ii) one or two other phenyl substituents in the meta- or para-position that is (a) isocyanate, (b) acylazide, or (c) a urethane derivative of an alcohol-containing macromolecule M.
The subscript, n, is 1 or 2, denoting the number of R substituents on the phenyl ring. R is xe2x80x94NHC(O)xe2x80x94Oxe2x80x94M, xe2x80x94NCO or xe2x80x94C(O)N3. M is a reacted alcohol-containing macromolecule. The R phenyl substituents are in the meta-, di-meta- or para-positions relative to the isothiocyanate group.
A general chemical formula for a linking reagent precursor having isothiocyanate and isocyanate moieties is shown below, with n being 1 or 2, as before.
A general chemical formula for a linking reagent precursor having isothiocyanate and the precursor to the isocyanate, an acyl azide, is shown below, with n being 1 or 2, as before.
A general formula for a linking reagent that is a kind of activated alcohol-containing macromolecule is shown below, having an isothiocyanate group and xe2x80x94NHC(O)xe2x80x94Oxe2x80x94M, where M is a reacted alcohol-containing macromolecule, with n being 1 or 2, as before. In a preferred embodiment where n is 1, the isothiocyanate moiety is in the 4-position (para) relative to the xe2x80x94NHC(O)xe2x80x94Oxe2x80x94M.
The isothiocyanate moiety of the linking reagent of the invention reacts with a primary amino group (H2Nxe2x80x94B) to form a thiourea moiety, as shown in Scheme 2 below. In the balanced chemical reaction, there is effectively no leaving group from the reaction of the thiocyanato group with the amino group. The linking reagent can also react with a secondary amine.
Primary amines present in a typical protein are part of a lysine (Lys or K; amino pK=10.5) amino acid residue, and also the amino terminus of the peptide backbone.
A general formula for a reacted linking reagent of the present invention is shown below having (i) a thiourea derivative that is a reaction product of an amine-containing biomolecule, B, and an isothiocyanate, and (ii) one or two other phenyl substituents in the meta- or para-position that is a urethane derivative of an alcohol-containing macromolecule, M. The subscript n is 1 or 2, as before.
Also contemplated is an alcohol-containing macromolecule, M, that is derivatized with more than one phenylisothiocyanate group. A general formula shown below illustrates a macromolecule having two phenylisothiocyanate groups. Such a molecule is useful for cross-linking two biomolecules, B, or two amino groups within a biomolecule.
A preferred form of the reagent for a non-crosslinking pegylation reagent, represented by the formula shown below, is a phenyl isothiocyanate derivative of methoxy-polyethylene glycol (mPEG).
The methoxy-PEG moiety in the formula above is represented by xe2x80x94(O)xe2x80x94CH2CH2xe2x80x94(OCH2CH2)xxe2x80x94Oxe2x80x94CH3, where x is an average repeat unit number that is about 5 and about 500, preferably about 50 to about 300.
A preferred form of the reagent for a crosslinking pegylation reagent, represented by the formula shown below, is a di-(phenylisothiocyanate) derivative of PEG.
The PEG moiety in the formula above is represented by xe2x80x94(O)xe2x80x94CH2CH2xe2x80x94(OCH2CH2)xxe2x80x94Oxe2x80x94, where x is an average repeat unit number that is about 5 and about 500, preferably about 50 to about 300.
A preferred form of the reagent for a linking pegylation reagent where n is 2, represented by the formula shown below, is a di-meta pegylated derivative of phenylisothiocyanate.
The mPEG moiety in the formula above is represented by xe2x80x94(O)xe2x80x94CH2CH2xe2x80x94(OCH2CH2)xxe2x80x94Oxe2x80x94CH3, where x is an average repeat unit number that is about 5 and about 500, preferably about 50 to about 300.
The isothiocyanate moiety of the linking reagent of the invention reacts with a primary amino group of a biomolecule B to be linked using the linking reagent, to form a thiourea moiety. In the balanced chemical reaction, there is effectively no leaving group from the reaction of the isothiocyanato group with the amino group. The linking reagent can also react with a secondary amine. Preferably, for a protein, the primary amine is from the side chain of lysine or the amino terminus.
A contemplated biomolecule may be a polypeptide such as an antibody, enzyme, or protein, or a nucleic acid. Some exemplary polypeptides that benefit from pegylation include, but are not limited to, hemoglobin, bilirubin oxidase and insulin. Several contemplated biomolecules are discussed in Polyethylene Glycol Chemistry: Biotechnical and Biomedical Applications, J. M. Harris, ed. Plenum, NY, 1992 and Polyethylene Glycol Chemistry and Biological Applications, J. M. Harris and S. Zalipsky, eds., ACS, Washington, 1997. In another embodiment, the invention contemplates the linkage of the isothiocyanate to an amine of a biomolecule that is not a typical peptide residue. The invention contemplates the linking of an amine-containing biomolecule such as a drug or pro-drug, a hapten, a cytokine, a ligand for a receptor, a peptide analog, a nucleic acid base or nucleic acid analog.
In a method for providing a pegylated protein, an amine-containing protein is linked to a large, alcohol-containing PEG macromolecule, such as a PEG-phenyl isothiocyanate compound. Such a pegylated protein provides a protein that can circulate in the blood with a longer half-life than the non-pegylated protein.
In a method for providing an antibody linked to a surface, an amine-containing antibody is linked to an alcohol-containing cellulose derivatized with a phenyl isothiocyanate compound. Such a linked antibody is useful, for example in methods where separation between material that binds to the antibody from material that does not bind to the antibody is desired.
In a method for providing a protein linked to a surface, an amine-containing antibody is linked to an alcohol-containing cellulose derivatized with a phenyl isothiocyanate compound.
In a method for providing a ligand linked to a surface, an amine-containing ligand is linked to an alcohol-containing surface that has been derivatized with a phenyl isothiocyanate. Such a linked ligand is useful, for example in methods where separation between material that binds to the ligand from material that does not bind to the ligand is desired. Such an alcohol-containing surface might be a cellulose membrane or a silica bead having reactive hydroxyl groups.
In a method for providing a multi-subunit protein with enhanced stability, amine-containing proteins are crosslinked intramolecularly with a bifunctional alcohol-containing molecule, such as a PEG di-(phenylisothiocyanate) compound. Such a cross-linked multisubunit protein is useful, for example in studies of the relationships between subunits or to ascertain what proteins are in a complex, such as a transcription complex with effectors.
In an embodiment where n is 1, the R group is preferably in the para position. Thus, in a preferred embodiment where n is 1, the isothiocyanate moiety is in the 4 position (para) relative to the isocyanate (xe2x80x94NCO), xe2x80x94C(O)N3, or xe2x80x94NHC(O)xe2x80x94Oxe2x80x94M moiety.
In an embodiment where n is 2, there are two R substituents on the phenyl ring. The di-meta di-substituted phenylisothiocyanate is preferred over the meta, para-di-substituted phenylisothiocyanate. In an embodiment where n is 2, the invention contemplates R groups that are not identical, such as different M groups in xe2x80x94NHC(O)xe2x80x94Oxe2x80x94M, or an xe2x80x94NCO group and an xe2x80x94NHC(O)xe2x80x94Oxe2x80x94M group. Thus, reaction of less than 100 percent of the xe2x80x94NCO to form xe2x80x94NHC(O)xe2x80x94Oxe2x80x94M is contemplated, as is the use of a mixture of macromolecular forms (e.g. PEG that has a range of chain lengths, as is typical in some commercially available PEG preparations).
The azido compound, where R is xe2x80x94C(O)N3, is stable, and is contemplated for use as a general precursor linking reagent. When R is xe2x80x94NHC(O)xe2x80x94Oxe2x80x94M, M is an alcohol-containing macromolecule is derivatized with one or more, but preferably only one or two, phenylisothiocyanate groups. Where M is derivatized with more than one phenylisothiocyanate group, the reagent is a crosslinking reagent. Where M is PEG, and M is derivatized with more than one phenylisothiocyanate group, the reagent is a crosslinking pegylation reagent.
The invention contemplates the linkage of the isothiocyanate group to an amine, preferably a primary amino group of a biomolecule B to be linked using the linking reagent. Such a biomolecule is preferably a nucleic acid or a polypeptide, e.g. an antibody, enzyme, or protein.
In an embodiment, the invention contemplates the linkage of the isothiocyanate to an amine of a biomolecule that is not a typical peptide residue. The invention contemplates the linking of an amine-containing biomolecule such as a drug or pro-drug, a cytokine, a ligand for a receptor (e.g. example streptavidin), a peptide analog, a nucleic acid base or nucleic acid analog.
In a method for providing a pegylated polypeptide, an amine-containing polypeptide is linked to a large, alcohol-containing PEG macromolecule, such as a PEG-phenyl isothiocyanate compound. Such a pegylated polypeptide provides a polypeptide that can circulate in the blood with a longer half-life than the non-pegylated form. Such a pegylated polypeptide is thus useful in a method of treating a mammal (including homo sapiens) involving the administration of a polypeptide.
The invention contemplates a method of making a stabilized peptide through attachment of a polyethylene glycol to a peptide. In a preferred embodiment, a bifunctional molecule (a phenyl group with an isothiocyanate moiety and an isocyanate moiety) serves to crosslink the polyethylene glycol moiety to a peptide via an amine group, preferably a primary amino group, such as on a lysine side chain.
A polyethylene glycol (PEG) compound can itself be quite varied in composition, but contains at least one poly(oxyethylene) chain [(xe2x80x94CH2CH2Oxe2x80x94)x] having an average molecular weight of about 300 (x is 5) to about 22,000 (x is 500), with an average molecular weight of about 2,300 (x is 50) to about 13,300 (x is 300) being more preferred. More specifically, the reacted PEG compound group M of the linker corresponds to the formula xe2x80x94CH2CH2xe2x80x94(CH2CH2O)nxe2x80x94CH2CH2Y where X, n and R are defined and discussed hereinbelow.
In the above formula, x is a number having an average value of about 5 to about 500, and more preferably about 50 to about 300. It is well known that the higher molecular weight PEG compounds are usually mixtures rather than pure compounds having a single molecular weight. As a result, x, the number of ethyleneoxy repeating units, is a number that is an average number. The terminal Y group is xe2x80x94OH or a C1-C10 hydrocarbyl ether (alkoxy group) having a molecular weight of up to about one-tenth of the xe2x80x94(CH2CH2O)nxe2x80x94 portion.
Exemplary C1-C10 hydrocarbyl ether groups are well known and include alkyl, alkenyl, alkynyl and aromatic ethers. Illustrative C1-C10 ethers thus include methyl, which is most preferred, ethyl, isopropyl, n-butyl, cyclopentyl, octyl, decyl, 2-cyclohexenyl, 3-propenyl, phenyl, 1-naphthyl, 2-naphthyl, benzyl, phenethyl and the like ethers. These ether groups can also be named methoxy, ethoxy, isopropoxy, n-butoxy, cyclopentyloxy, octyloxy, decyloxy, 2-cyclohexenyloxy, 3-propenyloxy, phenoxy, 1-naphthoxy, 2-naphthoxy, enzyloxy and phenethyloxy. A C1-C6 hydrocarbyl group is a particularly preferred Y group.
The molecular weight of a C1-C10 hydrocarbyl ether can be up to about one-tenth of the weight of the xe2x80x94(CH2CH2O)xxe2x80x94 portion of the PEG group. Thus, where x is 20, the xe2x80x94(CH2CH2O)xxe2x80x94 portion has a molecular weight of 880 (20xc3x9744) so that the molecular weight of Y can be up to about 90, or about the weight of a phenoxy group. It is more preferred that the molecular weight of the C1-C10 hydrocarbyl group be about 0.2 to about 2 percent of the molecular weight of the xe2x80x94(CH2CH2O)xxe2x80x94 portion.
The linker molecules of the invention are useful in a variety of methods and assays involving amine-containing peptides or proteins. The invention can be used so that detection enzymes are the amine-containing biomolecule B that is linked to a macromolecule or surface, M, such as cellulose, for use in an assay. Skilled workers in the art can appreciate other methods of using the linker of the invention in their assays with their own amine-containing biomolecules, B, and alchohol-containing macromolecules, M.
For example, streptavidin, such as the wild type or mutants taught in U.S. Pat. No. 6,312,916 granted Nov. 6, 2001, can be useful in binding biotinylated molecules. The streptavidin is linked to a macromolecule, such as PEG, which can change a molecular weight cut off and permit dialysis-type binding assays. The streptavidin B is linked to a macromolecule such as a cellulose membrane, M, which can then be washed with solutions that may contain biotinylated molecules.
Contemplated hydroxy-containing surfaces include, but are not limited to, appropriately derivatized silica, cellulose or gold.
Contemplated hydroxy-containing macromolecules include polysaccharides. On large polysaccharides, one or more of the hydroxy groups may be reacted with a linking reagent precursor. Reaction with a di-meta compound may result in crosslinking of a polysaccharide chain. The carbohydrate itself can be synthesized by methods known in the art, for example by enzymatic glycoprotein synthesis as described by Witte et. al. (1997) J. Am. Chem. Soc., 119:2114-2118.
Several oligosaccharides, synthetic and semi-synthetic, and natural, are discussed in the following paragraphs as examples of oligosaccharides that are contemplated haptens to be used in making a HBc conjugate of the present invention. U.S. Pat. No. 4,220,717 also discloses a polyribosyl ribitol phosphate (PRP) hapten for Haemophilus influenzae type b. Andersson et al., EP-0 126 043-A1, disclose saccharides that can be used in the treatment, prophylaxis or diagnosis of bacterial infections caused by Streptococci pneumoniae. European Patent No. 0 157 899-B1, the disclosures of which are incorporated herein by reference, discloses the isolation of antigenic pneumococcal polysaccharides.
The optimal ratio of macromolecule polysaccharide M to biomolecule B in the linked form depend on the particular polysaccharide, the biomolecule, and the linker molecule used.
In a method for providing an antibody linked to a surface, an amine-containing antibody is linked to an alcohol-containing cellulose derivatized with a phenyl isothiocyanate compound or other hydroxy-containing surface. Such a linked antibody is useful, for example in methods where separation between material that binds to the antibody from material that does not bind to the antibody is desired.
In a method for providing a protein linked to a surface, an amine-containing antibody is linked to an alcohol-containing cellulose derivatized with a phenyl isothiocyanate compound.
In a method for providing a ligand linked to a surface, an amine-containing ligand is linked to an alcohol-containing cellulose derivatized with a phenyl isothiocyanate. Such a linked ligand is useful, for example in methods where separation between material that binds to the ligand from material that does not bind to the ligand is desired.
In a method for providing a multi-subunit protein with enhanced stability, amine-containing proteins are crosslinked intramolecularly with a bifunctional alcohol-containing molecule, such as a PEG di-(phenylisothiocyanate) compound. Such a cross-linked multisubunit protein is useful, for example in studies of the relationships between subunits or to ascertain what proteins are in a complex, such as a transcription complex with effectors. Also contemplated is linking between different molecules in an associated complex, for example transcription factors with RNA polymerase.
A preferred pegylation reagent according to the invention is made using methods known in the art or their equivalents.
In one example of the invention, the preparation of a PEG molecule having a phenyl isothiocyanate activating group is carried out as shown in Scheme 3, below. Briefly, a para-aminobenzoic acid is reacted with thiophosgene to produce 4-carboxyphenyl isothiocyanate, as described in Example 1. The carboxy moiety is activated as the azide to form isothiocyano benzoyl azide by known methods, such as that described in Example 2. The azide-activated carboxy moiety was then heated to cause internal rearrangement to isocyanophenyl isothiocyanate, by the Curtius Rearrangement described in Example 3.
The invention contemplates lirking reagents having one equivalent of hydroxy-containing macromolecule. A contemplated linking reagent is not limited to a para-substituted phenyl isothiocyanate. Meta- and di-meta-substituted phenyl isothiocyanate compounds are also contemplated. The synthesis of the para-substituted compound is shown below in Examples 1-3, starting with para-aminobenzoic acid. A corresponding meta-substituted aminobenzoic acid compounds are commercially available.
The invention contemplates bifunctional linking reagents having more than one phenyl isothiocyanate groups, which are useful as crosslinking reagents. Using the azide-activated synthetic isocyanate reaction described above, a hydroxy-containing macromolecule is linked to the phenyl isothiocyanate group. The use of a macromolecule with more than one hydroxy group, and appropriate adjustments of stoichiometry and reaction conditions, results in a reagent that has more than one phenyl isothiocyanate group. For example, a bifunctional PEG reagent is made using a PEG diol, as illustrated by Example 4, below. Such bifunctional linking reagents are useful for linking two amine-containing biomolecules (the same or different biomolecules).
The invention contemplates linking reagents having one or more hydroxy-containing macromolecules on a single phenyl isothiocyanate group. Such reagents are made using the analogous procedures to those described herein in detail for the mono-substituted phenyl isothiocyanate compound. For example, a di-meta reagent is made starting with 5-aminoisophthalic acid, commercially available (e.g. Aldrich Product No. 18,627-9). The conversion of the amino group to isothiocyanate then proceeds as described in the Examples below, using CSCl2, NaOAc and H2O, using methods known in the art. A preferred method of making a di-meta reagent is shown in Scheme 4 below. Commercially available amino isophthalic acid serves as the starting material that is converted to the corresponding isothiocyanate compound, 3,5-dicarboxyphenyl isothiocyanate, using thiophosgene, C(S)Cl2, in the presence of an aqueous solution of sodium acetate as illustrated below in Example 5. The two carboxylic acid moieties are then activated with sodium azide in the presence of phenyl dichlorophosphate and pyridine, as illustrated in Example 6 below, to provide the corresponding acylazido phenylisothiocyanate. The acylazido moieties convert smoothly to isocyanate moieties via the Curtius rearrangement, which then react with an alcohol-containing macromolecule, such as PEG, to provide a contemplated di-meta-substituted phenylisothiocyanato reagent.
The linking of two hydroxy-containing macromolecules to the di-meta-substituted reagent also proceeds by methods known in art, examples of which are provided hereinbelow. Preferably, one hydroxy group from each of two macromolecules reacts with a single di-meta isocyanate-substituted phenyl isothiocyanate compound to form a di-meta linking reagent.
Thus is it recognized that the methods described herein are useful to activate a variety of hydroxy-containing macromolecules, including hydroxy and polyhydroxy compounds. Contemplated examples include but not limited to methoxy PEG, PEG-diols and branched PEGs of various molecular weights. Hydroxy and polyhydroxy compounds other that polyethylene glycols are contemplated, including but not limited to celluloses and starches. Such reagents adapting methods known in the art for reacting phenylisocyanates with hydroxl-containing molecules, such as described herein adapted for the molecules of interest, by adjusting the amount of p-isothiocyanobenzoylazide added to match the correct stoichiometry of macromolecular hydroxyls present. Normally, a stoichiometric or slight excess (zero to ten percent molar excess relative to the hydroxy; where zero percent excess is a one-to-one molar ratio) of the azide is added. For instance, dry, insoluble surfaces, i.e., cellulose bearing a plurality of primary hydroxyl groups is activated by soaking the surface in a solution of p-isothiocyanophenyl isocyanate at 20-60xc2x0 C. (prepared in situ), as described in Example 5, below, or hydroxy-derivatized silica. The activated surface is ready for linking to an amine-containing molecule, useful for a wide variety of applications.
The activated supports thus obtained are useful for immobilizing functional proteins such as enzymes or antibodies under mild conditions (e.g. pH 7.4-8.25 10 mm bicarbonate buffer). Likewise, immunoconjugates of small, hydroxy-containing haptens, e.g. vitamin B-12, hydroxyprogesterone, and digoxigenin, are made utilizing a contemplated isothiocyanophenyl isocyanate. A protocol for linking small, hydroxy-containing molecules to an isocyanate compound is described in M. E. Annunziato, et al., Bioconjugate Chem., 4:212-218 (1993), the disclosures of which are incorporated in full herein by reference.
The phenyl isothiocyanate moiety is stable against hydrolysis in aqueous buffers, and it maintains excellent rates of reaction specifically with primary amines in target biomolecules. Bi- and multi-functional linking reagents are thus possible and practical for the efficient derivatization of target molecules for the purpose of establishing inter and/or intra molecular crosslinks which stabilize native tertiary structure.


The invention is a rotary joint for singlemode optical fibers, having a fixed and a rotating part to permit the transmission of optical signals across a rotational interface (such as a winch or turret) with minimal insertion loss and, in particular, low reflections (good return loss). There is no need of conversion to electrical signals; the device is passive. It may be use an oil of refractive index matched to that of the glass fibers and to that of fiber tapers or lenses used to expand the beam emitted from one fiber and contract it for transmission into the other fiber. The device is bidirectional. By use foil, through precision techniques for building and mounting the optical and mechanical components, and by use of advanced bearings, both the insertion loss and unwanted reflections (return loss) can be minimized, thereby making it suitable for use with singlemode fiber. Insertion loss can be further reduced in conjunction with index-matching fluid by using optical elements (lenses, tapers, fibers) having angled or curved facets rather than perpendicular facets. Oil filling has the further advantage of pressure compensation allowing the device to operate at any ambient pressure. Lenses having curved surfaces can be accommodated by the use of fluid having a refractive index different from that of the lens material.

The properties of optical fiber make it an ideal medium for carrying signals in an ever-increasing number of applications. These properties include high bandwidth, i.e. signal carrying capacity, immunity to interference, low loss, light weight and low bulk. Optical fiber is often used in conjunction with electrical leads for carrying power, in applications such as underwater sensor arrays and remotely operated vehicles for pipeline inspection and repair. In such applications the composite cable is winched from the surface vessel. This requires a slip ring or rotary joint assembly at the winch, to permit the payout or retraction of cable while allowing continuous operation of the underwater system.
Electrical slip rings for the copper wires carrying power are well established, but fiber optic rotary joints are much more recent developments and have not been perfected to an adequate state for many applications. In some systems, wherein optical fiber has been used for signal telemetry, it was necessary to convert the optical signals to electrical signals within the winch drum, thereby losing some of the benefits of fiber optics through exposure to interference as well as introducing failure-prone and expensive components.
The use of fiber optic rotary joints has been limited by their performance. The few fiber optic rotary joints that have been reported have losses of typically 3 dB for insertion loss and -20 to -25 dB for return loss. These figures, which are for multimode fiber, are inadequate for some applications; more importantly, they are unacceptable for use with laser based singlemode fiber systems. Singlemode fiber of the type used in long-haul telecommunications is increasingly chosen for short-haul applications such as those given above, to capitalize on its higher bandwidth, lower loss and other advantages.
Oil-filling has been mentioned in other disclosures (U.S. Pat. No. 4,725,116) but not in the context of reducing return loss to permit singlemode operation.
The invention described herein gives several improvements in the state of the art of fiber optic rotary joint technology, accommodating many applications which were previously not satisfactorily addressed.


A vehicle detector includes a detecting apparatus and a determining apparatus. If a plurality of detection points detected by the detecting apparatus forms a group of detection points, the determining apparatus sets a determining virtual window encompassing the group of detection points and determines whether the group of detection points is likely to represent the one vehicle based on a state of movement of the group of detection points with respect to the determining virtual window.

1. Field of the Invention
The present invention relates to vehicle detectors and vehicle detecting methods and in particular to a vehicle detector and a vehicle detecting method suitable for detecting another vehicle existing in the vicinity of a vehicle.
2. Description of the Related Art
A known vehicle-mounted driving aid apparatus determines the distance between a first vehicle on which the driving aid apparatus itself is mounted (hereinafter also referred to as a host vehicle) and a second vehicle ahead of or behind the first vehicle by detecting the second vehicle using a radar apparatus, so that, if the distance is too short, the driver of the first vehicle is warned or the speed of the first vehicle is restricted to avoid a collision (refer to, for example, Japanese Unexamined Patent Application Publication No. 2003-99762).
The radar apparatus used in such a driving aid apparatus receives reflected electromagnetic waves, such as microwaves or laser beams, emitted toward the second vehicle and detects the second vehicle based on the result of the received reflected waves.
More specifically, if radar reflection points in a radar pattern indicate a low speed relative to the host vehicle and form one group of many reflection points with intensities above a predetermined level, the group of reflection points is regarded as a vehicle, thus discriminating the vehicle from road noise.
However, since reflection points detected by the radar apparatus differ depending on, for example, the radar radiating position in the vehicle, the number of reflection points constituting the detected group is unreliably in some cases.
Furthermore, if a plurality of groups of reflection points exists such that the groups are close to one another, i.e., if the groups of reflection points are too close to one another, two vehicles are mistakenly regarded as one large vehicle.
Thus, the known vehicle-mounted driving aid apparatus has a problem that it is difficult to detect the second vehicle accurately and reliably.

Vehicle detector and vehicle detecting method


An oven includes an interior cavity and a convection heating system for developing a flow of heated air within the interior cavity. The convection heating system includes a plurality of fans to provide a plurality of airflows, and a single convection heating element for heating the plurality of airflows. A shroud is arranged in covering relationship over the convection heating system and includes at least one intake aperture, and a plurality of exhaust apertures for discharging air from the plurality of fans back into the interior cavity. A baffle is located within the shroud and generally between adjacent ones of the plurality of fans. The baffle inhibits mixture of the airflows of each of the fans within the shroud. In one example, a first fan provides a first airflow, a second fan providing a second airflow, and the baffle inhibits mixture of the first and second airflows within shroud.

Appliances, such as ovens, often have one or more racks generally within the appliance for the placing of cookware, food, and other items within the oven. Additionally, one or more heating elements are provided for heating and cooking the food or other items located within the oven.
In a conventional oven, the oven cavity temperature is controlled by a temperature regulator that turns the heating element on or off as necessary. In addition or alternatively, some ovens further include a convection heating system that typically includes either a gas-fired combustion chamber separate from the oven cavity, or a resistive heating element energized by an electric current, but may also include other types of heating elements such as, for example, an infrared energy source.
A convection oven heats an object in an oven cavity by transferring heat energy from heating elements to the object by circulation of a gas within the oven cavity. Typically, a thermal sensor senses the temperature of the gas and a regulator controls the operation of the heating elements in response to the sensed temperature to maintain a desired operating temperature in the oven cavity. Although the circulated gas in a convection oven for cooking food is typically air, other gases may be employed such as nitrogen, steam, or combustion gases from gas-fired burners, depending upon the oven application. Thus, although convection ovens are commonly used for cooking and baking food, convection oven applications are not limited to cooking and baking. Convection ovens may also be employed in industrial or commercial applications that do not directly cook food.
It is generally known that using a blower, such as a fan, to promote air circulation can dramatically improve the uniformity of air temperature distribution within the oven cavity of a convection oven. However, unmanaged air flow can still be uneven, leading to undesirable cooking or drying of foods.


An apparatus for continuously laying a pipeline on the floor of a body of water from a pipelaying vessel includes: a generally cylindrical reel with an axis upon which the pipeline is wound, a stinger provided at the stern of the vessel for guiding the lowered pipeline, a launch device configured to control lowering of the pipeline over the stinger of the vessel and into the body of water. This apparatus further includes a frame supporting the reel and the launch device, adapted to be moveable with respect to the vessel in the longitudinal direction of the pipeline, and a tension device to be mounted between the frame and the vessel, adapted to control the pipeline tension in a predetermined tension range during pipelaying.

1. Field of the Invention
The present invention relates to an apparatus for continuously laying a pipeline on the floor of a body of water from a pipelaying vessel. The apparatus comprises a reel upon which a pipeline to be laid is wound. The apparatus also includes a stinger or other curved path pipeline guiding arrangement (e.g. a curved track, a wheel or chute) provided at the stern of the vessel for guiding the lowered pipeline. The apparatus further includes launch means for the controlled lowering of the pipeline over the stinger of said vessel and into the body of water.
2. Description of Background Art
Such a vessel is well known, e.g. from U.S. Pat. No. 3,965,713. A reel with a substantially vertical axis is provided, and the launch means in this embodiment are formed by tensioning means. During pipelaying, it is important to control the pipeline tension in a predetermined tension range. There is a risk of overstressing (too much tension in a pipe) or buckling (too low tension) in the pipeline section that has left the reel and has not yet reached the floor of the body of water. In particular the pipeline sections in the vicinity of the floor of the body of water and in the vicinity of the surface of the body of water can be subjected to stresses deviating from what is acceptable.
To keep the vessel at a desired position with respect to the lowered pipeline, often anchors are used. Multiple anchors and anchor handler vessel(s) are then required to perform the pipelaying operation and to control the position of the vessel accurately. A large offset is not desired for pipelaying operations, because it will result in pipeline tension outside the predetermined allowable tension range. Hence, accurate anchoring is required to control the pipeline tension.
A disadvantage of such a positioning system is that anchor handling is time-consuming and complex.
Therefor, alternatively the pipelaying vessel is kept in place by a dynamic positioning system controlling a suitable propulsion system of the vessel, e.g. with multiple thrusters, such as described in U.S. Pat. No. 6,328,502. However, a disadvantage of such systems is the limited accuracy. The actual position of the vessel may vary up to several meters offset from the desired position, which is found to be problematic in pipelaying, in particular when pipelaying is relatively shallow water, e.g. the North Sea.


One embodiment of the present invention provides a system that dynamically adjusts the aggressiveness of an execute-ahead processor. If a data-dependent stall condition is encountered during program execution, the system enters an execute-ahead mode, wherein instructions that cannot be executed because of the unresolved data dependency are deferred, and other non-deferred instructions are executed in program order. If a non-data-dependent stall condition is encountered during execute-ahead mode, the system enters a scout mode, wherein instructions are speculatively executed to prefetch future loads, but results are not committed to the architectural state of the execute-ahead processor. On the other hand, if an unresolved data dependency is resolved during the execute-ahead mode, enters a deferred mode and executes deferred instructions. During this deferred mode, if some instructions are deferred again, the system determines whether to resume execution in the execute-ahead mode. If it determines to do so, the system resumes execution in the execute-ahead mode, and otherwise resumes execution in a non-aggressive mode.

1. Field of the Invention
The present invention relates to techniques for improving the performance of computer systems. More specifically, the present invention relates to a method and an apparatus for speeding up program execution by dynamically adjusting the aggressiveness of an execute-ahead processor, wherein the execute-ahead processor selectively defers execution of instructions with unresolved data-dependencies as they are issued for execution in program order.
2. Related Art
Advances in semiconductor fabrication technology have given rise to dramatic increases in microprocessor clock speeds. This increase in microprocessor clock speeds has not been matched by a corresponding increase in memory access speeds. Hence, the disparity between microprocessor clock speeds and memory access speeds continues to grow, and is beginning to create significant performance problems. Execution profiles for fast microprocessor systems show that a large fraction of execution time is spent not within the microprocessor core, but within memory structures outside of the microprocessor core. This means that the microprocessor systems spend a large fraction of time waiting for memory references to complete instead of performing computational operations.
Efficient caching schemes can help reduce the number of memory accesses that are performed. However, when a memory reference, such as a load operation generates a cache miss, the subsequent access to level-two (L2) cache or memory can require dozens or hundreds of clock cycles to complete, during which time the processor is typically idle, performing no useful work.
A number of techniques are presently used (or have been proposed) to hide this cache-miss latency. Some processors support out-of-order execution, in which instructions are kept in an issue queue, and are issued "out-of-order" when operands become available. Unfortunately, existing out-of-order designs have a hardware complexity that grows quadratically with the size of the issue queue. Practically speaking, this constraint limits the number of entries in the issue queue to one or two hundred, which is not sufficient to hide memory latencies as processors continue to get faster. Moreover, constraints on the number of physical registers that are available for register renaming purposes during out-of-order execution also limits the effective size of the issue queue.
Some designers have proposed a scout-ahead execution mode, wherein instructions are speculatively executed to prefetch future loads, but wherein results are not committed to the architectural state of the processor. For example, see U.S. Pat. No. 6,415,356, entitled "Method and Apparatus for Using an Assist Processor to Pre-Fetch Data Values for a Primary Processor," by inventors Shailender Chaudhry and Marc Tremblay. This solution to the latency problem eliminates the complexity of the issue queue and the rename unit, and also achieves memory-level parallelism. However, it suffers from the disadvantage of having to re-compute any computational operations that are performed while in scout-ahead mode.
Hence, what is needed is a method and an apparatus for hiding memory latency without the above-described drawbacks of existing processor designs.

This patent is subject to a terminal disclaimer.

Method and apparatus for dynamically adjusting the aggressiveness of an execute-ahead processor to hide memory latency


A bipolar transistor and method of fabricating the same is disclosed. Particularly, a bipolar transistor may have an emitter and a collector diffusion layer in the sidewalls and the bottom of a device isolation trench. A method includes the steps of: forming a device isolation trench in a substrate; forming a photoresist pattern and implanting ions into the sidewalls and the bottom of the trench to form an emitter and a collector; removing the photoresist pattern; and filling the trench with an insulation layer to form the device isolation structure. Accordingly, the transistor and method can minimize device area by forming the diffusion layer of an emitter and a collector in the sidewalls and the bottom of the trench, and can provide a deep impurity diffusion layer without a high temperature diffusion process. In addition, the transistor and method can provide both a high amplification factor and a high current driving force.

1. Field of the Invention
The present invention relates to a bipolar transistor and a method of fabricating the same, and more particularly, to a bipolar transistor having an emitter and a collector diffusion layer in the sidewalls and the bottom of a device isolation trench and a method of fabricating the same.
2. Background of the Related Art
Due to a great interest in a composite semiconductor, whose memory and logic are formed within a single chip, its usage is increasing. Because the composite semiconductor device can integrate memory and logic into a single chip and manufacture the same in a single process, it can operate faster and use less electric power than existing combinations of chips without any substantial change of design.
On the other hand, as the manufacturing processes of memory products and logic products are simultaneously performed, the size of the single chip is getting larger and, therefore, there are a lot of difficulties in conducting the manufacturing process. In addition, the transistor in the memory focuses on prevention of leakage current rather than providing a high current driving force. On the other hand, logic product transistors sometimes require a high current driving force. Such mixed function products (i.e., containing both memory and logic) need to be manufactured with both characteristics.
An example of a conventional method of fabricating bipolar transistors in semiconductor devices is illustrated in the accompanying drawings, in which FIG. 1 is a top view of a bipolar transistor in a conventional composite semiconductor, and FIG. 2 is a cross -sectional view of the conventional bipolar transistor along the line A-A′ in FIG. 1.
As illustrated in FIG. 1 and FIG. 2, after the formation of a device isolation region in a semiconductor substrate, an N-type well 10 is formed in a predetermined region of the semiconductor substrate and a P-type well 11 having a predetermined depth is formed in the N-type well 10. Here, the thickness of the P-type well 11 is generally between 1 and 1.2 μm. Therefore, it is difficult to realize the transistor that has a high amplification gain. On the other hand, a DRAM bit line that will be formed in a later process can not be formed in the P-type junction because it uses N-type doped silicon. Therefore, the first N+ region 14 is formed in the P-type well 11. After the source/drain junction of a DRAM transistor is formed, or P+ region 13 is formed in the P-type well 11, the second N+ region 12 is formed for collector pick-up in the N-type well 10.
Metal contacts are formed respectively for the first and second N+ regions 14 and 12 and the P+ region 13 in the later processes (not shown), which function as an emitter, a base and a collector, respectively. That is, the first N+ region 14 becomes the emitter, the P+ region 13 becomes the base, and the second N+ region 12 becomes the collector.
Although the existing method of fabricating the bipolar transistor as described above integrates both the memory and the logic as a semiconductor device into a single chip and in a single process, it is difficult to make a transistor that has a high amplification gain because of the depth of well, and to form both the emitter and the collector that have deep junction depth because of limitations on the source/drain diffusion layer that are formed in the memory transistors at the same time. Therefore, a direct current amplification factor (hfe) and/or the implantation efficiency of holes is low.

Methods of fabricating bipolar transistor with emitter and collector in separate device isolation trenches


A power amplifier apparatus may include an amplifier configured to amplify an input signal and a delay transferring circuit connected between an input terminal and an output terminal of the amplifier, the delay transferring circuit configured to delay the input signal to transfer the delayed input signal to the output terminal of the amplifier.

1. Field
The present disclosure relates to a power amplifier and a phase correction method for a power amplifier.
2. Description of Related Art
Recently, there has been rapid progress in wireless transmission and reception systems, and a system having high linearity characteristics has been gradually required in accordance with the demand for a more accurate and high data transmission rate. In accordance with the above-mentioned demand, linearity characteristics of a power amplifier (PA), an amplifier of a final amplifying stage processing a large signal in the wireless transmission and reception system, has become increasingly important.
In addition, the power amplifier is generally a necessary part of a transmitter, and accounts for a disproportionately large part of the power consumption of the overall system as well as a role of the transmitter. That is, in order to improve efficiency characteristics of the overall system, there is a need to improve efficiency characteristics of the power amplifier.
Therefore, in order for the power amplifier to transmit a signal which is substantially undistorted in a wireless transmission and reception stage with a low degree of energy, a solution to improve linearity characteristics and power efficiency characteristics of the power amplifier may be beneficial.

Power amplifier and phase correction method therefor


In one aspect of the invention, methods of synthesizing iron phosphate precursors and lithium iron phosphate active material usable for a lithium secondary battery include the steps of first forming fine particle iron phosphate precursors hydrated and anhydrous, then forming electrode active material lithium iron phosphate with said iron phosphate precursors. The unique methods are generally efficient and cost effective, as well as stable and scalable for a high performance electrode active material with high capacity, good discharge profile, high electronic conductivity, as well as long cycle life.

Since the ordered olivine lithium iron phosphate (LiFePO4) was discovered by Goodenough et al [1], it has been extensively and intensively studied as a cathode material for lithium ion battery due to its advantages include a high theoretical specific capacity (170 mAh/g), long cycle ability, high safety , low toxicity and potential for low cost [1,2], and much efforts have been made to understand and improve the performance of LiFePO4 in the past decade. Recently, Olivine LiFePO4 has been considered as the most promising cathode candidate for the next generation large-scale lithium ion battery used for hybrid electric vehicles (HEVs), electric vehicles (EVs) and large-scale energy storage systems for the sustainable energy needed for a low carbon society, such as the wind and solar power [3].
It is well-known in the lithium ion battery community that the slow diffusion of lithium ion and/or the low electronic conductivity in LiFePO4 limits its application as the power supply [2,5]. This apparent drawback had been compensated greatly in recent years through various materials synthesis and/or processing approaches, including the use of carbon coatings [6,7], particle size minimization [2, 8-13] and multivalent metal ions doping [14-16] and so on.
Recently, synthesized methods of LiFePO4 which take full considerations of carbon coating, particle size minimization and/or metal ions doping are gained more and more attention for improving the performances of cathode materials in terms of energy density, power density (rate capability), cycle life (stability). Nanosize carbon coated LiFePO4 cathode materials display very excellent electrochemistry properties. Kang and Ceder [17] obtained LiFePO4/C material with the size of about 50 nm by solid-state reaction and it showed good high-rate discharge performances, about 140 mAh/g at 20 C rate . Various methods have also been reported to prepare nanosize LiFePO4 particles with micron/nanostructures, which are highly desired for designing high-performance lithium-ion batteries with high volumetric energy density and good rate capability [18-21]. These structured LiFePO4/C particles create 3D electronic and ionic pathways, which facilitate electron migration in the solid phase and lithium ion diffusion in the liquid phase and provide the material excellent cyclability and superior rate capability. These micron/submicron-sized LiFePO4 well-structured particles have a high tap density and, as electrodes, show excellent rate capability and cycle stability.
There is an urgent need for novel technologies that find cost-effective synthesis methods to produce micron/submicron-sized nanostructured LiFePO4 particles , which have a high capacity and, as electrodes, show excellent high rate capability, retention and cycle stability.

High performance cathode material LiFePO4, its precursors and methods of making thereof


A method for producing a letterpressed printed card includes letterpressing a design into card stock, to create a card shell. The card shell has a positive image of the letterpressed design debossed into a front face of the card. After letterpressing the design, an image is printed onto the card shell, to produce the letterpressed printed card.

Letterpress is a technique for applying a design to a card stock material. The letterpressed material is deformed such that the design is debossed into the material and depressed relative to the surrounding material. Letterpressing is performed by a letterpress machine. The machine presses the card stock material against a debossing plate. The design, which protrudes from the debossing plate, is pressed into the card stock. Before letterpressing the stock material, an image can be printed on the stock material by a printer.

Method for generating letterpressed products


A collecting bin for stacking sheets fed seriatem thereto, including an abutment associated with the front edges of the sheets in the area where a stapling device and a sheet-stack removal device are arranged. Above a sheet stack in the collecting bin and upstream of the stapling device, a rotatable shaft is mounted transversely to the sheet-feeding direction and parallel with the upper side of the sheet stack. The shaft is driven by a stepping motor in either direction of rotation. Separating fingers, arranged on the shaft, are selectively lowered onto the sheet stack by shaft rotation to form an inclined feeding surface for subsequently entering sheets, separating such subsequently fed sheets from the sheet stack beneath. When the sheet stack has been removed from the collecting bin, the shaft rotates in the opposite direction in order for separating fingers to deposit the separated sheets in the collecting bin. After the sheets have been deposited, the rotation of the shaft moves the separating fingers until they assume an initial position above the sheet stack.

This invention relates to apparatus for stacking sheets fed seriatem to a collecting bin where they are collected one on top of the other in a stack, the apparatus comprising a hold-back device which is arranged above the stack of sheets and in the area of the front edges of the stacked sheets and can be selectively introduced between the complete sheet stack and sheets subsequently fed to the stack.
In a sheet stacking apparatus disclosed in DE-PS No. 25 25 422, the sheets transported to a stacking point can temporarily be held back by a trapping device such that the sheet stack located underneath can be removed. For this purpose the trapping device comprises tongues which can be operated electromagnetically, each of which is associated with an electromagnet, which requires a great amount of components and a complex control in addition to a considerable amount of space.

Hold-back device for selectively separating sheets fed seriatem to a stack


A method for forming a semiconductor structure includes the following steps. Trenches are formed in a semiconductor region using a masking layer such that the trenches have a first depth, a first width along their bottom, and sidewalls having a first slope. The masking layer is removed, and a bevel etch is performed to taper the sidewalls of the trenches so that the sidewalls have a second slope less than the first slope.

The present invention relates in general to semiconductor technology, and more particularly to techniques for controlling the trench profile in semiconductor structures.
In many semiconductor structures, trenches of varying depths and widths that subsequently are partially or completely filled with various materials need to be formed. For example, in power device technology, trenches are formed for various purposes. In trench-gate power MOSFETs, trenches housing the gate electrode are formed; in shielded gate power MOSFETs, deeper trenches housing both a shield electrode and a gate electrode are formed; in yet other types of power devices which include what is commonly referred to as charge balance alternating p-n pillars structure, even deeper trenches are formed and subsequently filled with silicon material to form the alternating p-n pillars. In order to form the trenches in these structures, various silicon etch processes such as a dry etch process are used. However, as the critical dimensions (CD) continue to shrink, the width of the trenches is reduced while the depth of the trenches is not changed, or in some cases is increased. An aspect ratio of depth/width of the trenches is thus increased. The increasing aspect ratio of the trenches may adversely affect the filling of the trenches with such materials as gate polysilicon, epi material or dielectric material. Some common problems are formation of gaps, voids and/or defects in the filling material, which can adversely impact the device performance characteristics. Methods such as wet etch processes have been proposed to obtain trenches with wider upper portions, however, the wet etch process is an isotropic process and difficult to control.
Accordingly, there is a need for techniques which provide precise control over the trench profile, particularly for mid to high aspect ratio trenches.

Technique for controlling trench profile in semiconductor structures


An integrated circuit device comprising at least one analog to digital converter. The at least one ADC comprises at least one input operably coupled to at least one external contact of the integrated circuit device. The integrated circuit device further comprises detection circuitry comprising at least one detection module. The at least one detection module being arranged to receive at a first input thereof an indication of a voltage level at the at least one input of the at least one ADC, compare the received indication to a threshold value, and if the received indication exceeds the threshold value, output an indication that an excessive voltage state at the at least one input of the at least one ADC has been detected.

In the field of analogue to digital converters (ADCs), the accuracy of an ADC channel may be significantly impacted by an excessive pad voltage and, thus, an injection current. Such an excessive pad voltage may be caused by a short circuit or an Electrostatic Discharge (ESD) event, even if such an event occurs on an adjacent or nearby channel. Typically, excessive pad voltages and injection currents are limited by protection circuitry, such as ESD clamping diodes, external series resistors, etc. However, whilst such protection circuitry may be sufficient to provide a level of protection against damage caused by excessive pad voltages and injection currents, such protection circuitry is not capable of completely masking the effects of such events. Accordingly, when a fault condition, such as a short circuit to a supply voltage occurs, or an ESD event occurs, resulting in a larger than expected current being injected into an ADC pin, such an event will have a significant influence on the input signal of the ADC. In some instances, this affects the accuracy of the signal output by the ADC, despite the provision of protection circuitry. Furthermore, pads in close proximity to such an event, and particularly adjacent pads, may be affected by excessive voltage/injection current due to potential secondary effects of localised supply rail droop/surge.
ESD events, etc. tend to be of a short duration, and as such their effects typically dissipate relatively quickly, enabling normal operation of, in this scenario, the ADC to resume. However, corrupt output values from the ADC, as caused by an ESD event, etc., will have been provided to other circuitry such as, say, signal processing logic or the like, which rely on the values output by the ADC to perform their respective functions. Thus, the corrupt values provided by the ADC as a result of an ESD event or the like may cause inappropriate functioning of the system that relies on the values output by the ADC.

Integrated circuit device and method for detecting an excessive voltage state


An image processing device includes a processor, and a memory which stores an instruction, which when executed by the processor, causes the processor to execute an operation including obtaining an image including information on a traveling direction of a vehicle and information of side regions of the image relative to the traveling direction. The operation includes reducing a size of an arbitrary region of the image nonlinearly toward a center of the image from side ends of one of the regions of the image, extracting feature points from the arbitrary region, calculating traveling amounts of the feature points included in a plurality of arbitrary regions which are obtained at different timings and determining an approaching object which approaches the vehicle in accordance with the traveling amounts of the feature points.

In recent years, as a technique of supporting safe driving of automobiles, various techniques of displaying images of areas which are difficult to see by drivers and images of blind areas for the drivers have been proposed. In particular, since eyesight on right and left sides of vehicles is considerably narrow at T-junctions, such a supporting technique is particularly important. As the supporting technique, the following technique has been disclosed. That is, a plurality of cameras are disposed on a front end of a vehicle to capture images of right and left regions, and the images captured by the cameras are displayed in a display unit such as a car-mounted monitor. Furthermore, a technique for realizing early detection of an object, such as another vehicle or a pedestrian, which is approaching the own vehicle has also been proposed. For example, Japanese Laid-open Patent Publication No. 2005-276056 discusses a technique of capturing a plurality of images in a time series manner, extracting feature points from the images, comparing the feature points of the images with each other, associating feature points which have a high degree of correlation with each other, calculating optical flows, and detecting an approaching object. Note that such an approaching object detection function is included in a general navigation function. That is, one display unit has the approaching object detection function and the navigation function.

Image processing apparatus and image processing method


Seed coatings and methods of their use are described. The coatings comprise limestone or other water insoluble particulate matter which either includes a polymer in the limestone layer or a separate polymer coating on top of the limestone layer. The coatings may also include a coloring agent. The coatings offer the advantages of making the seed size more desirable and provide a more aesthetically pleasing appearance to the seeds.

Planting seeds is one of the most important methods of propagating many species of plants. Examples of plants which may be propagated from seeds include vines such as cucumbers, watermelons, and cantaloupes, flowers such as marigolds, zinnias, and pansies, cereals and small grains such as corn, wheat, oats, and barley, forage crops and grasses, such as alfalfa, lespedeza, clover, orchard grass, bluegrass and fescue, beans such as soybeans, string beans, pinto beans, navy beans and lima beans, peas such as English peas, chickpeas and black-eyed peas, and shrubbery and trees such as juniper, cedar, holly, pine, poplar and maple.
Normally, seeds are placed directly in the soil at the proper depth and spacing for the species being planted. Certain types of seeds, however, are extremely small which often makes planting difficult. These smaller seeds are also difficult to see which also adds to the difficulty of their planting. Examples of small seeds include alfalfa, celery and any type of grass seed.
Alfalfa seeds are much smaller than most seeds. Attempts to alleviate the problems associated with planting alfalfa seeds have included coating the seeds to make them larger and therefore easier to see and to plant. Seed coatings have also been used to house other ingredients to enhance seed propagation, such as pesticides, moldicides, fungicides, filler, and nutrients including nitrogen, potassium, and phosphorus.
The current industry standard for coating alfalfa seeds is to place the coating on the seed in an amount based on 33% of the weight of the seed. These coatings have been applied using a rotary drum method wherein the seed is tumbled while the coating composition is sprayed thereon and a stream of hot air is directed at the coated seeds. Other coating methods include pan-type arrangements, all of which are well known in the art.
There are several problems associated with these thick coatings. First, the coatings often do not stick to the seed well and can also chip and crack. This can cause the planters to get clogged or messy. Further, the thick coating impedes the rate of the flow of seeds in planters. This also leads to planter clogging.
It is therefore an object of the present invention to provide a seed coating to coat various types of seeds to make them easier to plant.
It is a further object of the present invention to provide a seed coating which does not clog or make a mess in planters.
It is a further object of the present invention to provide a seed coating which provides a seed size which is more acceptable to customers.
It is still a further object of the present invention to provide a seed coating which increases the size of seeds which would otherwise have to be discarded.
It is still a further object of the present invention to provide a thin seed coating for seeds that would be too large with the conventional coating and would otherwise have to be discarded.
It is yet another object of the present invention to provide a seed coating which allows seeds to flow easier through planters than conventionally coated seeds.
A further object of the present invention is to provide a seed coating which makes the seed easy to recognize and is aesthetically pleasing.
It is yet another object of the present invention to provide a seed coating which is economical to manufacture.
These and other objects of this invention are described more fully hereinafter.


A building management system (BMS) for filtering a fluid within a building is shown. The system includes one or more sensors configured to measure one or more characteristics of a first fluid within an air duct of the BMS and measure one or more characteristics of a second fluid after the second fluid has been filtered. The system further includes a pollutant management system configured to receive data from the one or more sensors and control a filtration process. The filtration process selects a filter of a plurality of filters based on a level of the one or more characteristics of the first fluid and the one or more characteristics of the second fluid.

Conventional methods for optimizing air quality within a building employ methods of using fixed ventilation rates to improve the quality of air. This can include ventilating the air in a constant process regardless of the change in outdoor air quality. In the event that air within a building may need to be optimized, conventional methods may rely on allowing more outdoor air to enter the building. This may not necessarily optimize the air quality, as the type of filtering, feedback system for various characteristics of outdoor air quality, and predictive modeling is not implemented and/or monitored.

Systems and methods for optimizing ventilation, filtration, and conditioning schemes for buildings


A method for fabricating a semiconductor device, includes forming a dielectric film above a substrate; forming an opening in the dielectric film; forming a first film containing a metal whose energy for forming silicide thereof is lower than that of Cu silicide inside the opening; forming a second film that is conductive and contains copper (Cu) in the opening in which the first film containing the metal is formed; and forming a compound film containing Cu and silicon (Si) selectively on the second film in an atmosphere in which a temperature of the substrate is below 300° C.

In recent years, with higher integration and higher performance of semiconductor integrated circuits (LSI), new micro-processing technologies have been developed. Recently, to achieve faster performance of LSI, there is particularly a trend to change wire materials from conventional aluminum (Al) alloys to copper (Cu) or Cu alloys (hereinafter, collectively referred to as Cu) having lower resistance. Since it is difficult to perform micro-processing on Cu by the dry etching method used frequently for forming an Al alloy wire, the so-called damascene method by which embedded wires are formed by depositing a Cu film on a dielectric film where a groove processing is performed and removing a portion of the Cu film that is not embedded in the grooves by the chemical mechanical polishing (CMP) is mainly adopted. Generally as the Cu film, a thin seed layer is formed by the sputter process or the like and then a laminated film of thickness of about several hundred nanometers are formed by electro-plating.
Here, when a multi-layer wire is formed by the damascene method or the like in a semiconductor integrated circuit (LSI), a metal cap film may be selectively formed on a Cu wire in order to prevent diffusion of Cu as a wire material into a low-k film in an upper layer as well as to increase adhesiveness to the low-k film. To achieve higher performance of multi-layer wires, the metal cap technology is expected to become necessary in the future. Major candidates of material of a metal cap film include a CuSiN film that is a compound film of Cu, silicon (Si), and nitrogen (N) or a CuSix film that is a silicide film of Cu (see Japanese Patent Application Laid-Open No. 2008-192739, for example). The CuSiN film or CuSix film has an effect of improving adhesiveness of the interface between a Cu wire and an inter-layer dielectric film of the upper layer and suppressing Cu atom transport in the interface between the Cu wire and inter-layer dielectric film. Accordingly, electro-migration (EM) characteristics are improved. However, if tantalum (Ta), which is generally used as a barrier metal (BM) of Cu wire, is used, the improvement factor of electro-migration characteristics is small to achieve only two to three times improvement in terms of the mean-time-to failure (MTF) compared with a case without the CuSiN film or CuSix film. Therefore, further improvement is needed.

Method for fabricating semiconductor device and semiconductor device


A transformer for converting 3 phase AC to 9 phase AC power is provided. The transformer includes first, second and third coils, each coil having a plurality of serial windings coupled together to form a polygon. The transformer further includes first, second and third input terminals each linked to a respective winding of the first, second and third coils. The input terminals are configured to receive a first, second and third phases of input AC power and at least one selected input terminal of the first, second and third input terminals is adjustable to alter a number of turns of the respective winding of the corresponding first, second or third coil on either side of the selected input terminal. The transformer further includes first through ninth output terminals linkable to first through ninth output power lines.

The present invention relates generally to power electronic devices such as those used in power conversion systems. More particularly, the present invention relates to transformers configured to convert 3 phase AC power to 9 phase AC power without the use of extra windings.
Multi-phase transformers are configured to convert a 3-phase AC input power to a multi-phase (e.g. 9 phase) AC output power. Such transformers are typically designed to provide a desired output AC power. The output AC power generated by the transformer may be rectified or filtered before being supplied to a load.
However, in some situations, the output voltage provided to the load is lower than the output power generated by the transformer due to losses in the output devices such as rectifiers, output filters and/or long cable lengths. One way to reduce such losses is to lower the cable resistance. However, such cables can increase the overall cost of a system.
Another technique to maintain the desired output power at a load is to include a step-up transformer to compensate for the output voltage drops. Typically, a buck or boost transformer is externally coupled to the multi-phase transformer. In some systems, an extra winding is added to the transformer. However, these approaches increase the overall cost and the size of the transformer.
Therefore, there is a need to design a multi-phase transformer that can operate as a step-up or step-down transformer without increasing the size or cost of the overall system.


A polyester resin composition exhibiting improved heat-resistant flexibility including (A) a polyester copolymer which is the polycondensation reaction product of (a) an aromatic dicarboxylic acid or an ester-forming derivative thereof, (b) an aliphatic glycol, and (c) between 0.001 to 1.0 mole %, based upon component (a), of a branch-forming compound, and (B) between 0.1 to 10% by weight (based on the total weight of the composition) of a bisoxazoline compound.

Polyalkylene terephthalate resins, such as polyethylene terephthalate or polybutylene terephthalate, have conventionally been used in applications requiring heat resistance. Moreover, polyalkylene terephthalate exhibits excellent mechanical and electrical properties, in addition to favorable processing characteristics. As such, polyalkylene terephthalate resins have been used in a number of diverse fields. Recently, however, the service and end-use environments for polyalkylene terephthalate resins have become more severe thereby creating a need for polyalkylene terephthalate resins of improved properties and/or performance characteristics.
Although polyalkylene terephthalate resins are considered to be "crystalline" resins, they nonetheless include a minor amount of non-crystalline regions. During use, particularly when the polyalkylene terephthalate is subjected to cyclical thermal history conditions (i.e. repeated cycles of high and low temperatures), the non-crystalline regions will crystallize. This crystallization will thereby change the resin's density and will, moreover, give rise to internal stress causing chain cleavage. Thus, the resin's mechanical properties, such as flexibility and impact resistance, are deleteriously reduced. For these reasons, the use of such resins in environments where the flexibility of the resin is important and where the resin is subject to repeated high/low temperature conditions, has been limited due to the adverse affect upon the resin's mechanical properties (i.e. flexibility) that such an environment could cause.
Attempts have been made to lower the crystallinity of polyester resin by the addition of an elastomer so as to address the above problem. However, polyester resin compositions containing an elastomer are disadvantageous in that long-term thermal history conditions cannot be tolerated -- presumably due to the crystalline matrix remaining in the resin. In addition, lower mechanical characteristics (such as abrasion resistance) are exhibited due to the reduced crystallinity of the resin, even though the addition of the elastomer gives some improvement.
What has been needed therefore is a polyalkylene terephthalate resin (e.g. a polyester) that does not lose its flexibility even when subjected to thermal history conditions and thus retains its excellent mechanical and electrical characteristics. It is towards attaining such a resin that the present invention is affected.
Broadly, the present invention is directed to resin compositions comprising an aromatic polyester copolymer having a branched or crosslinked structure and a specific compound (to be described below) that satisfies the above-noted requirements. More specifically, the present invention relates to polyester resin compositions which retain their flexibility even when subjected to cyclic thermal conditions, and comprise, (A) a polyester copolymer prepared by the polycondensation of (a) an aromatic dicarboxylic acid or an ester-forming derivative thereof with (b) an aliphatic glycol and (c) a branch-forming compound wherein said branch-forming compound (c) is contained in an amount of 0.001 to 1.0 mole % based on the component (a), and (B) 0.1 to 10% by weight (based on the total weight of the composition) of a bisoxazoline compound.
Until the present invention, it has been very difficult to provide a polyester resin composition that simultaneously exhibits a number of desirable characteristics, for example, abrasion resistance and flexibility (flexing properties and elongation), together with an ability to retain its initial high elongation and flexing properties for prolonged time periods in heated atmospheres. Accordingly, it is unexpected that compositions comprising a polyalkylene terephthalate containing a branched or crosslinked structure, and a bisoxazoline compound (within a specified ratio) according to the present invention do not lose their flexibility even when subjected to thermal history conditions and, in addition, exhibit significantly improved long-term stability in heated atmospheres.


Disclosed is a process for the enantioselective production of an optically active amino compound by the amination of the Cxe2x80x94H bond of an organic compound. The amino compound is produced by converting the Cxe2x80x94H bond at the allyl position of an alkene or the Cxe2x80x94H bond at the benzyl position of an alkylarene to the corresponding Cxe2x80x94N bond, using a salen-manganese complex as the catalyst and N-substituted iminoaryliodinane as the amination agent. Both the catalytic activity and the enantioselectivity are very high when there is used a catalyst in which the 3- and 5-positions of the salicylaldehyde moiety of the salen ligand are substituted with an electron-withdrawing group, particularly with a halogen atom.

The present invention relates to a novel process for producing amino compounds, and particularly to a process for producing amino compounds by enantioselectively converting Cxe2x80x94H bonds at the allyl positions of alkenes or at the benzyl positions of aklylarenes, to the corresponding Cxe2x80x94N bonds.
The amination of Cxe2x80x94H bonds of organic compounds is one of the most useful techniques in synthetic chemistry, particularly because a number of compounds having amino groups exhibit physiological activities that make them important as medicinal or agricultural materials and their intermediates.
However, reactions applicable to the amination of Cxe2x80x94H bonds are actually very few. Only a small number of amination reactions have been proposed for the Cxe2x80x94H amination using complexes of metals with porphyrin, cyclic amines or bipyridine as catalysts. Another such reaction is the one proposed by the present inventors, in which the amination reaction of Cxe2x80x94H bonds proceeds under Kharash-Sosnovsky conditions using a copper catalyst (Japanese Patent Application Publication No. 140044/1998). However, these reactions are all directed to the preparation of simple amino compounds and none are for producing optically active aminocompounds. While some asymmetric syntheses have been proposed for preparing optically active compounds through the amination of Cxe2x80x94H bonds using metal complexes as catalysts, the enantioselectivities are low, generally on the order of 20 to 30% at most.
It is a primary object of the present invention to provide a new process for the amination of Cxe2x80x94H bonds of organic compounds, particularly to provide a process by which optically active amino compounds can be produced in an enantioselective manner by the amination of the Cxe2x80x94H bonds.
After extensive studies the present inventors have now discovered that the utilization of specific salen-metal complexes as catalysts enables a highly enantioselective amination of Cxe2x80x94H bonds at allyl positions of alkenes or at benzyl positions of alkylarenes and established a new process that achieves the above-mentioned object.
Thus, according to the present invention there is provided a process for producing an amino compound from an alkene or from an alkylarene, which comprises converting the Cxe2x80x94H bond at the allyl position of the alkene or the Cxe2x80x94H bond at the benzyl position of the alkylarene, to the Cxe2x80x94N bond, wherein there are used an optically active salen-manganese complex as the catalyst and a N-substituted iminoaryliodinane as the amination agent.
In a preferred embodiment of the present invention, the optically active salen-manganese complex is one expressed by formula (1):
In the formula (1), at least one of R1 and R2 denotes an electron-withdrawing group, and R3 denotes an alkyl group, having 1 to 4 carbon atoms or phenyl group, which may be a substituted one, or the two R3xe2x80x2s are linked together to form a five- to seven-membered alicyclic hydrocarbon group.
In a more preferred embodiment of the present invention, the electron-withdrawing group is a halogen atom, preferably bromine, and the amination agent is N-(p-toluenesulfonyl) iminophenyliodinane.

Process for preparing amino compounds by using salen-manganese complexes as the catalyst

Japan Science and Technology Corporation


An electronic device includes a body, a rotatable member, a projecting unit configured for projecting an image, a sensing unit and a processing unit. The body includes a connecting end, and a plurality of conductive contacts is formed at the connecting end. The rotatable member is rotatably connected to the connecting end. The rotating member includes a conductive ball configured for being electrically connected to one of the plurality of the conductive contacts, and the plurality of conductive contacts are formed along a displacement path of the conductive ball. The sensing unit is configured for sensing interactions at specific locations corresponding to the projected image. The processing unit stores a plurality of images, and is configured for controlling the projecting unit to project a corresponding image according to the conductive contact which is electrically connected to the conductive ball.

1. Technical Field
The present disclosure relates to electronic devices, and particularly, to an electronic device with a virtual keyboard function.
2. Description of Related Art
A virtual keyboard technology has been developed. Electronic devices, such as cell phones, with the virtual keyboard technology can project a virtual keyboard (image) onto a surface and detect a keystroke on the virtual keyboard by detecting interactions at specific locations on the projected image. However, most virtual keyboard projectors are separate from the electronic device and each application of the electronic device may adopt a different input device other than the virtual keyboard. This is an inconvenience.
Therefore, what is needed is to provide an electronic device, in which the above problem is eliminated or at least alleviated.

Electronic device with virtual keyboard function

Hong Fu Jin Precision Industry (ShenZhen) Co., Ltd.


An apparatus and method of controlling a vehicle aftertreatment system is provided. The aftertreatment system treats exhaust gas produced by the vehicle engine and includes a particulate filter, and a NOx reducing device such as a selective catalytic reduction (SCR) device. The particulate filter is configured to regenerate to remove accumulated particles when the exhaust gas is heated above a regeneration temperature. A diagnostic device is included for monitoring the aftertreatment system. The diagnostic device may be a sensor for measuring the oxides of nitrogen (NOx) and/or an SCR efficiency monitor. A controller is employed to optimize the function of the diagnostic device. The controller does not enable the diagnostic device when the vehicle is powered until one or more entry conditions are satisfied.

Internal combustion engines produce a number of emissions, including various oxides of nitrogen, referred to collectively herein as NOx gases. NOx gases are created when nitrogen and oxygen molecules present in engine intake air are exposed to high temperatures of combustion. Exhaust aftertreatment systems are used in vehicles in order to reduce and manage the NOx gases created in the combustion process. To aid this process, aftertreatment systems employ a variety of diagnostic devices.

Exhaust aftertreatment system with diagnostic delay


An imaging control apparatus inputs an image signal from an image sensing unit, controls, based on a first image signal from the image sensing unit for a first region, a mechanical component which controls an aperture for image sensing by the image sensing unit, and electronically controls, based on the first image signal and a second image signal from the image sensing unit for a second region, the image luminance represented by an output from the image sensing unit for the second region.

1. Field of the Invention
The present invention relates to an imaging control apparatus, imaging control method, and computer-readable storage medium.
2. Description of the Related Art
There has been proposed a technique which extracts a plurality of regions from one sensed image, performs processes such as luminance correction in each region, and composites the regions into one image, thereby obtaining appropriate exposure in the overall image and each extracted image (U.S. Patent Publication No. 2005/093886).
Another proposed technique obtains exposure in an entire image by performing weighted averaging for the photometric value of each divided image and deriving the photometric value of the overall image (Japanese Patent Laid-Open No. 2002-320137). Still another technique has also been proposed which suppresses the level of a signal at a predetermined level or more in an image, thereby obtaining an image in appropriate exposure even in a partial region (Japanese Patent Laid-Open No. 60-242776).
However, the above-described techniques have various problems. For example, the technique described in U.S. Patent Publication No. 2005/093886 puts a load on the extraction and compositing processes, and a real-time process is difficult. Even if the real-time process is possible, the process load is enormous. The technique described in Japanese Patent Laid-Open No. 2002-320137 obtains only the exposure value of the entire image but no optimum image in each partial region. The technique described in Japanese Patent Laid-Open No. 60-242776 cannot obtain an image in appropriate exposure in each designed partial region.

Imaging control apparatus, imaging control method, and computer-readable storage medium