By immobilizing identical or different nucleic acids in a plurality of dot-like areas on a carrier which comprises a base material and compound carried on the base material, the compound having one or more alkylating groups, through intermediary of the alkylating group, a nucleic acid-immobilized substrate on which nucleic acids are firmly immobilized in fine dot area without reference to chain length of nucleic acids is provided, which enables efficiently introducing the nucleic acids onto the base material in a simple manner and can be produced with a simple apparatus.

1. Field of the Invention
The present invention relates to a nucleic acid-immobilized substrate. More particularly, it relates to a nucleic acid-immobilized substrate that can efficiently immobilize nucleic acids on a carrier in a simple manner as well as a production method therefor and an analysis method by utilizing it.
2. Description of the Related Art
As the method for producing nucleic acid-immobilized substrates comprising a carrier on which nucleic acids and so forth are immobilized, which are used for DNA tips and so forth, the following two kinds of methods are mainly used:
(1) a method of immobilizing nucleic acids by physical adsorption using a base material coated with poly-L-lysine etc. as a carrier (International Patent Publication in Japanese (Kohyo) No. 10-503841/1998), and
(2) a method of synthesizing DNA on a base material (WO97/10365).
Among the aforementioned methods, however, the method described in International Patent Publication in Japanese No. 10-503841/1998 has a drawback that if hybridization is performed by using this method, nucleic acids are dropped off from the substrate especially during operational steps, and consequently detection sensitivity may be reduced and results may be varied to cause bad reproducibility. Furthermore, this method also suffers from a drawback that a short chain nucleic acid of about 50-mer or less such as oligomers cannot be efficiently immobilized, although a long chain nucleic acid can be immobilized by this method.
Further, the method described in WO97/10365 requires an extremely special apparatus and extremely special regents, because DNA is synthesized on a base material. Thus, it is not a method that can be easily performed by anyone. Moreover, it also suffers from a drawback that nucleic acids that can be synthesized are limited to those of about 25-mer or shorter.
The present invention was accomplished in view of the aforementioned problems, and its object is to provide a nucleic acid-immobilized substrate on which nucleic acids are firmly immobilized in fine dot areas without reference to chain length of the nucleic acids, which enables efficiently introducing the nucleic acids onto a base material in a simple manner and can be produced with a simple apparatus.
The inventors of the present invention found that if nucleic acids are immobilized on a carrier that comprises a base material carrying compound having one or more alkylating groups through the intermediary of the alkylating group, the nucleic acids can firmly be immobilized on the carrier in fine dot areas without reference to chain length of the nucleic acids, and the aforementioned object can be achieved. Thus, they accomplished the present invention.
That is, the present invention provides the followings.
(1) A nucleic acid-immobilized substrate having a carrier and identical or different nucleic acids,
wherein the carrier comprises a base material and compound on the base material, the compound having one or more alkylating groups, and the nucleic acids are immobilized in a plurality of dot-like areas on the carrier through the intermediary of the alkylating group.
(2) The nucleic acid-immobilized substrate according to (1), wherein the compound having the alkylating groups consists of nitrogen yperite.
(3) The nucleic acid-immobilized substrate according to (1) or (2), wherein the carrier has a structure represented by the following general formula (I):
Mxe2x80x94Rnxe2x80x94Gxe2x80x83xe2x80x83(I)
[In the formula, M represents the compound having one or more alkylating groups;
R represents a functional group selected from the group consisting of xe2x80x94NHxe2x80x94, xe2x80x94CH2xe2x80x94, xe2x80x94NHCOxe2x80x94, xe2x80x94CONHxe2x80x94, xe2x80x94Oxe2x80x94, xe2x80x94Sxe2x80x94, xe2x80x94N(R1)xe2x80x94 (R1 represents a normal, cyclic, or branched saturated aliphatic hydrocarbon group having 1-20 carbon atoms or unsaturated aliphatic hydrocarbon group having 1-20 carbon atoms),
(R2 and R3 independently represent a hydrogen atom, a normal or branched saturated aliphatic hydrocarbon group having 1-20 carbon atoms or unsaturated aliphatic hydrocarbon group having 1-20 carbon atoms, a cycloalkyl group, an aryl group or an aralkyl group, which may have one or more substituents; provided that one of R2 and R3 represents a hydrogen atom, the other represents a normal or branched saturated aliphatic hydrocarbon group having 1-20 carbon atoms or unsaturated aliphatic hydrocarbon group having 1-20 carbon atoms, a cycloalkyl group, an aryl group or an aralkyl group, which may have one or more substituents; R2 and R3 may be also bonded together to form a nitrogen-containing heterocyclic group that may contain an oxygen atom), xe2x80x94COOxe2x80x94, xe2x80x94OCOxe2x80x94, xe2x80x94NHSO2xe2x80x94, xe2x80x94NHC(S)NHxe2x80x94 and xe2x80x94SO2NHxe2x80x94;
n represents an integer of 0-20;
when two or more groups of R exist, they may be identical to or different from each other;
G represents the base material or a polymer that can be adhered to the base material].
(4) A carrier for immobilizing nucleic acids, which comprises a base material and compound carried on the base material, the compound having one or more alkylating groups.
(5) A method for producing a carrier for immobilizing nucleic acids, the carrier comprising a base material and compound carried on the base material, the compound having one or more alkylating groups,
which comprises the step of getting the compound having two or more alkylating groups or the compound having one or more alkylating groups and one or more functional groups that are not alkylating groups, to covalently bond with functional groups on a surface of the base material having the functional groups can be covalently bonded with the alkylating groups or with the functional groups that are not alkylating groups,
while leaving at least one of the alkylating groups of the compound.
(6) A method for producing a nucleic acid-immobilized substrate, which comprises the step of bringing nucleic acids into contact with a carrier for immobilizing nucleic acids,
wherein the carrier comprises a base material and compound carried on the base material, the compound having one or more alkylating groups.
(7) A method for detecting a nucleic acid by hybridization using a nucleic acid labeled with a labeling substance,
wherein the nucleic acid-immobilized substrate according to any one of (1) to (3) is used.
Hereafter, embodiments of the present invention will be explained in detail.
 less than 1 greater than  Carrier
The carrier used for the nucleic acid-immobilized substrate of the present invention is for immobilizing nucleic acids, and comprises a base material and compound carried on the base material, the compound having one or more alkylating groups (this may also be referred to as xe2x80x9calkylating reagentxe2x80x9d hereafter).
(1) Base material
The base material used for the present invention serves as a support of the aforementioned carrier, and it is not particularly limited so long as it basically composed of a material that is insoluble in a solvent and is in a state of solid or gel at an ordinary temperature or within a temperature range around it (0-100xc2x0 C.). The definition that the base material is insoluble in a solvent means that the base material is substantially insoluble in various aqueous and organic solvents used for process steps where the alkylating reagent is provided on the base material to be carried on the base material as described hereinafter, then nucleic acids are immobilized thereon as the carrier, and then the substrate is used as a DNA tip or the like.
Specific examples of the material of the carrier base material include plastics, inorganic polymers, metals, natural polymers, ceramics and so forth.
Specific examples of the plastics include polyethylene, polystyrene, polycarbonate, polypropylene, polyamide, phenol resin, epoxy resin, polycarbodiimide resin, polyvinyl chloride, polyvinylidene fluoride, fluorinated polyethylene, polyimide, acrylic resin and so forth. Specific examples of the inorganic polymers include glass, crystal, carbon, silica gel, graphite and so forth. Specific examples of the metals include gold, platinum, silver, copper, iron, aluminum, magnet, paramagnet, apatite and so forth. Examples of the natural polymers include cellulose, chitin, chitosan, alginic acid, derivatives thereof and so forth. Specific examples of the ceramics include alumina, silica, silicon carbide, silicon nitride, boron carbide and so forth.
The aforementioned base material may be in the form of, for example, a film, plate, fiber or the like, and its size is not particularly limited.
(2) Compound having one or more alkylating groups
The alkylating group used for the present invention refers to a group that introduces an alkyl group into another compound through a substitution reaction or addition reaction. The compound having such one or more alkylating groups is one used as an alkylating reagent, and examples thereof include alkyl halide, dialkyl sulfate, aromatic sulfonic acid alkyl ester, alkyl metal compound and so forth.
As such an alkylating reagent, nitrogen yperites can be preferably used. Nitrogen yperites can be produced by the methods disclosed in U.S. Pat. Nos. 2,141,090, 5,273,991, 5,387,707 and so forth.
Specific examples of the nitrogen yperites include halogenated alkyl-N-alkylaminobenzene, dihalogenated alkyl-N-aminobenzene, halogenated alkoxy-N-alkylaminobenzene, dihalogenated alkoxy-N-aminobenzene, halogenated alkyl-N-alkoxyaminobenzene, halogenated alkoxy-N-alkoxyaminobenzene, halogenated alkylphenylaminobenzene, halogenated alkoxy-N-sulfonylalkylbenzene, halogenated alkyl-N-sulfonylalkoxyaminobenzene, halogenated alkyl-N-carboxyalkylaminobenzene, halogenated alkoxy-N-carboxyalkylaminobenzene, halogenated alkoxy-N-carboxyalkoxyaminobenzene and so forth.
The aforementioned nitrogen yperites may have another functional group or atom as a substituent, so that they can covalently bond with the base material or with a polymer compound for physically immobilizing the alkylating group to the base material. Specific examples of such a substituent include, for example, functional groups such as hydroxyl group, halogen atom, halogenated alkyl group, halogenated acyl group, halogenated allyl group, acyl group, allyl group, carboxyl group, sulfoxyl group, phosphonium group, ketone, aldehyde, isocyanate group, isothiocyanate group, carbodiimide group, thiol group and amino group.
The position of the aforementioned substituent may be any position that does not inhibit the alkylation reaction by the nitrogen yperite. Specifically, it may be at a position other than the position of the alkylating group that participates in the alkylation reaction and the position on the tertiary nitrogen atom. The substituent is preferably introduced on an aromatic ring.
(3) Carrier
The carrier for immobilizing nucleic acids used for the present invention comprises the aforementioned base material and the aforementioned alkylating reagent carried on the base material. The term xe2x80x9ccarryxe2x80x9d used for the present invention means that the alkylating reagent is not substantially dropped off from the base material in various solvents such as water-soluble solvents and organic solvents used when the nucleic acids are immobilized on the carrier, when the nucleic acid-immobilized substrate is used as a DNA tip etc, or the like.
As for the carrier used for the present invention, the aforementioned alkylating reagent may be carried simply by utilizing physical adhesion, or may be chemically carried through covalent bond, so long as it is carried on the aforementioned base material. However, in the carrier used for the present invention, the alkylating reagent is preferably carried on the base material through covalent bond.
Further, the alkylating reagent may be carried on the whole surface of the base material or on a part thereof, as required.
When the aforementioned alkylating reagent is carried on the base material by physical adhesion, compound comprising a polymer compound and the alkylating reagent bonded with the polymer compound through covalent bond can be used, which may also be referred to as xe2x80x9calkylating reagent carrying polymer compoundxe2x80x9d hereafter. Although the alkylating reagent carrying polymer compound is not particularly limited so long as it is compound comprising the alkylating reagent bonded with the polymer compound, the alkylating reagent carrying polymer compound preferably has a molecular weight in the range of 500 to 1,000,000.
The alkylating reagent carrying polymer compound carried on the base material by physical adhesion preferably has 2 to 2000 alkylating reagent molecules in the polymer molecule irrespective of the type thereof. If the number of the alkylating reagent molecules in which the alkykating reagent carrying polymer compound has, is less than 2, i.e., 1, it lacks the ability to immobilize nucleic acids. To the contrary, the number of the alkylating reagent molecules is too mach larger than the aforementioned range, its viscosity may become to high or it may not be made into a solution, and thus its handling property may be degraded when it is applied to the base material, although it may not show unsatisfactory performance as a product.
Such an alkylating reagent carrying polymer compound shows high adhesion to the aforementioned base material, and it is carried on the base material by this adhesion. A typical form of the alkylating reagent carrying polymer compound carried on the base material by physical adhesion is a coated film.
The method for obtaining the aforementioned alkylating reagent carrying polymer compound carried on the base material in the form of a coated film may be a known method, for example, spraying, immersing, brushing, stamping, vapor deposition, coating by using a film coater and so forth.
Now, the carrier carrying the alkylating reagent through covalent bond will be explained.
The alkylating reagent to be carried through covalent bond may be any one of the aforementioned ones. The alkylating reagent which the carrier has on the base material through covalent bond, preferably has 3 to 300 alkylating groups in the molecule. If the number of the alkylating groups is 3 to 300, sufficient ability to immobilize nucleic acids can be obtained, and its solution may have an appropriate viscosity and thus preferred in view of handling thereof.
To obtain a carrier carrying the aforementioned compound having the alkylating group(s) through covalent bond on the surface of the base material, which may also be referred to as xe2x80x9ccovalent bond type carrierxe2x80x9d hereafter, for example, an alkylating reagent having one ore more alkylating groups for immobilizing nucleic acids when it is used in a carrier and further having one or more functional groups for forming covalent bond with the base material surface can be covalently bonded with functional groups of the base material having, on its surface, functional groups that can be covalently bonded with the functional groups of the alkylating reagent by a suitable method.
More specifically, the covalent bond type carrier can be obtained by, for example, getting compound having two or more alkylating groups, or compound having one or more alkylating groups and one or more functional groups that are not alkylating groups, to covalently bond with the functional groups on the surface of the base material having functional groups that can be covalently bonded with the alkylating groups or with the functional groups that are not alkylating groups, while leaving at least one of the alkylating groups of the compound.
As the compound having two or more alkylating groups or the compound having one or more alkylating groups and one or more functional groups that are not alkylating groups used for the production of the carrier that can be covalently bonded with the alkylating reagent, there can be specifically mentioned compound having two or more alkylating groups and compound having one or more alkylating groups and one or more functional groups that are not alkylating groups among the alkylating reagents mentioned in the above (2). Further, it is also possible to utilize compound consisting of any one of the alkylating reagents mentioned in the above (2) introduced with the aforementioned functional groups for providing the covalent bond by a suitable method for the production of the aforementioned covalent bond type carrier. Furthermore, it is also possible to utilize compound consisting of any one of the alkylating reagents mentioned in the above (2) further introduced with the alkylating groups as the functional groups for providing the covalent bond for the production of the aforementioned covalent bond type carrier. The method for introducing such the functional groups into the alkylating reagent may be a conventionally known method.
The position at which the functional group for providing the covalent bond is introduced is not particularly limited, so long as the alkylation reaction by the alkylation regent is not inhibited. However, the functional group is preferably introduced on an aromatic ring, when the aforementioned alkylating reagent is a nitrogen yperite.
As the base material having on its surface functional groups that can be covalently bonded with the alkylating groups or with the functional groups that are not the alkylating groups, which is possessed by the aforementioned compound, there can be mentioned, for example, the base material explained in the above (1) introduced with the functional groups that can provide covalent bond on its surface. The functional group to be introduced is not particularly limited so long as it is a functional group that can be covalently bonded with the alkylating reagent or a functional group that can be covalently bonded with the functional group other than the alkylating group. Specific examples thereof include hydroxyl group, imino group, amino group, carboxyl group, carbodiimide group, aldehyde group and so forth. These functional groups can suitably be selected depending on the functional groups of the aforementioned alkylating reagent, which forms covalent bond, and introduced onto the base material surface.
As for the method for introducing such functional groups onto the base material surface, a suitable method can be selected depending on the material of the base material, the functional group to be introduced and so forth. Furthermore, the functional group may be introduced onto the whole surface of the base material or onto a part thereof.
When amino groups are introduced onto the whole surface of a glass base material, for example, the glass base material can be immersed in a solution prepared by dissolving an amino-substituted organoalkoxysilane such as 3-aminopropyltriethoxysilane in a suitable solvent for about 2 to 3 hours under a temperature condition of 70 to 80xc2x0 C. Then, the base material may be taken out from the solution, washed with water to remove the solution, and dried by heating at about 100-120xc2x0 C. for about 4 to 5 hours. Further, it is also possible to allow the amino group of the aforementioned 3-aminopropyltriethoxysilane and the functional group other than the alkylating group of the alkylating reagent to react with each other using a suitable solvent so that the alkylating reagent should be directly introduced onto the surface of the glass base material.
As also for the cases where functional groups other than amino group are introduced onto a glass substrate or where functional groups are introduced onto a substrate made of a material other than glass, it is a commonly used conventional technique that various functional groups are introduced onto surfaces of the various materials mentioned in the above explanation of the base material, and methods therefor are known. Therefore, also in such cases, functional groups can be introduced onto the surface of base material by using such known methods.
Furthermore, the base materials mentioned in the above (1) include those plastic base materials that already have such functional groups as mentioned above on the base material surfaces. In such a case, those materials can be used as they are for the production of the aforementioned covalent bond type carrier without introducing the functional groups onto the base material surfaces. Further, such plastic base materials may also be used for the production of the carrier after functional groups are further introduced onto them.
In order to produce the covalent bond type carrier used for the present invention, compound having two or more alkylating groups or compound having one or more alkylating groups and one or more functional groups that are not alkylating groups, and a base material having on its surface functional groups that can be covalently bonded with the alkylating groups or with the functional groups that are not alkylating groups, are allowed to react under a suitable condition, so that the compound should be covalently bonded with the functional groups on the surface of the base material, while leaving at least one alkylating group of the compound. That is, when the compound is compound having one or more alkylating groups and one or more functional groups that are not alkylating groups, the reaction can be performed under such a condition that the functional groups that are not alkylating groups should form covalent bond. Further, when compound having only the alkylating groups is used, the reaction can be performed under such a condition that all of the alkylating groups should not form covalent bond.
The carrier for immobilizing nucleic acids obtained as described above, which comprises the base material and the compound having alkylating groups carried on the base material, can firmly immobilize nucleic acids of various kinds and sizes by utilizing the reactivity of the alkylating groups of the compound having alkylating groups.
Specifically, the carrier used for the nucleic acid-immobilized substrate of the present invention preferably has a structure represented by the following general formula (i):
M-Rn-Gxe2x80x83xe2x80x83(i)
In the formula (i), M represents the aforementioned compound having the alkylating group, and actually a group having covalent bond portion for bonding with the aforementioned base material or polymer compound. As described above, the covalent bond is preferably present on an aromatic ring, when the compound having an alkylating group is a nitrogen yperite.
R represents a divalent functional group selected from xe2x80x94NHxe2x80x94, xe2x80x94CH2xe2x80x94, xe2x80x94NHCOxe2x80x94, xe2x80x94CONHxe2x80x94, xe2x80x94Oxe2x80x94, xe2x80x94Sxe2x80x94, xe2x80x94N(R1)xe2x80x94 (R1 represents a normal, cyclic, or branched saturated aliphatic hydrocarbon group having 1-20 carbon atoms or unsaturated aliphatic hydrocarbon group having 1-20 carbon atoms),
(R2 and R3 independently represent a hydrogen atom, a normal or branched saturated aliphatic hydrocarbon group having 1-20 carbon atoms or unsaturated aliphatic hydrocarbon group having 1-20 carbon atoms, a cycloalkyl group, an aryl group or an aralkyl group, which may have one or more substituents. However, if one of R2 and R3 represents a hydrogen atom, the other represents a normal or branched saturated aliphatic hydrocarbon group having 1-20 carbon atoms or unsaturated aliphatic hydrocarbon group having 1-20 carbon atoms, a cycloalkyl group, an aryl group or an aralkyl group, which may have one or more substituents. Alternatively, R2 and R3 may be bonded together to form a nitrogen-containing heterocyclic group that may contain an oxygen atom), xe2x80x94COOxe2x80x94, xe2x80x94OCOxe2x80x94, xe2x80x94NHSO2xe2x80x94, xe2x80x94NHC(S)NHxe2x80x94, xe2x80x94SO2NHxe2x80x94 and so forth. n represents an integer of 0-20. When R consists of two or more groups, they may be identical to or different from each other.
R is a group formed as a result of covalent bond between an alkyl group or a functional group other than alkyl group of the aforementioned compound having two or more alkylating groups or having one or more alkylating groups and one or more functional groups that are not alkylating groups, and a functional group of the aforementioned base material having functional groups that can be covalently bonded with the alkylating group or with the functional group other than the alkylating group. R may contain one or more other functional groups introduced beforehand into the alkylating reagent or one or more other functional groups introduced into the base material, which are not directly involved in the aforementioned covalent bond.
G represents the base material or the polymer compound. When the aforementioned alkylating reagent is carried on the base material through physical adhesion, G represents the polymer compound, and this polymer compound is adhered to the base material to form a carrier.
 less than 2 greater than  Nucleic acid-immobilized substrate
In the nucleic acid-immobilized substrate of the present invention, identical or different nucleic acids are immobilized in a plurality of dot-like areas on the carrier that comprises the base material and the alkylating reagent carried on the base material through the intermediary of the alkylating group.
In the nucleic acid-immobilized substrate of the present invention, the definition that nucleic acids are immobilized on dot-like areas means that the areas on which the nucleic acids are immobilized are sufficiently smaller than the size of the carrier in such a degree that a plurality of the nucleic acid-immobilized sites can be provided. The shape of the dots is not particularly limited, and arbitrarily selected depending on the way of use, purpose of use and so forth of the nucleic acid-immobilized substrate.
The dot-like nucleic acid immobilized sites of the nucleic acid-immobilized substrate of the present invention are specifically, for example, those having an approximately circular shape and having a diameter of 10-3000 xcexcm. As for the size of the dots, the diameter is more preferably about 50-2000 xcexcm, further preferably about 100-1500 xcexcm. The term xe2x80x9capproximately circular shapexe2x80x9d means that the shape is not limited to a round but includes shapes analogous to a circle such as oval shapes without any particular limitation. The diameter of oval shape, for example, means an average value of the major axis and the minor axis.
As for the size of the dots mentioned above, if the diameter is less than 10 xcexcm, detection may become difficult, whereas if the diameter exceeds 3000 xcexcm, it may become difficult to secure a moderate number of dots per unit area. Therefore, if it takes into consideration ease of detection, provision of desired number of the dots per unit area and so forth, it is preferable to make the size of the dots within the aforementioned range.
The number of the dot-like nucleic acid-immobilized sites of the nucleic acid-immobilized substrate of the present invention is not particularly limited, and suitably selected depending on the way of use, purpose of use and so forth of the nucleic acid-immobilized substrate. However, for example, the number of the nucleic acid-immobilized sites may be, specifically, about 10-10000, preferably about 50-350, per 1 cm2 of the nucleic acid-immobilized substrate. The geometrical arrangement of the dot-like nucleic acid-immobilized sites of the nucleic acid-immobilized substrate of the present invention may also be suitably selected depending on the way of use, purpose of use and so forth of the nucleic acid-immobilized substrate.
As the nucleic acids to be immobilized on the nucleic acid-immobilized substrate of the present invention, there can be mentioned natural DNA or synthesized DNA (including oligo nucleotides) and RNA (including oligo nucleotides) without any particular limitation. The nucleic acids to be immobilized may be single-stranded or double stranded. According to the present invention, nucleic acids that have a functional group showing reactivity with the alkylating group, are usually used as the aforementioned nucleic acids. The nucleic acids immobilized in dot-like areas of the nucleic acid-immobilized substrate of the present invention may be identical or different from each other. When different nucleic acids are used, geometrical arrangement of those nucleic acids and so forth may suitably be selected depending on the way of use, purpose of use and so forth of the nucleic acid-immobilized substrate to be obtained.
To immobilize such nucleic acids in dot-like shapes on the carrier, small amounts of nucleic acids can be provided in dot-like shape of a desired size on portions of the base material that carries the alkylating reagent under a suitable condition so that the alkylating reagent and the nucleic acids should be brought into contact with each other to cause the reaction between them. As a result of the reaction of the alkylating group of the alkylating reagent carried on the base material, and amino group, imino group or the like of the nucleic acids, the nucleic acids are covalently bonded with the alkylating reagent. If thiol groups are introduced into the nucleic acids beforehand, covalent bond is also formed by reaction of the aforementioned alkylating group and the thiol group. As a result, the nucleic acids are immobilized on the carrier.
Specifically, nucleic acids are usually provided in a state that they are contained in water or buffer so that the activity of the nucleic acids to be immobilized should be maintained during the contact and the reaction of the both. In general, the temperature for the contact is preferably 0-100xc2x0 C. so that the activity of the nucleic acids to be immobilized should not be lost.
Means for providing small amounts of nucleic acids, usually in the form of water or buffer containing the nucleic acids, in dot-like areas on the carrier includes method of utilizing a dispenser, method of utilizing a pin, method of utilizing bubble jet and so forth. However, the present invention is not limited to these. Apparatuses for providing solutions in small amounts by the above methods are commercially available, and they can be used for the present invention.
When analysis is carried out by using the nucleic acid-immobilized substrate of the present invention, the nucleic acid-immobilized substrate is frequently brought into contact with nucleic acids other than the aforementioned immobilized nucleic acids and so forth. Therefore, in order to prevent nucleic acids other than the immobilized nucleic acids and so forth from non-specifically bonding with unreacted alkylating groups of the alkylating reagent carried on the carrier, after the nucleic acids are immobilized in dot-like areas on the carrier as described above, free alkylating groups are preferably blocked by bringing them into contact with an excessive amount of bovine serum albumin (BSA), casein, salmon sperm DNA or the like.
In the nucleic acid-immobilized substrate of the present invention obtained as described above, the nucleic acids are very firmly carried on the carrier, and they are not released even by washing methods widely used for hybridization and so forth (washing methods using surface active agents). If analysis is carried out by using the nucleic acid-immobilized substrate, the analysis can be performed with superior reproducibility and quantification ability. Further, since the nucleic acid-immobilized substrate of the present invention can immobilize nucleic acids without reference to the number and length of the chains, various nucleic acids can be simultaneously dealt with on the same substrate. Based on these, the nucleic acid-immobilized substrate of the present invention can be used as a DNA tip and so forth for techniques of determining nucleotide sequences by hybridization using a large number of nucleic acids, for example, SBH (Sequencing by Hybridization) method, SHOM (Sequencing by Hybridization with Oligonucleotide Matrix) method and so forth with superior performance.


The present invention relates to a liquid crystal compound which has negative dielectric anisotropy and a large absolute value thereof; and a liquid crystal display element which contains the compound as a constituent element and has a negative value of dielectric anisotropy in the vertical alignment mode, IPS, or the like. The liquid-crystal display element has a structure including a pair of substrates and a liquid crystal sandwiched therebetween, and includes at least an alignment control layer, a transparent electrode, and a polarizing plate, in which the liquid crystal includes at least one compound having a partial structure represented by general formula (A):

At present, liquid crystal display elements are now widely used due to their excellent characteristics such as low voltage actuation, thin model display, or the like. Examples of the display systems of conventional liquid crystal display elements, particularly small-to-medium-sized elements, include TN (twisted nematic), STN (super twisted nematic), active matrix based on TN (TFT: thin film transistor), and the like, and they utilize liquid crystal compositions having positive dielectric anisotropy values.
However, these display systems have a narrow viewing angle as one of their defects, and an improvement thereof has become a major issue in accordance with the currently increasing demand for larger liquid crystal panels. As a solution to this, display systems such as vertical alignment mode, IPS (In Plane Switching), and the like have recently been newly put to practical use. The vertical alignment mode is a system to improve the viewing angle by utilizing vertical alignment of liquid crystal molecules, in which a liquid crystal composition having a negative dielectric anisotropy value is used. IPS is a system to improve the viewing angle by switching liquid crystal molecules using a horizontal electric field in parallel with glass substrates, in which a liquid crystal composition having a positive or negative dielectric anisotropy value is used. Thus, the vertical alignment mode and IPS, which are display systems effective for improving the viewing angle, require liquid crystal compounds and liquid crystal compositions having negative dielectric anisotropy values, which have become strongly demanded. However, liquid crystal compounds or liquid crystal compositions having negative dielectric anisotropy values have not been sufficiently developed, because conventional display systems mainly use liquid crystal compositions having positive dielectric anisotropy values as described above.
As a liquid crystal compound having a negative dielectric anisotropy value, a liquid crystal compound having a 2,3-difluorophenylene skeleton (see Patent Document 1) and a liquid crystal compound having a 3,4-difluoro-5,6,7,8-tetrahydronaphthalene skeleton (see Patent Document 2) are disclosed. However, the absolute values of the dielectric anisotropy values of these compounds are not necessarily sufficiently large, which prevents the progress of the development of liquid crystal display elements, so a compound having a large absolute value of negative dielectric anisotropy value is required to be developed.
As a compound having a large absolute value of dielectric anisotropy, a liquid crystal compound having a 1,7,8-trifluoronaphthalene skeleton is disclosed (see Patent Document 3). However, although this compound has a large absolute value of the dielectric anisotropy, the refractive index anisotropy thereof is large because the compound has a naphthalene skeleton. Therefore, it is difficult to apply the compound to a liquid crystal composition having a small refractive index anisotropy.
On the other hand, application of a compound having a chroman ring to a liquid crystal material has already been known (see Patent Documents 4 and 5). However, the compounds described in these documents are intended to be used for ferroelectric liquid crystal compositions, because the compounds have an unsubstituted chromam ring as well as an optically-active group. Moreover, there is no disclosure with respect to negative dielectric anisotropy in these documents. Also, chroman-based compounds which are intended for conventional nematic liquid crystal compositions and in which an optically-active group is not essential are known (see Patent Document 6). However, the described compounds are compounds each having an unsubstituted chroman ring, and seem to be intended for ferroelectric liquid crystal compositions. Moreover, most of the compounds have positive dielectric anisotropy, and compounds having negative dielectric anisotropy are not disclosed.
As mentioned above, a liquid crystal material having a large absolute value of negative dielectric anisotropy and small refractive index anisotropy has been required to be developed.
(Patent Document 1) German Laid-Open Patent Application No. 3906019
(Patent Document 2) German Laid-Open Patent Application No. 19522145
(Patent Document 3) German Laid-Open Patent Application No. 19522195
(Patent Document 4) Japanese Laid-Open Patent Application No. Hei 5-25158
(Patent Document 5) Japanese Laid-Open Patent Application No. Hei 6-256337
(Patent Document 6) Japanese Laid-Open Patent Application No. Hei 6-256339

Chroman derivative and liquid-crystal composition containing the compound

Abstract: (wherein W1 and W2 each independently represents fluorine, chlorine, —CF3, —CF2H, —OCF3, or —OCF2H) and has negative dielectric anistropy.


Steps of a process for visualization of a detonation wave involve examini measuring, and confirming a fuel-air explosion by using a ground-based fuel bottle oriented horizontally whereby the explosive dissemination creates a fuel-air cloud with its diameter in the vertical plane and a timed delay, proximate charge explodes within the created cloud. A ground-based high speed camera with a line-of-sight, end-on position with respect to the bottle, photographically records the existence of any occurring detonation wave.

1. Field of Invention
The present invention relates to a process for visualization of a detonation wave which process photographically proves or confirms the existence of the detonation wave for a wide range of fuel-air mixtures.
2. Description of the Prior Art
The prior art of detecting detonation in a fuel-air mixture employs an arrangement of a ground-based canister of fuel and a high-speed camera mounted in a high tower, far above the ground. Further, the prior art of detecting detonation in a fuel-air mixture largely consists of using pressure gauges and high-speed cameras. If each of the gauges arranged in a row or a line discloses a peak pressure of 300 psi (more or less) in a detonating fuel-air mixture, it is accepted that a detonation wave has passed though the mixture. If processed high-speed film reveals a bright front of fire consuming the mixture at 5900 feet/second (more or less), it is accepted that a detonation wave has passed through the mixture. These two detection methods--especially the gauge method--are used in laboratory detonation tests. In a field test of fuel-air explosives (FAE's), it is common to use both methods in the same test. It is to be noted that detonation and explosion are separate and distinct operations in the FAE prior art.
Detonation is defined . . . as an exothermic reaction which propagates at supersonic velocity. Explosion is defined as a rapid exothermic reaction at subsonic velocities . . . it will be understood that detonation of a fuel-air cloud is always the desired goal, rather than explosion of such cloud which would be accompanied by overpressures of lesser magnitude. Detonation occurs only over an area in which the volume percent of fuel in air in the cloud is within certain fairly well defined upper and lower limits generally referred to as the detonability limits. Ordinarily a time delay of a few seconds is introduced between impact of the device and detonation of the cloud to allow for fuel dispersal time and for the cloud to grow in size over some desired area. Any factor which affects fuel dispersal or cloud growth may inhibit the development of the desired fuel-air ratio over this area . . . If the volume percent of fuel in such a cloud exceeds the upper detonability limit of the fuel, then no detonation will occur and the device is not completely successful even though the possibility of burning or explosion may still exist; (Column 1 of U.S. Pat. No. 3,955,509 to Carlson, issued May 11, 1976). This patent disclosure is incorporated herein by reference.
State of the art fuel-air explosive (FAE) weapons require two distinct events for a successful detonation. The first event is dispersal of a fuel into either a large gas cloud or a two phase cloud of very small fuel droplets and air. A gas cloud is formed from compressed gas, while a two phase cloud is formed from a liquid, such as propylene oxide. Either type fuel may be used, and in both cases, formation of the cloud relies upon a high-explosive central burster that not only ruptures the bomb case but also imparts a very high radial velocity to the fuel. The time required for cloud formation is a function of several factors, size of central burster, amount of fuel, type of fuel, configuration of central burster, and weapon configuration . . . Once the cloud has been formed, a detonation is initiated by introducing a minimum amount of energy into the cloud at nearly the instant it reaches the proper fuel-air ratio . . . The generally adopted method has been to use a high explosive charge. The size of the charge depends on the fuel-air ratio of the cloud and on the proximity of the charge to the cloud. The detonation of the explosive charge is considered the second event in a fuel-air explosion, and the system that deploys that charge is termed the second event system, or the cloud detonator system . . . A successful fuel-air explosion requires a rather precise system to initiate detonation of the cloud. The high explosive charge must be placed directly in the cloud if a minimum size charge is used, since the amount of explosive required to initiate the cloud increases quickly as the distance from the cloud increases. The timing of the detonation of the initiating charge is also critical because the time during which the cloud is detonable is a very short. (Column 1 of U.S. Pat. No. 3,999,482 to Bilek, issued Dec. 28, 1976). This patent disclosure is incorporated herein by reference.
The process of the present invention concerns novel steps involving an arrangement of a high-speed camera and an unconfined fuel-air mixture. In the field use, a FAE mixture is usually generated by explosively disseminating liquid fuel from a canister. The dissemination breaks the bulk liquid into droplets that are propelled into the cloud, which is not thick, but of a large diameter. A second, time-delayed explosion actually initiates the fuel-air explosion. Applicant's pending U.S. application Ser. No. 07/953,165 filed Sep. 29, 1992 relates to FAE canister apparatus; this application disclosure is incorporated herein by reference. Examples of liquid fuel in the prior art are disclosed in the above-mentioned U.S. Pat. Nos. 3,955,509 and 3,999,482; also in U.S. Pat. Nos. 4,157,928 and 4,132,169.
3. Advantages Over the Prior Art
The detection steps of the process of the present invention constitute an important distinction over the photographic arrangement of the prior art. The process is not associated with the prior art electronic means of detection. The process of the invention involves the steps of examining, measuring, and confirming a fuel-air-explosion by using an elevated fuel bottle oriented horizontally so that the explosive dissemination will create a fuel-air cloud with its diameter in the vertical plane. In practicing the present process with ground-based components, a high-speed camera with a line-of-sight, end-on positioned with respect to the fuel jug or canister, can film the detonation (or burn) as it happens.
A fuel jug set upright in a vertical position will operatively produce a substantially circular shaped cloud whose thickness will be several jug (canister) heights. When the cloud is viewed from the side with a ground mounted camera, the cloud appears to be substantially rectangular shaped. When the cloud is viewed with an overhead mounted camera a substantially circular shape is revealed. A typical FAE cloud is actually shaped like a pillbox. Accordingly, it is fair to state that FAE clouds present a different appearance depending on the geometry between the observer and fuel bottle.
The detonation detection and confirmation result of the process of the present invention is made possible by understanding how actual cloud shape, viewpoint, and light scattering from the cloud affect and detract from camera-based detection systems.
a. Advantages Over the Side-On View: When viewed through the side of the cloud, the detonation wave does not have a sharply discernible front. The reason is that the detonation wave originates at the explosive-initiation point, which is deep within the cloud. The light from the detonation is scattered by all the droplets between the wave front and the camera. The scattering makes the location of the wave very imprecise. Another problem with the side-on view is that non-detonating pockets in the (inhomogeneous) fuel-air mixture are not revealed. It should be noted that these problems with the side-on view are not present when the fuel in the fuel-air mixture is in a gaseous state, rather than a droplet state. These detonations can be effected in laboratory and field experiments using shock tubes with windows or large, clear plastic bags. It is in the two-phase (gas and liquid/air) detonations effected by fuel jugs, that the process of the present invention is definitely required.
b. Advantages over the Overhead View: When the cloud is viewed from overhead, the problems of the side-on view disappear. As a general rule, the detonation front can be easily located and the smooth or jerky movement of the detonation wave can be seen over the whole cloud, depending on the homogeneity. Some disadvantages of the overhead view are the requirements for the high capital investment for equipment and the complexity of the apparatus. A high, safe tower (or a sky-wire nexus of three towers) and special camera-aiming equipment are required. Thus, the use of an overhead camera is a prior art solution to the problem of obtaining a proper visualizing of the detonation wave.
The process of the present invention has the advantages of the overhead view type and none of its disadvantages. The useful result attained by the prior art is also obtained by the present process in a simpler and direct manner, that is, both the cloud and the detonation wave are photographed at ground level. Both the growth of the cloud and the speed of the detonation wave can be measured. With the process of the invention, much survey work on fuel-air explosions can be performed faster and with fewer operators. With the correct parameters known, improved research and testing can be conducted and repeated with the fuel bottle placed conventionally and slightly elevated, and with a line of pressure gauges installed.

Process for visualization of a detonation wave

The United States of America as represented by the Secretary of the Army


An easy-entry system (EE) for a vehicle seat (1) with a backrest (1.1) and a seat cushion (1.2), in arrangement with a fitting (2) for adjusting the inclination of the backrest (1.1) relative to the seat cushion (1.2) at least within a comfort range and optionally with an extended comfort function for positioning the backrest (1.1) beyond an easy-entry position into a loading floor position. The system includes, for initiating an easy-entry function, at least one actuating lever (4) which is coupled via at least one tension element (6) to an unlocking lever (8) for unlocking the inclination adjustment of the backrest (1.1). A translatory movement of the tension element (6) is transformed by means of a sliding element (7.2) of a transmission arrangement (7) into a rotatory movement of the unlocking lever (8) for opening the fitting (2).

In the prior art, various easy-entry systems are known which permit easier boarding into a second row of seats of a vehicle. The easy-entry system is actuable by way of an unlocking lever, which is normally arranged on a backrest of the vehicle seat, whereby the backrest of the vehicle seat pivots out of a boarding region. If the vehicle seat is arranged on rails, it is possible, when the unlocking lever is actuated, for the vehicle seat to additionally or alternatively be displaceable out of the boarding region in the direction of travel.
DE 10 2005 003 817 A1 describes a motor vehicle seat having a seat part and having a backrest which is lockable by way of an unlocking mechanism in an inclination detent adjustment mechanism, said backrest being pivotable about a pivot axis, which is fixed relative to the seat part, by way of an easy-entry operating lever into an easy-entry position, and by way of a comfort/cargo operating lever, which is fixed relative to the seat part, into a comfort or cargo position, and having an unlocking lever, said unlocking lever being actuable by the easy-entry operating lever and the comfort/cargo operating lever and being mounted so as to be pivotable about the pivot axis being fixed relative to the seat part and being operatively connected by way of an unlocking shaft, which runs coaxially with respect to the pivot axis, to an adjustable locking element of the inclination detent adjustment mechanism, which locking element is engageable with detent action with a locking element, which is fixed relative to the seat part, of the inclination detent adjustment mechanism, wherein the unlocking lever is operatively connected to a pivoting hoop which is actuable by way of the easy-entry operating lever and which is preloaded into a locking position of the inclination detent adjustment mechanism and which is mounted so as to be rotatable about a pivoting hoop axis which is fixed relative to the backrest.
DE 10 2006 015 138 A1 has disclosed a motor vehicle seat having a seat part and having a backrest which is adjustable in terms of inclination and which is pivotable, about a pivot spindle fixed relative to the seat part, from a usage position into a forwardly inclined or folded-forward position and which is connected lockably and unlockably to the seat part by way of a detent adjustment fitting arranged on the pivot spindle, wherein the detent adjustment fitting is lockable and unlockable by way of a loading cable coupled thereto, which Bowden cable is actuable by way of a Bowden cable lever, wherein the Bowden cable lever of the Bowden cable is arranged above the backrest pivot spindle on the backrest frame, and wherein the Bowden cable core is guided around a first diverting roller, mounted in floating fashion on the pivot spindle, and about a second diverting roller, which is arranged within the backrest frame so as to be fixed relative to the seat part, and said Bowden cable core is fastened, by way of its end averted from the Bowden cable lever, to the free end of a detent adjustment fitting unlocking lever, the other end of which is connected rotationally conjointly to the pivot spindle.

Easy-entry system and vehicle seat with an integrated easy-entry system


A tire having a form ratio under 0.80, a metallic radial carcass reinforcement, and a working crown reinforcement of two working plies formed of non-extensible reinforcement elements oriented at angles xcex1 and xcex1xe2x80x2, with axial widths in the ranges between 0.65So to 0.80So and 0.35So to 0.45So, So being the maximum axial width of the median line of the carcass reinforcement, and two half-plies of non-extensible metallic elements making an angle xcex2 with the circumferential direction, where xcex2 is less than angles xcex1, xcex1xe2x80x2 by at least 2xc2x0, and is opposite to angle xcex1 of the widest axially continuous working ply, the half-plies located on either side of the equatorial plane XXxe2x80x2 having axial widths between 0.22So and 0.35So, and axially inside edges separated from the equatorial plane XXxe2x80x2 by a distance equal to half the width of the narrower working ply less an amount of at least 0.05So.

The invention concerns a tire whose form ratio H/S is at most equal to 0.80, and more particularly a tire of the xe2x80x9cheavy-dutyxe2x80x9d or xe2x80x9ccivil engineeringxe2x80x9d type.
A tire of this kind, which is generally designed to support heavy loads, comprises a radial carcass ply and a crown reinforcement consisting of at least two working crown plies formed of non-extensible reinforcement elements, crossed over from one ply to the next and making with the circumferential direction angles which may be equal or unequal, but which generally range between 10xc2x0 and 45xc2x0.
When the axial width S of such tires is increased without increasing their equatorial and rim seat diameters, i.e. if the height H of the tire on its rim is kept the same, it is found that the contact area on horizontal flat ground changes shape considerably for H/S ratios smaller than 0.65, and this despite the use of a working crown reinforcement that resists the stresses applied to it.
The contact area becomes axially wider but shorter in the longitudinal direction of the tire. This shortening in the longitudinal direction involves an increasingly pronounced retraction in the equatorial zone, to the point when the front and back edges of the contact area may come together, and the said area is then divided into two areas symmetrical with respect to the longitudinal axis of the tread.
Notwithstanding the advantages of wide treads and H/S form ratios smaller than unity, especially in touring vehicles, the unusual shape of the contact area of a tire with form ratio smaller than 0.80 has many disadvantages in the case of tires for heavy vehicles, owing to irregularity in the axial direction of the radial deformations of the carcass reinforcement/working crown reinforcement combination under the action of the stresses due to the inflation pressure.
The said disadvantages are of many kinds, and concern both the durability of the reinforcement armature and the resistance of the tread and the tire to soil aggression (wear, degradation, puncture, impacts, etc.).
To remedy the shortening of the contact area in the longitudinal direction and the resulting lack of durability of the crown reinforcement, patent FR 2 419 185 recommends positioning between the carcass reinforcement and the radially innermost working crown ply, and in two distinct areas of the equatorial plane, two limiting blocks each of which consists of two superimposed plies of non-extensible cables, crossed over from one ply to the next and making opposite angles with the circumferential direction, the absolute value of the said angles being half of the smallest angle used in the working plies and differing by 0xc2x0. Though the solution recommended in the said patent also improves the endurance of the tire since the resistance to separation between the working plies at their edges is increased, while the plies of the limiting blocks are not subjected to the said separation, in contrast it results in excessive fretting which brings the risk that the cables of the working plies may undergo compression when the tire is flattened.
To improve the wear of tires with low H/S values as well as their resistance to crown ply separation, U.S. Pat. No. 4,934,429 claims in contrast to the above that metallic cables can be used, which are extensible and whose orientation relative to the circumferential direction may be zero, the said cables forming part of an additional armature consisting of at least one ply in two portions, one on either side of the equatorial plane, the extensibility of the said cables being chosen as a function of the extension modulus desired respectively for the reinforcement ply or plies and for the crown plies.
The presence of additional armatures of circumferential reinforcement elements or ones very slightly inclined relative to the circumferential direction does not seem to be the best solution to give axial uniformity of the rigidities of the crown reinforcement and at the same time the contact pressures with the ground and/or the slippage between the tread and the ground.
The present invention proposes a different solution for achieving the above uniformity, a solution relating to the constitution and structure of the working crown reinforcement.
The tire according to this invention has a form ratio H/S smaller than 0.80 and comprises a radial carcass reinforcement consisting of at least one ply of non-extensible metallic reinforcement elements. This is covered radially by a working crown reinforcement consisting of at least two working crown plies which are axially continuous and are formed of non-extensible metallic reinforcement elements parallel to one another within each ply and crossed over from one ply to the next, so as to make with the circumferential direction angles xcex1 and xcex1xe2x80x2 between 10xc2x0 and 45xc2x0. The tire is characterized in that the two working plies have axial widths respectively within the ranges 0.65SO to 0.80SO and 0.35SO to 0.45SO where SO is the maximum axial width of the median line of the carcass reinforcement. The working crown reinforcement is completed by the presence of two half-plies consisting of non-extensible metallic elements which, relative to the circumferential direction, make an angle xcex2 smaller than the lesser of the two angles xcex1 and xcex1xe2x80x2 by at least 2xc2x0, the direction of xcex2 being opposite to the direction of the angle xcex1 of the widest axially continuous working ply. The said half-plies are positioned on either side of the equatorial plane and have axial widths between 0.22SO and 0.35SO, such that their axially inteal edges are separated from the equatorial plane by a distance equal to half the width of the narrower working ply, less an amount at least equal to 0.05SO.
It is preferable for the two axially continuous plies formed of elements oriented at angles xcex1 and xcex1xe2x80x2 to be radially closest to the carcass reinforcement and, in this context, the less wide ply is preferably the one closest to the radially outer-most ply of the carcass reinforcement, the said less wide ply having reinforcement elements oriented at an angle said to be xe2x88x92xcex1xe2x80x2 or to the left.
It is advantageous to add, radially outside the working reinforcement defined above and comprising two axially continuous plies of reinforcement elements and two first half-plies, a further two half-plies of non-extensible metallic elements parallel to one another within each half-ply and crossed over with the elements of the two radially lower half-plies making an angle xcex3 with the circumferential direction, the angle xcex3 being on the one hand larger than the largest of the angles xcex1 and xcex1xe2x80x2 of the axially continuous plies and on the other hand also larger than the angle xcex2 of the reinforcing elements of the first two half-plies by at least 10xc2x0.
The axially inside ends of the said two half-plies of elements oriented with the said angle y are separated from the equatorial plane by a distance equal to half the width of the widest axially continuous working ply, less an amount at least equal to 0.05SO.
The axially outer edges of the said half-plies of elements oriented at angle xcex3 may be positioned axially outside the axially outer edges of the two half-plies oriented at angle xcex2, but it is preferable for them to be separated from the equatorial plane by a distance at most equal to the distance between the axially outer edges of the plies oriented at angle xcex2 from the said plane.
The characteristics of the invention will be better understood from the description below, which refers to the drawing illustrating examples of embodiments in a non-limiting way.

Tire with crown reinforcement including half-plies

Compagnie Generale des Etabliesements Michelln-Michelln and Cie


This invention relates of the problem, to create a butterfly valve neck without an emergence of a gap between the butterfly valve neck and the butterfly valve. This invention disposes the problem trough a parted butterfly valve neck, with between attached sealing, where the butterfly valve rest on in the closed location. This invention causes, to reduce considerable the leakage air quantity, by the absent of a gap, between the butterfly valve neck and the butterfly valve in the closed location. An inhibition of the butterfly valve in the parted butterfly valve is no more possible. By the inventive sealing of this invention, the motor can operate with a lower idling speed and a smaller emission. Further, an advantage of this invention is the regulation (adjustment) of the dimension of the parted butterfly valve and the sealing, where-by each of the rule curves by starting will achieved from the closed location.

The invention relates to a method for the production of a throttle valve port.
Throttle valve ports are known. They involve generally single-part housings which have an air duct in which a throttle valve is arranged on a throttle valve shaft and the throttle valve shaft is mounted rotatably. The throttle valve port contains gear parts and drive assemblies which are required for actuating the throttle valve. DE 40 27 269 A1 describes a throttle valve port having a throttle valve shaft which can be actuated by an electric motor and mechanically by means of an adjusting lever. The electric motor is a stepping motor arranged on the throttle valve shaft without the interconnection of a coupling. The adjusting lever in this case is connected to the throttle valve shaft by means of a coupling spring. DE 198 25 727 A1 describes a throttle valve port which has a throttle valve which is mounted rotatably in a throttle valve housing and can be adjusted by an actuator via transmission elements. The transmission elements are arranged on or close to an element carrier, the element carrier being fastened to the throttle valve housing. A general disadvantage of the production of throttle valve ports of this type is that the inner parts which are to be integrated in the single-part throttle valve housing, such as, for example, the electric motor, springs, gear wheel segments and throttle valve and throttle valve shaft, have to be introduced into the housing of the throttle valve port on one side in one direction of assembly and then have to be mounted. This manner of manufacturing is relatively complicated, since exact tolerances have to be maintained. A highly automated assembly of throttle valve ports is therefore very complicated and is associated with considerable investment costs.
EP 0 947 681 A2 and US 2002/0104510 A1 disclose methods for the production of a throttle valve port, in which, in a first step, a first housing half and a second housing half are produced with corresponding recesses for inner parts by means of a casting process, then, in a second step, the inner parts are positioned in the first housing half or in the second housing half and then the first housing half and the second housing half are connected to each other in a third step. The first housing half and the second housing half are connected to each other horizontally, and therefore have a connection which runs perpendicularly to the longitudinal direction of the air duct. They are manufactured, for example, by means of metal or plastic, the chosen casting process being, for example, injection molding/diecasting. The inner parts are to be understood as meaning all of those technical components which are arranged in the throttle valve port. These are, for example, the throttle valve, throttle valve shaft, motor, springs, stamped gratings, gear wheel segments, electric components and connectors. These inner parts are positioned in the first housing half or in the second housing half, it being possible for this to take place, for example, by placing or clamping them in. The first housing half can be connected to the second housing half, for example, by screwing or bonding. This enables the inner parts to be fixed at the same time. It has surprisingly been shown that the throttle valve port can thereby be produced relatively rapidly and simply, with a relatively complicated and laborious assembly because of relatively inaccessible openings being dispensed with. The method is very readily suitable for assembly manually or for automatic manufacturing.
EP 0 947 681 A2 describes a throttle valve port having two housing halves of plastic while the throttle valve port according to US 2002/104510 A1 consists completely of metal.
The object of the present invention is to avoid the disadvantages of throttle valve ports manufactured entirely of one material.
According to the invention, in the first step, the first housing half or the second housing half are produced from plastic and the respectively other housing half is produced from aluminum. It is advantageous in this case that the inner parts can be clamped in a relatively simple and easy manner into the housing half of plastic and the respectively other housing half of aluminum can be placed on as a cover. The plastics used are duroplasts or thermoplasts having an appropriate thermal stability.
A preferred refinement of the invention involves, in the second step, the inner parts being positioned only in the first housing half or only in the second housing half. This simplifies automated production, since a housing half which does not have any inner parts can simply be placed onto the complementary housing half as a cover.
According to a further preferred refinement of the invention, at least some of the inner parts are combined to form subunits before the second step. It is thus advantageously possible, for example, to manufacture the motor from individual parts and to firstly produce a motor unit which has dome-type sliding bearings. The use of dome-type sliding bearings can therefore be implemented in a relatively simple and advantageous manner, since the corresponding recesses can easily be arranged beforehand in the casting process during the production of the first housing half and the second housing half.
A further refinement of the invention involves a subunit being a combination of the throttle valve and the throttle valve shaft. In this case, it is advantageous that the connection between the throttle valve and the throttle valve shaft can already be brought about before the positioning in the first housing half or in the second housing half, which is not possible in the known methods because of having to keep to tolerances.
According to a further preferred refinement of the invention, provision is made, in the third step, for a seal to be arranged between the first housing half and the second housing half. The sealing materials used in this case are, for example, plastics which are thermally stable up to approx. 150° C.
According to a further preferred refinement of the invention, in the third step, the second housing half is positioned in the region of the air duct with an encircling collar engaging in the first housing half. The air duct is generally of circular design. The encircling collar is a projection which engages in the first housing half in the third step. As a result, the first housing half and the second housing half can be fixed to each other in a relatively simple, advantageous manner, thus facilitating the arrangement of the inner parts in the throttle valve port.
According to a further preferred refinement of the invention, in the first step, the first housing half is produced with a relatively large first recess and the second housing half is produced with a relatively small second recess by means of a casting process, the first recess and the second recess together forming the air duct, and, in the third step, an insert with an internal taper is arranged between the first housing half and the second housing half, the internal taper of which insert forms the continuous transition from the relatively large first recess to the relatively small second recess. The arrangement of the insert with the internal taper makes it particularly advantageously possible to reduce the cross section of the air duct as required. All that is necessary for this is to appropriately exchange the second housing half and to arrange the insert with the internal taper. In this case, it is particularly advantageous that throttle valve ports which are already present are able to be appropriately retrofitted.
FIG. 1 illustrates the first housing half 1 and the second housing half 2 of the throttle valve port. In the method for the production of the throttle valve port, the first housing half 1 and the second housing half 2 are produced with the corresponding recesses for inner parts 4 by means of a casting process, in a first step. In a second step, the inner parts 4 are positioned in the first housing half 1. This takes place in the direction of the arrow. In this case, it is as a rule advantageous to combine at least some of the inner parts 4 to form a subunit 5 before the second step. The first housing half 1 has a first recess 3a and the second housing half 2 has a second recess 3b which form the air duct. In a third step of the method for the production of the throttle valve port, the first housing half 1 and the second housing half 2 are connected to each other. This can take place, for example, by screwing or bonding.
FIG. 2 is a three-dimensional illustration of a subunit 5 which comprises a plurality of inner parts. It involves the electric motor which is arranged in the first housing half 1. The combining of inner parts to form a subunit 5 in each case permits the advantageous arrangement of dome-type sliding bearings 4′ which can be inserted in a relatively simple manner into the recesses of the first housing half 1 or the second housing half (not illustrated).
FIG. 3 illustrates the first housing half 1 and the second housing half 2 in the region of the air duct with the first recess 3a and the second recess 3b in cross section. In this case, the second housing half 2 has an encircling collar 2′. In the third step of the method for the production of the throttle valve port, the second housing half 2 is positioned in the region of the air duct with the encircling collar 2′ engaging in the first housing half 1. This improves the connection between the first housing half 1 and the second housing half 2 and at the same time improves the fixing of the inner parts (not illustrated).
FIG. 4 illustrates an alternative arrangement of the first housing half 1 and of the second housing half 2 in the region of the air duct, in cross section. In the first step of the method for the production of the throttle valve port, the first housing half 1 is produced with a relatively large first recess 3a and the second housing half 2 is produced with a relatively small second recess 3b by means of a casting process. The first recess 3a and the second recess 3b together form the air duct. In the third step of the method, an insert 6 with an internal taper is arranged between the first housing half 1 and the second housing half 2, the internal taper of which insert forms the continuous transition from the relatively large first recess 3a to the relatively small second recess 3b. It is advantageous here that the diameter of the air duct may also be retrospectively reduced retrospectively by the arrangement of another, second housing half 2 and the insert 6, which is desirable in some cases.

Method for the production of a throttle valve port


A radio communication system, a radio communication apparatus, a radio communication method, and a computer program allow networks to be operated without interference between contending networks. When plural piconets collide on the same frequency channel, a control station of one of the piconets temporarily sets a buffer super frame period to maintain a coexistent relationship between the piconets. When an apparatus other than a control station receives a beacon signal of the buffer super frame period, a shorter super frame period based on that super frame period is temporarily set to make fine adjustment of the next beacon signal transmission timing. An apparatus that has not received a beacon signal looks for a beacon signal of its own piconet for a redundant time so as to find a start timing of a new super frame period.

1. Field of the Invention
The present invention relates to a radio communication system for effecting communication among a plurality of radio stations, a radio communication apparatus and a radio control method, and a computer program. Particularly, the present invention relates to a radio communication system in which a network is configured under the control of a particular control station, a radio communication apparatus and a radio communication method, and a computer program.
More particularly, the present invention relates to a radio communication system in which a plurality of wireless networks coexist, a radio communication apparatus and a radio communication method for controlling a communication operation in each wireless network in a communication environment wherein a plurality of wireless networks contends, and a computer program and, particularly to, a radio communication system, a radio communication apparatus and a radio communication method, and a computer program that are run, obviating interference among contending networks.
2. Description of the Related Art
A plurality of computers may be connected to constitute a local area network (LAN) to share information, such as files and data, and peripheral equipment, such as a printer, and to effect information exchange, including transfer of electronic mail and data contents.
Hitherto, LANs have generally been formed using optical fibers, coaxial cables, twist pair cables or other types of cables. This automatically requires line laying construction work that involves complicated cable routing, making it difficult for achieving easy configuration of networks. Furthermore, after configuring a LAN, equipment movable distances are inconveniently limited by cable lengths of the equipment. As a solution to this shortcoming, attention has been focused on a wireless LAN as a system for releasing users from the LAN wiring based on a conventional cable connection method. The wireless LAN makes it possible to obviate the need for most cables in a working area, such as an office, allowing communication terminals, such as personal computers (PCs) to be moved relatively easily.
With the recent trend toward increasing speed and lowering prices of wireless LANs, the demand for wireless LANs is markedly increasing. In particular, the introduction of a personal area network (PAN) is recently being discussed in order to effect information communication by configuring a small-scale wireless network for a plurality of electronic equipment installed around users. For instance, different radio communication systems are specified by using frequency bands not requiring permits by supervisory authorities, such as a 2.4 GHz band or a 5 GHz band.
According to, for example, IEEE802.15.3, activities for standardizing high-speed radio personal area networks exceeding 20 Mbps are being developed. According to the section, standardization based on a PHY layer mainly using 2.4 GHz-band signals is being promoted.
In this type of wireless personal network, one radio communication apparatus acts as a control station known as a "coordinator." A personal area network is formed within 10 meters, centering around the coordinator. The coordinator transmits a beacon signal at a predetermined interval, and the beacon interval is defined as a transmission frame period. A time slot used by each radio communication apparatus is allocated for each transmission frame period.
For allocating time slots, a method known as, for example, "guaranteed time slot" (hereinafter referred to as "GTS") is used. This is a communication method whereby transmission bands are dynamically allocated while guaranteeing a predetermined transmission capacity at the same time.
For example, a contention access period (hereinafter referred to as "CAP") and a contention free period (hereinafter referred to as "CFP") are prepared for a MAC layer specified by IEEE802.15.3. To effect asynchronous communication, a CAP is used to exchange short data or command information. To effect stream communication, dynamic time slot allocation based on a GTS is carried out in a CFP so as to perform channel time reservation transmission.
The MAC layer standardized by IEEE802.15.3 is specified such that it conforms to the standard specifications of other PHY layers in addition to a PHY layer using 2.4 GHz band signals. Moreover, standardization efforts are being started to use other PHY layers in addition to PHY layers using 2.4 GHz band signals for the PHY layer standardized by IEEE802.15.3.
Also recently, wireless LAN systems to which a spread spectrum diffusion (SS) method has been applied are being put in practical use. Furthermore, an ultra-wide band (UWB) transmission method has been proposed for a PAN or similar applications.
According to direct spread (DS) method, which is a kind of the SS method, a transmitting end multiplies an information signal by a random coding sequence called a "pseudo noise" (PN) code so as to spread an occupied band and transmits it, whereas a receiving end multiplies the received spread information signal by a PN code so as to effect reverse diffusion, thereby reproducing the information signal.
In the UWB, an impulse signal sequence of an extremely short period of about a few hundred picoseconds is used to produce an information signal to transfer the signal sequence. The occupied band width is equivalent to a band of a GHz order such that the value obtained by dividing the occupied band width by its central frequency (e.g., 1 GHz to 10 GHz) is approximately 1. The occupied band is an ultra-wide band, as compared with a band width normally used for a wireless LAN that employs the "W-CDMA" or cdma2000 method, the SS method or the orthogonal frequency division multiplexing (OFDM) method.
In a recent communication environment wherein information equipment typically represented by PCs has been disseminated and a number of equipment exists in an office in a mixed fashion, all the equipment being connected through wireless networks, a case may be observed where a small working environment is crowded with two or more wireless networks and a plurality of wireless networks coexists in the same frequency band. The "same frequency band" in this case includes the UWB radio communication method in which data is diffused over an extremely broad frequency band to transfer the data.
Especially in the case of a UWB radio communication network, it is highly probable that neighbor radio communication networks contend, since data is diffused over an extremely broad band to transfer data.
Meanwhile, an impulse signal sequence used in a UWB radio communication system does not have any particular frequency carriers, making it difficult to effect carrier sensing. Hence, if the UWB radio communication system is applied to the PHY layer in IEEE802.15.3, therefore, the absence of any particular carrier signals makes it impossible to conduct access control by using the carrier sensing standardized in the foregoing section. Hence, there is no other alternative but to depend on access control based on time division multiplexing.
In case of a small-scale wireless network system, such as a PAN, the existence of each network or a base station is not necessarily secured. Hence, it is required to solve the problem of contention among networks and to accomplish dynamic allocation of bands or resources when a new network is added in the same space or a network is brought in from another place.
According to the specifications of the PHY layer utilizing 2.4 GHz-band signals standardized by IEEE802.15.3 described above, a plurality of other radio communication systems exist in the same frequency band; therefore, the possibility of coexistence with such systems must be considered. According to the standardized network construction, the use of neighbor piconets is conceivable, in which control stations (hereinafter referred to as "PNCs") of networks operate the piconets, avoiding interference with each other. More specifically, specifications have been prepared on an assumption that an additional piconet is formed in the same space while an existing control station is transmitting a beacon signal.
The method for operating neighbor piconets standardized in IEEE802.15.3 specifies the use of a pseudo-static GTS to achieve coexistence of its own piconet and an associated piconet.
Thus, according to a conventional method, to create neighbor piconets, a plurality of piconets can be operated on the same frequency by disposing their beacons in ranges that are apart from each other.
In a PAN, however, moving a piconet automatically involves creation of another neighbor piconet, making it impossible to avoid overlapping beacon positions between neighbor piconets.
Furthermore, if neighbor piconets happen to share the same transmission period and transmission timing of a beacon signal, then radio communication apparatuses or devices existing in the two piconets cannot detect beacons from a control station, utterly disabling the operation of the piconets. The control station of course does not receive any signals while it is transmitting a beacon signal, so that it cannot detect by itself that its own beacon signal is colliding with another beacon signal.
In addition, according to the specifications in IEEE802.15.3, a device that can no longer receive a beacon signal will not be capable of identifying a frame structure described in the beacon signal, so that it can no longer transmit its information. Thus, there is no means for a device other than the one acting as the control station to send information to the control station.
The method for operating neighbor piconets according to the specifications in IEEE802.15.3 uses a pseudo-static GTS; hence, the allocation of a GTS once set may be changed by a command issued by a control station of a parent piconet.

Radio communication system, radio communication apparatus, radio communication method, and computer program


The present invention relates to a method of synthesizing trioxymethylene from formaldehyde by the catalytic action of an acidic ionic liquid. In the method, formaldehyde solution with a concentration of 30˜80 wt % is used as reactant, and an ionic liquid is used as catalyst. The cation moiety of the catalyst is selected from either imidazoles cation or pyridines cation, and the anion moiety of the catalyst is selected from one of p-tolyl benzene sulfonate, trifluoromethyl sulfonate, and hydrogen sulfate. In the present invention, ionic liquid is used, for the first time, as a catalyst to synthesize trioxymethylene from formaldehyde. The catalyst can be circularly used for continuous sampling.

1. Field of the Invention
The present invention relates to a method of synthesizing trioxymethylene from formaldehyde by the catalytic action of an acidic ionic liquid.
2. Description of the Related Art
Paraformaldehyde products are widely used in a variety of industries such as car manufacture, machinery, electricity, electronics, instrument, agriculture, manufacture of building materials, light industry, etc., for their superior chemical stability, mechanical strength, and plasticity. Currently, two major methods are used to manufacture paraformaldehyde international-wide, the gaseous formaldehyde method and the trioxymethylene method. Copolymerization technique wherein trioxymethylene is used as polymerizing monomer accounts for 80% paraformaldehyde products all over the world, and therefore techniques for troxymethylene synthesis are essential to paraformaldehyde synthesis. In addition, trioxymethylene is not only useful in the manufacturing of paraformaldehyde resin, but also an important chemical material having a variety of uses such as in the preparation of anhydrous formaldehyde and pesticide, moulding material, bonding material, disinfectant agent, antibacterial agent, etc. Trioxymethylene can be applied to all reactions involving formaldehyde, and is especially useful in reactions employing anhydrous formaldehyde as a reactant.
Currently, sulfuric acid method is commonly used to synthesize trioxymethylene in the industry. However, defects such as high corrosivity of dilute sulfuric acid, high demands on devices used in the method, high cost, large amount of by-products, etc., exist. In 1978, Wells et. al (U.S. Pat. No. 4,110,298) employed polyethylene glycol monobutyl ether as dilutent and used two phase reaction catalyzed by sulfuric acid to produce trioxymethylene. However, the introduction of the third constituent also brought difficulties to the later isolation procedure. Acidic ion exchange resin was used and supported phosphoric acid and sulfuric acid were used as catalysts subsequently (DE-C-1 593 990 and AT-B 252 913, U.S. Pat. No. 5,962,702), however, relatively good result was achieved only with high concentration of formaldehyde and under increased pressure. In 1999, Kashihara et al. (U.S. Pat. No. 5,929,257) reported a constantly stable system of producing trioxymethylene from formalin, in which raw materials need to be pretreated. Yoshida (U.S. Pat. No. 4,381,397, U.S. Pat. No. 4,563,536, Emig (U.S. Pat. No. 5,508,448, U.S. Pat. No. 5,508,449) and Hoffmockel (U.S. Pat. No. 6,124,480) et al. reported respectively in 1983, 1986, 1996, and 2000 that heteropolyacid or supported heteropolyacid was used as catalyst to produce trioxymethylene. However, all these methods need a large amount of catalyst or have high requirement on reaction conditions. In China, GuanJian et al. reported, in Natural Gas Chemical Engineering (period 5, 2005), that supported PW12/ AC catalyst prepared by dipping active carbon as support in phosphotungstic acid was used to produce trioxymethylene, and the catalyst showed high activity with the relative content of trioxymethylene in gas phase of up to 30%. However, 70% of formaldehyde was used as raw material.
It has been reported that it is cost-effective to use protonic acids (such as sulfuric acid, p-tolyl sulfonic acid etc.) as catalyst to produce trioxymethylene. However, since the protonic acids are highly corrosive, difficult to separate, and cause contamination, zirconium needs to be used as corrosive resistant material on the equipments, which is impractical due to its high cost; when Lewis acid (such as zinc chloride, tantalum pentachloride, bismuth trichloride, titanium tetrachloride, tin tetrachloride etc.) or heteropolyacid or other solid acids are used as catalysts, problems arise such as need for large amount of catalyst, difficult to isolate, and high cost. Therefore, what is needed is a trioxymethylene synthesis system with high-efficiency and low corrosivity, which can achieve effective catalytic circulation, and lower costs of production and investment.

Method of synthesizing trioxymethylene from formaldehyde by the catalytic action of an ionic liquid

Lanzhou Institute of Chemical Physics Chinese Academy of Sciences


A method of mass spectrometry is disclosed comprising digitising at least one individual signal or transient, determining in relation to the digitized signal or transient an indication of overlap and/or coalescence of ion arrivals in the digitized signal or transient, or one or more ion arrival envelopes in the digitized signal or transient, and marking or flagging the digitized signal or transient as suffering from overlap or coalescence of ion arrivals based on the indication.

It is known to record or digitise individual signals or transients arising from ion arrivals at an ion detector or electron multiplier using an Analogue to Digital recorder or an Analogue to Digital Converter ("ADC"). Orthogonal acceleration Time of Flight mass spectrometers may digitise ion arrival signals or transients relating to many thousands of individual time of flight separations. The digitised signals or transients are summed to produce a final summed or composite time of flight mass spectrum. Each individual time of flight spectrum, signal or transient may be processed in real time before summing. In the simplest case this processing may be the application of an amplitude threshold to isolate signals arising from ion arrivals from background noise or baseline noise. The signal at an individual digitised sample (i.e. an individual Analogue to Digital Converter time bins) or within a time of flight spectrum which is above the threshold is recorded and all other samples or intensity values in Analogue to Digital Converter time bins are set to zero or to a baseline value. Such a method is disclosed, for example, in US 2011/0049353 (Micromass). Multiple time of flight spectra processed in this way may then be summed or averaged to generate a final summed spectrum with reduced noise.
It is also known to process individual signals or transients which have been digitised to reduce the ion arrival signals or transients into time and intensity pairs. Such a method is disclosed, for example, in U.S. Pat. No. 8,063,358 (Micromass). Individual signals or transients which are reduced to time and intensity pairs may then be summed with other time and intensity pairs relating to other time of flight spectra, signals or transients in order to produce a final summed, composite or average spectrum. This method substantially removes the profile or line width of the digitised signal from the final summed spectra thereby increasing the effective time of flight resolution. It also simplifies implementation of dual Analogue to Digital Converter approaches to extending dynamic range, such as U.S. Pat. No. 8,354,634 (Micromass), and allows simple up-sampling of output spectral data rates.
Other methods of reducing the contribution of the single ion pulse width are described in U.S. Pat. No. 6,870,156 (Rather).
In methods which involve reducing individual transients to time and intensity pairs, each ion arrival has an associated analogue peak width. If two or more ions arrive simultaneously then these analogue peak widths may partially overlap making it impossible for a simple Finite Impulse Response filter, peak maxima or related peak detection method to isolate the arrival time and intensity of the individual ions. In such a case a response related to the average ion arrival time and summed area may be recorded rather than two individual ion arrival times and intensities.
This coalescing of two or more ion arrivals within a transient into a single time intensity pair can cause artefacts in the final summed data. Furthermore, the analogue peak width from ions of different mass to charge ratio species may overlap significantly within a single transient. This will result in an inaccurate representation of the signal intensity and an inaccurate measurement of the ion arrival time for each mass to charge ratio species.
A method of de-convolving such overlapping signals is described in U.S. Pat. No. 8,735,808 (Micromass). However, this method can be computationally intensive.
GB-2457112 (Micromass) discloses methods and apparatus for detecting ions.
GB-2506714 (Micromass) discloses calibrating dual ADC acquisition systems.
GB-2439795 (Micromass) discloses obtaining mass spectra from a Time of Flight mass spectrometer.
WO 98/21742 (Rockwood) discloses a multi-anode time to digital converter.
EP-2447980 (Makarov) discloses a method of generating a mass spectrum having improved resolving power.
US 2005/0114042 (Pappin) discloses a method and apparatus for deconvoluting a convoluted spectrum.
US 2004/0083063 (McClure) discloses a method and apparatus for automated detection of peaks in spectroscopic data.
It is desired to provide an improved method of mass spectrometry and an improved mass spectrometer.


The present invention relates to inhibitors of post-proline cleaving enzymes, such as inhibitors of dipeptidyl peptidase IV, as well as pharmaceutical compositions thereof, and methods for using such inhibitors. In particular, the inhibitors of the present invention are improved over those in the prior art by selection of particular classes of sidechains in the P1 and/or P2 position of the inhibitor. The compounds of the present invention can have a better therapeutic index, owing in part to reduced toxicity and/or improved specificity for the targeted protease.

Proteases are enzymes that cleave proteins at single, specific peptide bonds. Proteases can be classified into four generic classes: serine, thiol or cysteinyl, acid or aspartyl, and metalloproteases (Cuypers et al., J. Biol. Chem. 257:7086 (1982)). Proteases are essential to a variety of biological activities, such as digestion, formation and dissolution of blood clots, reproduction and the immune reaction to foreign cells and organisms. Aberrant proteolysis is associated with a number of disease states in man and other mammals. In many instances, it is beneficial to disrupt the function of one or more proteolytic enzymes in the course of therapeutically treating an animal.
The binding site for a peptide substrate consists of a series of "specificity subsites" across the surface of the enzyme. The term "specificity subsite" refers to a pocket or other site on the enzyme capable of interacting with a portion of a substrate for the enzyme. In discussing the interactions of peptides with proteases, e.g., serine and cysteine proteinases and the like, the present application utilizes the nomenclature of Schechter and Berger [(1967) Biochem. Biophys. Res. Commun. 27:157–162)]. The individual amino acid residues of a substrate or inhibitor are designated P1, P2, etc. and the corresponding subsites of the enzyme are designated S1, S2, etc, starting with the carboxy terminal residue produced in the cleavage reaction. The scissile bond of the substrate is amide bond between S1–S1′ of the substrate. Thus, for the peptide Xaa1-Xaa2-Xaa3-Xaa4 which is cleaved between the Xaa3 and Xaa4 residues, the Xaa3 residue is referred to as the P1 residue and binds to the S1 subsite of the enzyme, Xaa2 is referred to as the P2 residue and binds to the S2 subsite, and so forth.
Dipeptidyl peptidase IV (DPIV), for example, is a serine protease which cleaves N-terminal dipeptides from a peptide chain containing, preferably, a proline residue in the penultimate position, e.g., in the P1 position. DPIV belongs to a group of cell-membrane-associated peptidases and, like the majority of cell-surface peptidases, is a type II integral membrane protein, being anchored to the plasma membrane by its signal sequence. DPIV is found in a variety of differentiated mammalian epithelia, endothelia and hemapoetic cells and tissues, including those of lymphoid origin where it is found specifically on the surface of CD4+ T cells. DPIV has been identified as the leukocyte differentiation marker CD26.

This patent is subject to a terminal disclaimer.

Peptidomimetic inhibitors of post-proline cleaving enzymes


A system and associated method for dynamically configuring a multiplatform computing environment are disclosed. At least one service may form a workflow to be executed as an ordered group. A database contains configuration data, workflow control data, and workflow status data. A service configuration utility provides user interface to dynamically receive configuration data, to update the database, and to display contents of the database. A workflow entry process creates a workflow. A service monitor controls runtime behaviors of the system according to contents of the database. A service listener routes a workflow to associated services according to the configuration data in the database. A service executes a desired function, and then reports a result to the system monitor. The system monitor updates contents of the database to reflect the reported result.

Conventional static configuration systems of applications in a multiplatform environment require complicated manipulation to change the contents of configuration. Also, events cannot be grouped based on a service that an event provides.
To change configuration in a conventional multiplatform computing environment, users of such system need support from a system administrator who is skilled and authorized to reconfigure the system. Thus, users cannot efficiently utilize the system as they need. In cases of database manipulation, any portion of database manipulation requiring changes of the contents of system configuration must be handled by a system administrator as well. Also, in a conventional system using static configuration, it is impossible to group related events and process a group of events by one service.
Consequently, there is a need for a system and associated method to overcome at least one of the preceding disadvantages of current static configuration systems in a multiplatform environment.

System and method for dynamically configuring a multiplatform computing environment

International Business Machines Corporation


A cart with one or more of a power supply system that includes an outlet box and a plurality of flexible receptacles, a bi-layer shelf, a positionable cable routing tray, and a removable cable management module.

There are many situations in which multiple electronic devices (e.g., notebook computers, netbook computers, tablet computers, and other handheld devices) are simultaneously used. Carts are useful for storing, charging, and updating a plurality of electronic devices. Typical carts are cabinets with shelves for the electronic devices to rest on. Generally, each electronic device must be individually connected to power and/or network cables, and such cables are routed within the cart to various outlets.