A polyhydroxyalkanoate having a monomer unit composition represented by General Formula (1):

1. Field of the Invention
The present invention relates to a novel polyhydroxyalkanoate (PHA), a method for production of such PHA and microorganisms for use in the same.
2. Related Background Art
Synthetic polymers derived from petroleum have been used as plastics etc. for a long time. Recently, the treatment of the used plastics has become one of serious social problems. These synthetic polymers have advantages of hard-to-decompose have been used in the place of metal or glass materials. On mass consumption and mass disposal, however, this feature of hard-to-decompose makes them accumulated in waste-disposal facilities, or when they are burned, it causes increased carbon dioxide exhaust, and harmful substances such as dioxin and endocrine-disruptors may be generated to cause environmental pollution. On the other hand, polyhydroxyalkanoates (PHAs) produced by microorganisms (hereinafter referred to as xe2x80x9cmicrobial polyesterxe2x80x9d) represented by poly-3-hydroxy butyric acid (PHB) can be used as the conventional plastics to make various kinds of products with melting processes etd., and can be decomposed by organisms unlike oil-derived synthetic polymers. Therefore, the microbial polyester is bio-decomposed and thus incorporated in the natural material cycle when discarded, and would not remain in the natural environment to cause pollution unlike many conventional synthetic polymer compounds. Furthermore, since the microbial polyesters do not require incineration processes, they are also effective in terms of prevention of air pollution and global warming. Thus, they can be used as a plastic enabling environmental integrity. In addition, the application of the microbial polyesters to medical soft members is under consideration (Japanese Patent Application Laid-Open No. 5-159, Japanese Patent Application Laid-Open No. 6-169980, Japanese Patent Application Laid-Open No. 6-169988, Japanese Patent Application Laid-Open No. 6-225921 and the like).
Heretofore, various bacteria have been reported to produce and accumulate PHB or copolymers of other hydroxyalkanoic acids in the cells (xe2x80x9cBiodegradable Plastics Handbookxe2x80x9d, edited by Biodegradable Plastics Society, issued by NTS Co. Ltd., P178-197, (1995)). It is known that such microbial PHAs may have a variety of compositions and structures depending on types of the producing microorganisms, the composition of culture media, culture conditions and the like, and up to now, studies regarding the control of these compositions and structures have been carried out to improve the properties of PHA.
For example, Alcaligenes eutropus H16 (ATCC No. 17699) and its mutant strains reportedly produce copolymers of 3-hydroxy butyric acid (3HB) and 3-hydroxy valeric acid (3HV) at a variety of composition ratios according to the carbon source in culture (Japanese Patent Publication No. 6-15604, Japanese Patent Publication No. 7-14352, Japanese Patent Publication No. 8-19227 and the like).
Japanese Patent Application Laid-Open No. 5-74492 discloses a method in which the copolymer of 3HB and 3HV is produced by bringing Methylobacterium sp., Paracoccus sp., Alcalugenes sp. or Pseudomonas sp. into contact primary alcohol having 3 to 7 carbons.
Japanese Patent Application Laid-Open No. 5-93049 and Japanese Patent Application Laid-Open No. 7-265065 disclose that two-component copolymers of 3HB and 3-hydroxy hexanoic acid (3HHx) are produced by culturing Aeromonas caviae using oleic acid or olive oil as a carbon source.
Japanese Patent Application Laid-Open No. 9-191893 discloses that Comamonas acidovorans IFO 13852 produces polyester having 3HB and 4-hydroxy butyric acid as monomer units in culture with gluconic acid and 1,4-butandiol as a carbon source.
Also, in recent years, active researches about PHA composed of 3-hydroxyalkanoate (3HA) of medium-chain-length (abbreviated to mcl) having up to about 12 carbons. Synthetic routes can be classified broadly into two types, and their specific examples will be shown in (1) and (2) below.
(1) Synthesis Using xcex2-Oxidation
Japanese Patent No. 2642937 discloses that PHA having monomer units of 3-hydroxyalkanoate having 6 to 12 carbons is produced by providing as a carbon source aliphatic hydrocarbon to Pseudomonas oleovorans ATCC 29347. Furthermore, it is reported in Appl. Environ. Microbiol, 58(2), 746 (1992) that Pseudomonas resinovorans produces polyester having 3-hydroxybutyric acid, 3-hydroxyhexanoic acid, 3-hydroxyoctanoic acid and 3-hydroxydecanoic acid at a ratio of 1:15:75:9 as monomer units, using octanoic acid as a single carbon source, and also produces polyester having 3-hydroxybutyric acid, 3-hydroxyhexanoic acid, 3-hydroxyoctanoic acid and 3-hydroxydecanoic acid (quantitative ratio of 8:62:23:7) as units, using hexanoic acid as a single carbon source. Herein, it is assumed that 3HA monomer units having longer chain length than that of the starting fatty acid are made by way of fatty acid synthetic route that will be described next in (2).
(2) Synthesis Using Fatty Acid Synthetic Route
It is reported in Int. J. Biol. Macromol., 16(3), 119 (1994) that Pseudomonas sp. 61-3 strain produces polyester made of 3-hydroxyalkanoic acids such as 3-hydroxybutyric acid, 3-hydroxyhexanoic acid, 3-hydroxyoctanoic acid, 3-hydroxydecanoic acid and 3-hydroxydodecanoic acid and 3-hydroxyalkenoic acids such as 3-hydroxy-5-cis-decenoic acid, 3-hydroxy-5-cis-dodecenoic acid, using sodium gluconate as a single carbon source.
By the way, the biosynthesis of PHA is usually carried out by a PHA synthase using as a substrate xe2x80x9cD-3-hydroxyacyl-CoAxe2x80x9d occurring as an intermediate of a variety of metabolic pathways in the cell.
Herein, xe2x80x9cCoAxe2x80x9d means a xe2x80x9ccoenzyme Axe2x80x9d. And, as described in the prior art of the above (1), the biosynthesis of PHA is carried out with xe2x80x9cD-3-hydroxyacyl-CoAxe2x80x9d occurring in the xe2x80x9cxcex2 oxidation cyclexe2x80x9d being a starting substance in the case where fatty acids such as octanoic acid and nonanoic acid are used as carbon sources.
Reactions through which PHA is synthesized by way of the xe2x80x9cxcex2 oxidation cyclexe2x80x9d will be shown below.
On the other hand, as described in the prior art of the above (2), in the case where the PHA is biosynthesized using saccharides such as glucose and the like, the biosynthesis is carried out with xe2x80x9cD-3-hydroxyacyl-CoAxe2x80x9d converted from xe2x80x9cD-3-hydroxyacyl-ACPxe2x80x9d occurring in the xe2x80x9cfatty acid synthesis pathwayxe2x80x9d being a starting substance.
Herein, xe2x80x9cACPxe2x80x9d means a xe2x80x9cacyl carrier proteinxe2x80x9d.
By the way, as described previously, the PHA synthesized in both (1) and (2) described above is PHA constituted by monomer units having alkyl groups in side chains. However, if a wider range of application of the microbial PHA like this, for example an application as a functional polymer is considered, it is expected that PHA having various substituents (for example phenyl groups) introduced in the side chain is significantly useful. With respect to the synthesis of such PHA, for the synthesis using xcex2 oxidation, a report regarding PHA having the aryl group and the like in the side chain can be found in, for example, Macromolecules, 24, p5256-5260 (1991). Specifically, it is reported that Pseudomonas oleovorans produces polyester having 3-hydroxy valeric acid, 3-hydroxyheptanoic acid, 3-hydroxynonanoic acid, 3-hydroxyundecanoic acid and 3-hydroxy-5-phenyl valeric acid (quantitative ratio of 0.6:16.0:41.1:1.7:40.6) as units in the amount of 160 mg for 1 L of culture solution (ratio in dry weight to the cell mass is 31.6%), using 5-phenylvaleric acid and nonanoic acid (mole ratio of 2:1, total concentration of 10 mmol/L) as a medium, and also produces polyester having 3-hydroxyhexanoic acid, 3-hydroxyoctanoic acid, 3-hydroxydecanoic acid and 3-hydroxy-5-phenyl valeric acid (quantitative ratio of 7.3:64.5:3.9:24.3) as units in the amount of 200 mg for 1 L of culture solution (ratio in dry weight to the cell mass is 39.2%), using 5-phenyl valeric acid and octanoic acid (mole ratio of 1:1, total concentration of 10 mmol/L). It is conceivable that the PHA in this report is principally synthesized by way of the xcex2 oxidation pathway due to that fact that nonanoic acid and octanoic acid are used.
As described above, in the microbial PHA, those with various kinds of compositions/structures are obtained by changing the type of microorganisms for use in its production, culture medium compositions, culture conditions, but if considering the application of the microbial PHA as plastics, they could not be sufficient yet in terms of properties. In order to further expand the range of the microbial PHA utility, it is important that the improvement of its properties are more widely considered, and for this purpose, the development and the search of the PHA containing monomer units of further diverse structures, its manufacturing processes and microorganisms enabling desired PHA to be produced efficiently are essential.
On the other hand, the PHA of a type having substituents introduced in the side chain as described previously is selected in accordance with the property for which the introduced substituent is desired, thereby making it possible to expect its development as a xe2x80x9cfunctional polymerxe2x80x9d having very useful functions and properties resulting from the property and the like of the introduced substituent, and the development and the search of excellent PHA allowing such functionality and the biodegradability to be compatible with each other, its manufacturing processes and microorganisms enabling desired PHA to be produced efficiently are also important challenges.
Another example of such PHA having substituents introduced in the side chain includes PHA having the above described phenyl groups, and further phenoxy groups in the side chain.
For another example of phenyl group, it is reported in Macromolecules, 29, 1762-1766 (1996) that Pseudomonas oleovorans produces PHA including 3-hydroxy-5-(4-toryl)valeric acid as a monomer unit through the culture in a culture medium including 5-(4-toryl)valeric acid (5-(4-methylphenyl)valeric acid) as a substrate.
Furthermore, it is reported in Macromolecules, 32, 2889-2895 (1999) that Pseudomonas oleovorans produces PHA including 3-hydroxy-5-(2,4-dinitrophenyl)valeric acid and 3-hydroxy-5-(4-nitrophenyl)valeric acid as monomer units through the culture in a culture medium including 5-(2,4-dinitrophenyl)valeric acid and nonanoic acid as a substrate.
Also, for an example of the phenoxy group, it is reported in Macromol. Chem. Phys., 195, 1665-1672 (1994) that Pseudomonas oleovorans produces PHA including 3-hydroxy-5-phenoxy valeric acid and 3-hydroxy-9-phenoxynonanoic acid as units from 11-phenoxyundecanoic acid.
Also, it is reported in Macromolecules, 29, 3432-3435 (1996) that Pseudomonas oleovorans is used to produce PHA including 3-hydroxy-4-phenoxybutyric acid and 3-hydroxy-6-phenoxyhexanoic acid as units from 6-phenoxyhexanoic acid, PHA including 3-hydroxy-4-phenoxybutyric acid, 3-hydroxy-6-phenoxyhexanoic acid and 3-hydroxy-8-phenoxyoctanoic acid as units from 8-phenoxyoctanoic acid, and PHA including 3-hydroxy-5-phenoxyvaleric acid and 3-hydroxy-7-phenoxyheptanoic acid as units from 11-phenoxyundecanoic acid. Excerpts of yields of polymers from this report are shown in Table 1.
Furthermore, in Can. J. Microbiol., 41, 32-43 (1995), PHA including 3-hydroxy-p-cyanophenoxyhexanoic acid or 3-hydroxy-p-nitrophenoxyhexanoic acid as a monomer unit is successfully produced with octanoic acid and p-cyanophenoxyhexanoic acid or p-nitrophenoxyhexanoic acid being a substrate, using Pseudomonas oleovorans ATCC 29347 and Pseudomonas putida KT 2442.
In Japanese Patent No. 2989175, a homopolymer constituted by 3-hydroxy-5-(monofluorophenoxy)pentanoate(3H5(MFP)P) units or 3-hydroxy-5-(difluorophenoxy)pentanoate(3H5(DFP)P) units and a copolymer containing at least 3H5(MFP)P units or 3H5(DFP)P units; Pseudomonas putida for synthesizing these polymers; and a method of producing the aforesaid polymers using Pseudomonas species are described.
These productions are carried out through xe2x80x9ctwo-stage culturexe2x80x9d as described below.
Time of culture: First stage, 24 hours ; Second stage, 96 hours
A substrate and a resulting polymer at each stage will be shown below.
(1) Resulting polymer: 3H5 (MFP) P homopolymer
Substrate at the first stage: Citric acid, Yeast extract
Substrate at the second stage: Monofluorophenoxyundecanoic acid
(2) Resulting polymer: 3H5 (DFP) P homopolymer
Substrate at the first stage: Citric acid, Yeast extract
Substrate at the second stage: Difluorophenoxyundecanoic acid
(3) Resulting polymer: 3H5 (MFP) P copolymer
Substrate at the first stage: Octanoic acid or Nonanoic acid, Yeast extract
Substrate at the second stage: Monofluorophenoxyundecanoic acid
(4) Resulting polymer: 3H5 (DFP) P copolymer
Substrate at the first stage: Octanoic acid or Nonanoic acid, Yeast extract
Substrate at the second stage: Difluorophenoxyundecanoic acid
As its effect, a medium-chain-length fatty acid having substituents may be materialized to synthesize a polymer having phenoxy groups with ends of the side chain replaced by one to two fluorine atoms, and stereoregularity and water repellency can be provided while maintaining a high melting point and good processability.
Also, PHA including cyclohexyl groups in monomer units is expected to show polymeric properties different from those of PHA including normal aliphatic hydroxyalkanoic acid as a unit, and an example of production using Pseudomonas oleovorans has been reported (Macromolecules, 30, 1611-1615 (1997)).
According to this report, when Pseudomonas oleovorans was cultured in a culture medium where nonanoic acid (hereinafter described as NA) and cyclohexylbutyric acid (hereinafter described as CHBA) or cyclohexyl valeric acid (hereinafter described as CHVA) coexisted, PHA including units containing cyclohexyl groups and units originating from nonanoic acid were obtained (each ratio unknown)
About the yields, it is reported that quantitative ratios of CHBA and NA are varied with substrate concentration total of 20 mmol/L and results as shown in Table 2 were obtained.
However, in this example, the yield of polymers per culture solution is not sufficient, and the obtained PHA itself has aliphatic hydroxyalkanoic acid coexist in its monomer unit.
In this way, in the case where PHA with a variety of substituents introduced in the side chain is produced, as seen in the reported example of Pseudomonas oleovorans described previously and the like, a method is used in which alkanoate having a substituent to be introduced is used not only as a stock for the polymer but also as a carbon source for growth.
However, for the method in which alkanoate having a substituent to be introduced is used not only as a stock for the polymer but also as a carbon source for growth, the supply of an energy source based on the production of the acetyl-CoA by xcex2 oxidation from such alkanoate is expected, and in this method, only a substrate having a certain degree of chain length is capable of producing acetyl-CoA by xcex2 oxidation, thus limiting alkanoate that can be used as a substrate of PHA, which is a major problem. Also, generally, since substrates with the chain length decreased by two methylene chains an after another are newly produced by the xcex2 oxidation, and these are captured as monomer units of PHA, the PHA that is synthesized is often a copolymer constituted by monomer units that are different in the chain length by two methylene chains one after another. In the reported example described above, a copolymer constituted by three types of monomer units, that is 3-hydroxy-8-phenoxyoctanoic acid originating from 8-phenoxyoctanoic acid which is a substrate, 3-hydroxy-6-phenoxyhexanoic acid and 3-hydroxy-4-phenoxybutyric acid which are by-products originating from metabolites is produced. In this respect, if PHA constituted by single monomer units is to be obtained, it is quite difficult to use this method. Furthermore, for a method premised on the supply of an energy source based on the production of acetyl-CoA by the xcex2 oxidation, the growth of microorganisms is slow and the synthesis of PHA requires lots of time, and the yield of the synthesized PHA is often low, which is also a major problem.
For this reason, a method in which, in addition to the alkanoate having substituents to be introduced, microorganisms are cultured in the culture medium in which fatty acids of medium-chain-length and the like such as octanoic acid and nonanoic acid as the carbon source for growth, followed by extracting PHA is considered to be effective and is generally used.
However, according to the study by the inventors, the PHA synthesized by way of the xcex2 oxidation pathway using fatty acids of medium-chain-length such as octanoic acid and nonanoic acid as the carbon source for growth has poor purity, and 50% or more of the polymers are made of mcl-3HA monomer units originating from the carbon source (for example, 3-hydroxyoctanoic acid, 3-hydroxynonanoic acid and the like). These mcl-3HA units make polymers adhesive at room temperature when they are sole components, and if they coexist in the PHA of the present invention in large quantity, the glass transition temperature (Tg) of the polymer is significantly lowered. Thus, to obtain hard polymers at room temperature, the coexistence of mcl-3HA monomer units is not desired. Also, it is known that such a hetero-side chain structure interferes intra-molecular or inter-molecular interaction originating from the side chain structure, and has significant influence on crystallinity and orientation. For achieving the improvement of polymer properties and the addition of functionality, the coexistence of these mcl-3HA monomer units raises a major problem. Means for solving this problem includes providing a refinement process to separate/remove xe2x80x9cundesiredxe2x80x9d monomer units such as mcl-3HA monomer units originating from the carbon source for growth, in order to acquire PHA constituted by monomer units having only specified substituents. However, the problem is that operations are complicated and a significant decrease in the yield can not be avoided. A more serious problem is that if desired monomer units and undesired monomer units form a copolymer, it is quite difficult to remove only undesired monomer units. Particularly, in the case where the purpose is to synthesize PHA including monomer units having groups obtained from unsaturated hydrocarbons, ester groups, aryl groups, cyan groups, nitro groups, groups obtained from halogenated hydrocarbons, groups having epoxide and the like introduced therein as side chain structures, the mcl-3HA monomer unit often forms a copolymer with a desired monomer unit, and it is extremely difficult to remove the mcl-3HA monomer unit after PHA is synthesized.
The present invention solves the above described problems, and provides PHA including monomer units of diverse structures having substituents in the side chain, which is useful as device materials, medical materials and the like, and a method of producing such PHA using microorganisms, and particularly a production method in which the coexistence of undesired monomer units is reduced, desired PHA can be obtained in high purity and also in high yields. The present invention is also intended to provide strains enabling such PHA to be synthesized in high purity and with efficiency.
According to one aspect of the present invention, there is provided a polyhydroxyalkanoate having a monomer unit composition represented by a general formula (1):
AmB(1xe2x88x92m)xe2x80x83xe2x80x83(1)
wherein A is represented by General Formula (2), B is at least one selected from the group consisting of monomer units represented by General Formula (3) or (4), and m has a value of 0.01 or larger and smaller than 1:
xe2x80x83wherein
n has a value of 0 to 10, k has a value of 3 or 5, and
R is at least one group selected from the group consisting of groups represented by General Formulae (5) to (7):
xe2x80x83in Formula (5)
R1 is a group selected from the group consisting of a hydrogen atom (H), halogen atoms, xe2x80x94CN, xe2x80x94NO2, xe2x80x94CF3, xe2x80x94C2F5 and xe2x80x94C3F7; and q is an integer selected from 1 to 8;
xe2x80x83in Formula (6)
R2 is a group selected from the group consisting of a hydrogen atom (H), halogen atoms, xe2x80x94CN, xe2x80x94NO2, xe2x80x94CF3, xe2x80x94C2F5 and xe2x80x94C3F7; and r is an integer selected from 1 to 8;
xe2x80x83in Formula (7)
R3 is a group selected from the group consisting of a hydrogen atom (H), halogen atoms, xe2x80x94CN, xe2x80x94NO2, xe2x80x94CF3, xe2x80x94C2F5 and xe2x80x94C3F7; and s is an integer selected from 1 to 8;
provided that following R are excluded from the choice:
when selecting one type of group as R in the general formula (2):
groups of Formula (5) in which R1 is H and q=2, R1 is H and q=3, and R1 is xe2x80x94NO2 and q=2;
groups of Formula (6) in which R2 is a halogen atom and r=2, provided that two components are selected as B from General Formula (3) or (4), R2 is xe2x80x94CN and r=3, and R2 is xe2x80x94NO2 and r=3; and the groups of Formula (7) in which R3 is H and s=1, and R3 is H and s=2; and
when selecting two types of groups as R in General Formula (2), the combinations of two types of groups of Formula (6) in which R2 is a halogen atom and r=2, and R2 is a halogen atom and r=4, provided that one component is selected as B from General Formula (3) or (4).
According to one aspect of the present invention, there is provided 5-(4-trifluoromethylphenyl)valeric acid of Formula (21).
According to another aspect of the present invention, there is provided a method of producing a polyhydroxyalkanoate, comprising a step of culturing a microorganism capable of synthesizing a polyhydroxyalkanoate of which monomer unit is represented by Formula (1) from an alkanoate in a medium containing the alkanoate:
AmB(1xe2x88x92m)xe2x80x83xe2x80x83(1)
wherein A is represented by General Formula (2), B is at least one selected from the group consisting of monomer units represented by General Formula (3) or (4), and m is 0.01 or larger and smaller than 1,
xe2x80x83wherein
n is an integer selected from 0 to 10, k is 3 or 5, and
R is at least one group selected from the group consisting of the groups represented by General Formulae (5) to (7):
xe2x80x83in Formula (5)
R1 is a group selected from the group consisting of a hydrogen atom (H), halogen atoms, xe2x80x94CN, xe2x80x94NO2, xe2x80x94CF3, xe2x80x94C2F5 and xe2x80x94C3F7; and q is an integer selected from 1 to 8;
xe2x80x83in Formula (6)
R2 is a group selected from the group consisting of a hydrogen atom (H), halogen atoms, xe2x80x94CN, xe2x80x94NO2, xe2x80x94CF3, xe2x80x94C2F5 and xe2x80x94C3F7; and r is an integer selected from 1 to 8;
xe2x80x83in Formula (7)
R3 is a group selected from the group consisting of a hydrogen atom (H), halogen atoms, xe2x80x94CN, xe2x80x94NO2, xe2x80x94CF3, xe2x80x94C2F5 and xe2x80x94C3F7; and s is an integer selected from 1 to 8;
provided that following R are excluded from the choice:
when selecting one type of group as R in General Formula (2):
groups of Formula (5) in which R1 is H and q=2,
R1 is H and q=3, and R1 is xe2x80x94NO2 and q=2; the groups of Formula (6) in which R2 is a halogen atom and r=2, R2 is xe2x80x94CN and r=3, and R2 is xe2x80x94NO2 and r=3; and
groups of Formula (7) in which R3 is H and s=1, and R3 is H and s=2; and
when selecting two types of groups as R in General Formula (2),
groups of Formula (6) in which R2 is a halogen atom and r=2.
According to a further aspect of the present invention, there is provided a process of producing polyhydroxyalkanoate, comprising a step of culturing a microorganism capable of producing the polyhydroxyalkanoate utilizing alkanoate in a medium containing the alkanoate and a saccharide.
According to a further aspect of the present invention, there is provided a process of producing polyhydroxyalkanoate, comprising a step of culturing a microorganism capable of producing a polyhydroxyalkanoate utilizing an alkanoate in a medium containing the alkanoate and a polypeptone.
According to a further aspect of the present invention, there is provided a process of producing polyhydroxyalkanoate comprising a step of culturing a microorganism capable of producing a polyhydroxyalkanoate utilizing an alkanoate in a medium containing the alkanoate and an organic acid participating in TCA cycle.
According to a further aspect of the present invention, there is provided a process of producing polyhydroxyalkanoate, wherein the a microorganism is cultured in at least two steps: one is in a medium containing an alkanoate and a polypeptone and the subsequent one is in a medium containing the alkanoate and pyruvic acid or salt thereof with nitrogen source limitation.
According to a further aspect of the present invention, there is provided Pseudomonas cichorii H45, FERM BP-7374.
According to a further aspect of the present invention, there is provided a novel bacterial strain Pseudomonas cichorii YN2, FERM BP-7375.
According to a further aspect of the present invention, there is provided a novel bacterial strain Pseudomonas putida P91, FERM BP-7373.
According to a further aspect of the present invention, there is provided a novel bacterial strain Pseudomonas jessenii P161, FERM BP-7376.
As already stated above, the present invention provides novel polyhydroxyalkanoates and novel substituted alkanoic acids to be a raw material therefor and novel microorganisms which have ability to produce and accumulate in the cell the novel polyhydroxyalkanoates, and provides methods for producing the polyhydroxyalkanoates using such microorganism. According to them, the polyhydroxyalkanoates useful as functional polymers in which different functional groups are introduced can be manufactured very efficiently and in high purity, therefore it may be expected to be applied to each field such as device and medical materials.

Polyhydroxyalkanoate, method for production thereof and microorganisms for use in the same

Abstract: xe2x80x83in Formula (5)

Abstract: xe2x80x83in Formula (6)

Abstract: xe2x80x83in Formula (7)

Abstract: R3 is a group selected from the group consisting of a hydrogen atom (H), halogen atoms, xe2x80x94CN, xe2x80x94NO2, xe2x80x94CF3, xe2x80x94C2F5 and xe2x80x94C3F7; and s is an integer selected from 1 to 8.

Abstract: The efficient production methods are also provided.


A liquid crystal composition including: a polymerizable liquid crystal compound capable of expressing birefringence with inverse wavelength dispersion; and a (meth)acrylate compound containing two or more (meth)acryloyl groups per one molecule, wherein: an amount of the (meth)acrylate compound is 8 parts by weight or less, the amount being relative to 100 parts by weight of a sum total of the polymerizable liquid crystal compound and the (meth)acrylate compound.

As a method for producing an optical film having a retardation with inverse wavelength dispersion, there is known a method using a polymerizable liquid crystal compound capable of expressing birefringence with inverse wavelength dispersion. In this method, a liquid crystal composition containing the aforementioned polymerizable liquid crystal compound is applied onto a suitable substrate such as a resin film to form a layer, the polymerizable liquid crystal compound is oriented in the layer of the liquid crystal composition, and the layer is cured while the orientation of the polymerizable liquid crystal compound is kept in a state of being maintained. A retardation with inverse wavelength dispersion is expressed in the liquid crystal cured layer obtained by curing the layer of the liquid crystal composition, whereby the aforementioned method can provide a desired optical film (see Patent Literature 1).

Liquid crystalline composition, liquid crystal cured layer, method for producing same, and optical film


A scanning probe microscope positioner including an elongated rigid member which is controllably tilted in a predictable manner. One end of the rigid member is subjected to differential motion on opposite sides of its longitudinal axis so as to cause its opposite end to partake of lateral displacement which is a magnification of the differential motion. By a careful selection of component materials and sizes, inherent thermal compensation can be attained.

This invention relates to a small motion transducer positioner for use in a micropositioning device to control the position of a probe tip relative to the surface of a sample under observation and, more particularly, to an improved positioner for eliminating Abba offset error even though tilting of the positioner is effected.
Segmented piezoceramic tubes are commonly used as actuators to produce probe tip motion in micropositioning devices such as scanning probe microscopes and profilometers. Such actuators have the advantages of simplicity, long range, small size and stiffness. What is disadvantageous about these actuators is the unpredictable tilting of the end of the tube, which introduces motion that is difficult to measure. This problem, known in the field of dimensional metrology as Abba offset error, is described, for example, in the article "Dimensional Metrology with Scanning Probe Microscopes" J. Appl. Phys., Volume 74, No. 9, Nov. 1, 1993, pages 83-109. U.S. Pat. No. 5,306,919, issued Apr. 26, 1994, to Elings et al proposes a solution to the problem of unwanted tilting by bending a piezoelectric tube into an S shape. This proposed solution is not entirely satisfactory because the bending leads to unpredictable tilting. It is therefore a primary object of the present invention to provide a positioner for a micropositioning device which eliminates unpredictable tilting so that Abba offset error is eliminated.
It would also be desirable to provide such a positioner which magnifies actuator movement to achieve long range, is thermally compensated, can be used for two and three dimensional motion, and is of simple construction. It is therefore another object of the present invention to provide a positioner possessing all of these attributes.

Tilting positioner for a micropositioning device


A system for reading an image formed on a silver-salt film, comprising: (a) a magnetic information reading unit for reading magnetic information recorded on a magnetic recording medium on the film; (b) a feeding unit for feeding the film; (c) an illuminating unit for irradiating light to the image formed on the film; (d) a filter unit arranged between the illuminating unit and the film; (e) a photoelectric conversion unit for receiving the light from the illuminating unit, which is passed through the film, to convert the image formed on the silver-salt film to an electric signal; (f) a memory unit for storing an image signal from the photoelectric conversion unit; and (g) a control unit for controlling at least one of the feeding unit, the illuminating unit and the photoelectric conversion unit, on the basis of information of the information reading unit.

1. Field of the Invention
The present invention relates to scanner systems and, more particularly, to a scanner system which converts image information of a film to electronic image information.
2. Related Art And Prior Art Statement
Conventionally, in Japanese Patent Publication No. SHO 56-7631 and Japanese Utility Model Publication No. SHO 63-36768, technical means is disclosed which reads a film by a one-dimensional sensor to convert the film to a video signal. Further, in recent years, proposed have been a film-image fetching apparatus such as a FOTOVIX (trade name: manufactured by Kabushiki Kaisha Tamuron) or the like, and a system for fetching image information of the film by an image pickup element such as a two-dimensional CCD or the like due to a macro mode or the like such as still video or the like.
Moreover, in Japanese Patent Laid-Open No. HEI 2-20170, technical means is disclosed which pre-scans a reading image to set a reading condition.
Meanwhile, U.S. Pat. No. 4,965,626 discloses a film capable of recording various information (date, correcting values, type or kind and the like) upon photographing.
Nevertheless, in the technical means due to Japanese Patent Publication No. SHO 56-7631, Japanese Utility Model Publication No. SHO 63-36768 and the like, in a case where an image of the film is electronically imaged, it is necessary to perform setting of brightness, setting of trimming, and the like by a hand or manual operation. Particularly, in a case where correction such as exposure correction or the like is performed upon film photographing, it is difficult for general users to conform to the condition. Furthermore, for the technical means which uses the above-described two-dimensional CCD, it is necessary to use a large-size two-dimensional sensor in order to improve resolution. This causes an increase in camera size and an increase in cost.
Further, in the technical means due to the above-described Japanese Patent Laid-Open No. HEI 2-20170, in a case where pre-scanning is performed to set various kinds of conditions, surplus or extra operation is required. Moreover, in a case where exposure correction is performed, or the like, advantages of the exposure correction cannot be expected.
Meanwhile, in a case where the image information of the film due to the aforesaid U.S. Pat. No. 4,965,626 is read by the scanner or the like, various information recorded as above mentioned cannot be fed-back. Thus, U.S. Pat. No. 4,965,626 has a problem that an adequate electronic image cannot be reproduced or cannot reappear.


A mix suitable for room temperature application which, on baking, forms a liquid-tight, electrically conductive seam between adjacent carbon blocks in an electrolytic cell for producing aluminum. The seam mix comprises carbon aggregate calcined to contain less than about 1.5% volatile matter, coal tar pitch or petroleum pitch binder, and an aromatic hydrocarbon solvent. A preferred composition of the seam mix has been found to exhibit less than two percent shrinkage upon heating to 950.degree. C.

The present invention relates to an improved mix of carbon aggregate and binder. More particularly, it relates to a seam mix applicable at room temperature for forming fluid-tight, electrically conductive seams between carbon blocks in the bottom of a Hall-Heroult cell for producing aluminum metal by the electrolysis of Al.sub.2 O.sub.3.
Background material on the technique of using seam mixes in the construction of Hall-Heroult cells is given in U.S. Pat. No. 2,378,142, issued June 12, 1945, to Hurter for a "Method for Making Furnaces for the Electrolytic Production of Aluminum" and in U.S. Pat. No. 3,576,700, issued Apr. 27, 1971, to M. B. Dell for "High Strength Joined Porous Block Structure and Method of Making Same". The seams are referred to in the Hurter patent as "interspaces".
According to the present method of seam mix usage in the construction of Hall-Heroult cells, prebaked cathode blocks of carbon are arranged in a cell bottom, separated by seams one to three inches wide. To obtain optimum properties, e.g. high density in the seam, conventional practice has been to preheat the carbon blocks to 60.degree. to 130.degree. C. with hot, for example, 130.degree. C., seam mix then being incrementally tamped into the seams and between the cell side lining and the blocks to provide a smooth cell bottom.
This practice is disadvantageous for a number of reasons. Fumes are evolved from the heated mix. Considerable manpower and coordination are needed to achieve the placement of the hot seam mix between the heated blocks before the mix has had a chance to cool. The elevated temperatures mean discomfort for the people performing the work. In addition, significant capital and operating costs are associated with the preheating of both the blocks and the seam mix.
A composition used for making molded carbon bodies but which has no utility as a room temperature seam mix is described in Greaves et al U.S. Pat. No. 2,637,072. The Greaves composition includes coal not subjected to calcining and containing 10-15% volatile matter, thereby resulting in excessive shrinkage upon heating to 950.degree. C. (see Example III below). A preferred formula for the Greaves carbon bodies contains coal tar pitch having a softening point of 105.degree. C. and is molded at a temperature of 100.degree. C., rather than at room temperature.


A multi-purpose table including a channel that either forms a portion of, or is attached to, a horizontal support structure of the work surface of the table. The channel includes at least one trough for managing cables and cords associated with electrical and communication outlet modules. The electrical and communication outlet modules may be installed within the channel with the outlets accessible to a user of the table when the work surface is positioned in each of a horizontal use position and a vertical storage position. In one embodiment, individual outlet modules are installed within the channel by a snap-fit engagement. In another embodiment, the outlet modules are provided as part of a harness or bus assembly that is slidably installed and retained within the channel.

1. Field of the Invention
The present invention relates to a multi-purpose table and, in particular, the present invention relates to a multi-purpose table having a channel for managing electrical and communication cables and outlets.
2. Description of the Related Art
Articles of office furniture, such as tables, are often used in environments which require electrical outlets and/or communication outlets near a work surface, such that a user may plug an electrical cord into the electrical outlet to power a device positioned on or proximate the article of furniture, or may plug a communication cable into the communication outlet to provide service to a device positioned on or proximate the article of furniture. Some municipalities allow articles of furniture to include electrical outlets having power supplied thereto via extension cords that are plugged into existing power outlets in a building or other structure in which the article of furniture is positioned. Other municipalities do not permit such extension cords and instead require that power that is supplied to the electrical outlets of the article of furniture are "hard wired" or fully contained within the article of furniture and are not connected to existing power outlets via extension cords.
Also, articles of furniture such as tables may be movable, particularly when same are used in a training or educational setting, in which the tables are often moved between use and storage locations and/or are reconfigured in different positions based on the dynamic needs of the environment. When it is necessary to supply power to peripheral devices used with the tables, such as computers and projectors, electrical and data cord management may present a challenge.
What is needed is an article of furniture having electrical and/or data supply and cord management features that is an improvement over the foregoing.

Multi-purpose table with electrical features


In a method and system for effecting bi-directional IR data communication between an object transceiver and a reader, the object transceiver transmits successive data packets to the reader, and upon termination of a transmission of each data packet, opens a time window for receiving a transmission from the reader. The object transceiver is typically one of a plurality of object transceivers each worn by a person to whom a short message is to be transmitted and each having a respective unique ID and being able to effect autonomous transmission to the reader. In such case, each object transceiver transmits for a negligible fraction of its duty cycle thereby reducing a likelihood that two or more object transceivers will try to transmit simultaneously. Alternatively, the same objective can be realized by controlling each object transceiver to have a randomly variable duty cycle.

This invention relates to a method and system for sending messages using low consumption portable tags that may be affixed to moving personnel or objects.
There are many situations in which it is required to alert or send messages to moving personnel. For example, in an office or hospital environment wherein members of staff move from one room to another, it is frequently necessary to send short messages to a staff member advising him or her, for example, of an incoming telephone message or an imminent appointment. One way in which this can be done is for each staff member to wear a portable tag which contains a memory for storing a unique identity which may be read by a respective interrogation device or reader located somewhere in each room. The tag may be provided with a buzzer for alerting the wearer of an incoming message shown on a display device in the tag. The portable tag transmits its ID at regular intervals to the reader so as to allow determination thereby of which portable tags are located in its vicinity. Whenever the person bearing the tag moves into a new room, his or her identity is automatically determined for onward transmission to a central tracking computer, which keeps a record of each person""s ID and his or her corresponding location.
The requirement that each portable tag must constantly transmit its ID to the interrogation device is undesirable because, by their very nature, the portable tags are miniature devices that are energized by a small internal power source such as a battery. The more data which is transmitted by each portable tag, the greater is the energy consumption and the more often the battery must be replaced.
Yet a further consideration must be borne in mind when data is transmitted using optical transceivers. For example, infrared (IR) transceivers are particularly suited for the kind of task in question and require an optically transparent path unencumbered by obstacles for effective data transmission. On the other hand, if even inadvertently optical transparency is maintained between one room and an adjacent room, then there exists the risk that a portable tag located in one room might transmit its ID to the interrogation device associated with a different, adjacent room. Such optical transparency might, for example, be the result of a dividing door between the two rooms being ajar; or owing to a window between the two rooms permitting infrared transmission therethrough.
Our co-pending Israeli Patent Application No. 126799 filed on Oct. 29, 1998 is directed to such a system which permits more than one portable tag to communicate with the interrogation device simultaneously. This desideratum clashes with the requirement to avoid collisions which, with IR transceivers is particularly onerous on account of the fact that it is difficult to detect collisions owing to the half-duplex communications protocol inherent in IR transmission. Such a requirement is met by assigning time slots for each of the IR transceivers and using polling techniques, thus allowing the interrogation device to address a portable tag at will by including the portable tag""s ID in the data stream transmitted thereby.
Such a system is thus highly versatile but at the cost of requiring a sophisticated data communications protocol. Furthermore, since a portable tag can be addressed at will, it must always be ready to receive data transmitted thereto by the interrogator. This requirement can be met by making the portable tag constantly active. However, bearing in mind that the portable tag is battery powered, this imposes an unacceptable burden on the battery. Alternatively, battery power may be conserved if the portable tag is normally dormant. However, in this case the portable tag must be xe2x80x9cawakenedxe2x80x9d by the interrogator before data can be received by the portable tag. This places yet a further overhead on the circuitry in the portable tag""s receiver, thereby increasing its cost.
When short messages are required to be transmitted to the tag in order to alert the bearer thereof to take certain action, for example, the quantity of data that needs to be transmitted to the portable tag is minimal. It is then possible to dispense with the requirement for independent free addressing of the portable tag. In such cases, the overhead associated with the sophisticated data communications in the system described in Israeli Patent Application No. 126799 may not be warranted.
It is thus an object of the present invention to provide a method for keeping track of objects in which the drawbacks described above are significantly reduced or eliminated.
It is a particular object of the present invention to provide an improved communications protocol suitable for use with IR transceivers allowing near simultaneous two-way communication between an interrogation device and a plurality of IR transceivers.
In accordance with a broad aspect of the invention there is provided a method for effecting bi-directional IR data communication between an object transceiver and a reader, the method comprising the following steps carried out by the object transceiver:
(One) transmitting successive data packets to the reader,
(Two) upon termination of a transmission of each of said data packets, opening a time window for receiving a transmission from the reader.
In accordance with a further aspect of the invention there is provided an object transceiver adapted for bi-directional IR data communication with a reader, the object transceiver comprising:
a transmitter for transmitting successive data packets to the reader, and
a timer responsive to termination of a transmission of each of said data packets, for opening a time window for receiving a transmission from the reader.
The invention also encompasses a reader for sending a message using IR data communication to a portable object transceiver, said reader comprising:
a receiver for receiving a transmission of a data packet from the portable object transceiver, and
a transmitter for sending the message to the portable object transceiver during a narrow time window opened thereby.
Furthermore, the invention encompasses a system comprising a server connected to a plurality of readers for sending a message using IR data communication to a portable object transceiver, wherein the server is adapted to:
(One) locate a respective one of said readers in communication with the portable object transceiver, and
(Two) send the message from the server to the respective reader for onward transmission to the portable object transceiver during a narrow time window opened thereby.
The object transceiver may be a portable battery-powered badge worn by movable personnel to whom short messages are to be communicated. In order to reduce the risk of data collision between different badges, each badge transmits for only 2 ms, successive data being transmitted after 60 seconds if the badge is stationary. In such case, the likelihood of two badges attempting to transmit during the identical 2 ms period is clearly negligible. When the badges move, the time interval between successive transmissions is randomly varied between 3 and 5 seconds. Thus, here too, the risk of two or more badges attempting to transmit within the same time slot may be sufficiently reduced. Obviously, conventional data collision techniques requiring re-allocation of time slots and re-transmission of data may be employed in the event that, notwithstanding efforts to the contrary, two different badge IDs are transmitted simultaneously.

Method and system for transmitting short messages to a portable IR transceiver


A pixel circuit of an organic electroluminescent display device and a method of driving the same. In the pixel circuit, a capacitor has a first electrode connected to a gate of a driving transistor, and a second electrode connected to a drain of a switching transistor. Further, a compensation voltage applying transistor is connected to the second electrode of the capacitor. The compensation voltage applying transistor compensates for a difference in IR-drops of a power supply voltage in response to a previous emission control signal. Further, the compensation voltage applying transistor cuts off the compensation voltage in an initialization period, thereby preventing a source of a data voltage and a source of the compensation voltage from being shorted with each other. Additionally, a threshold voltage compensation transistor is connected between the gate and the drain of the driving transistor. Therefore, a difference in threshold voltages of driving transistors is compensated.

1. Field of the Invention
The present invention relates to an organic electroluminescent display device, and more particularly, to a pixel circuit of an organic electroluminescent display device and a method of driving the same.
2. Description of the Related Art
An organic electroluminescent display device (or organic light emitting diode display device) is a flat panel display device that electrically excites an organic material (e.g., phosphorous organic compounds) to emit light. In an active matrix organic electroluminescent display device, a capacitor stores a voltage for representing a predetermined gray level, and the stored voltage is applied to a pixel for the entire duration of a frame. Based on the type of signal applied for storing the voltage in the capacitor, the active matrix organic electroluminescent display device can be classified into an active matrix organic electroluminescent display device using a voltage programming method or an active matrix organic electroluminescent display device using a current programming method.
Unlike a liquid crystal display (LCD) using voltage driven liquid crystal, the organic electroluminescent display device using the current programming method employs a current driven organic light emitting diode (OLED: also referred to as "an organic EL diode"). Therefore, the organic electroluminescent display device emits light at a luminance controlled by a driving current. Further, the organic electroluminescent display device includes a pixel circuit to generate the driving current.
FIG. 1 is a circuit diagram of a pixel circuit of a conventional organic electroluminescent display device, and FIG. 2 is a timing diagram for driving the pixel circuit of FIG. 1.
Referring to FIG. 1, the conventional pixel circuit includes first, second, third, and fourth transistors M1, M2, M3 and M4, first and second capacitors C1 and C2, and an organic EL diode OLED.
The first transistor M1 controls a current flowing to a drain thereof according to a voltage applied between a gate and a source thereof. The second transistor M2 applies a data voltage to the first capacitor C1 in response to a selection signal supplied from a scan line Sn.
The third transistor M3 connects the first transistor M1 to function as a diode in response to a selection signal supplied from a scan line AZn. The fourth transistor M4 transmits a driving current from the first transistor M1 to the organic EL diode OLED in response to a selection signal from a scan line AZBn.
The first capacitor C1 is connected between the gate of the first transistor M1 and a drain of the second transistor M2, and a second capacitor C2 is connected between the gate and the source of the first transistor M1.
Hereinafter, an operation of the conventional pixel circuit of FIG. 1 will be described in more detail with reference to FIG. 2.
First, when the third transistor M3 is turned on by the selection signal from the scan line AZn, the first transistor M1 is diode-connected, so that a voltage VDD−|Vth| is at a node N at which the first capacitor C1 and the second capacitor C2 are connected.
Then, when the third transistor M3 is turned off and a data voltage Vdata is applied, the voltage at the node N changes by as much as a variation ΔV=VDD−Vdata in the data voltage applied in the first capacitor C1. Therefore, the voltage at the node N changes into VDD−|Vth|−ΔV.
Then, when the selection signal from the scan line AZBn is applied, the fourth transistor M4 is turned on so that a driving current flows to the organic EL diode OLED.
The driving current IOLED flowing to the organic EL diode OLED can be obtained by the following Equation 1:IOLED=k(Vgs−|Vth|)2=k(VDD−VDD+|Vth|+VDD−Vdata−|Vth|)2=k(VDD−Vdata)2  [Equation 1]Here, VDD is a power supply voltage, Vth is a threshold voltage of the first transistor M1, and Vdata is the data voltage.
As shown in Equation 1, the above described conventional pixel circuit includes the first and second capacitors C1 and C2, and the third and fourth transistors M3 and M4, to compensate for a difference in threshold voltages of first transistors M1.
However, because the conventional pixel circuit needs three different scan lines Sn, AZn, and AZBn, the pixel circuit and the driving circuit are complicated and an aperture ratio of a light emitting display device including the pixel circuit is low.
Further, while one pixel is selected, the data is programmed in the conventional pixel after the difference in the threshold voltage is compensated for. Thus, a charging problem (or delay) makes it difficult to apply the conventional pixel circuit to a high-resolution panel.
Further, in the conventional pixel circuit, the driving current IOLED is controlled by adjusting the power supply voltage VDD and the data voltage Vdata, but a pixel close to the power supply voltage VDD and a pixel far from the power supply voltage VDD have different voltage drops (IR-drops) of the power supply voltage VDD. Therefore, even though substantially the same data voltage Vdata may be applied to the pixels, the luminance may still be non-uniform.
Also, the power supply voltage VDD for driving the conventional pixel circuit should be smaller than or equal to a maximum gray level voltage of the data voltage Vdata. In general, the data voltage Vdata has the maximum gray level voltage (or a black data voltage) of about 5V, so that the power supply voltage VDD should not be higher than 5V. Therefore, a reference voltage VSS needs to have a negative voltage (about −6V) to maintain a voltage difference of 11V between the power supply voltage VDD and the reference voltage VSS. This voltage difference reduces the efficiency of a DC-DC converter supplying the power supply voltage VDD and the reference voltage VSS.
As such, it may be desirable to design a new pixel circuit to address the foregoing problems.

Pixel circuit of organic electroluminescent display device and method of driving the same


An apparatus for processing glass sheets includes a furnace and a bending station traversed by a conveyor for carrying the glass sheets. A plurality of heaters mounted in the furnace each heat associated areas of the glass sheets in accordance with setpoint temperature signals representing desired values of temperatures for heating associated areas of the glass sheets. One or more parameters of the glass sheets, such as thickness and color, are sensed and the setpoint signal values are changed accordingly. The parameter values are also utilized to change the spacing between the upper and lower mold members in the bending station to adjust the bending pressure applied to the glass sheets. Furthermore, the parameters are utilized to change the speed of the conveyor sections in order to vary the time that the glass sheets are in the furnace and thus the amount of heat imparted to the glass sheets.

The present invention relates generally to an apparatus for processing glass sheets and, in particular, to an apparatus for heating and bending glass sheets.
One process that has been successful in producing bent, tempered sheets of glass, such as are commonly used in glazing closures for automobiles and the like, is the horizontal press bending technique. This technique generally includes heating pretrimmed flat sheets of glass to their softening or bending temperatures by advancing them on a roll conveyor through a heating furnace, bending the heated sheets to a desired curvature or shape between a pair of complementary mold members and then tempering the same by chilling the bent sheets in a controlled manner to a temperature below the annealing range of glass.
It should be appreciated that the glazing closures formed by the above-described process must be bent to precisely defined shapes as dictated by the configuration and size of the openings and the overall styling of the vehicles in which the closures are to be installed.
Moreover, the glazing closures must be properly tempered to increase their resistance to damage resulting from impact and, in the event of breakage, to fragment into relatively small harmless particles as opposed to the large, jagged, potentially dangerous pieces otherwise resulting from untempered glass sheets when broken. Additionally, the bent and tempered glazing closures must meet stringent optical requirements whereby they are free of surface defects and optical distortions that would interfere with clear vision therethrough.
Probably the single most significant factor in meeting all of the above-mentioned requirements resides in heating the sheets to an optimum temperature level during the heating phase to properly condition the glass sheets for further processing. If the heated sheet exits the heating furnace at a relatively cool temperature for example, it will not be sufficiently soft for expedient and proper bending. Moreover, it will not retain the necessary heat required for subsequent tempering. On the other hand, if the sheet leaving the furnace is overheated, it will be extremely pliable with attendant loss of deformation control and will tend to sag out of the desired shape beyond the close tolerances prescribed. Also, overheating tends to degrade the surface quality of the finished product as a result of heat stains, roll marking, pitting and the like. While the optimum temperature range to which the sheets must be heated for satisfactory further processing can be readily calculated, problems are encountered in consistently reaching this desired temperature level and maintaining a multiplicity of glass sheets within such range in a mass production operation. This is due to the inherent, although slight, temperature variations generated by the irregular heat output of the heating elements, whether gas fired or electrical resistance elements, within the furnace and from other extraneous sources which influence the temperature of the heating atmosphere. In any event, it has been found that the temperatures of successive sheets exiting the furnace, as monitored by sophisticated temperature measuring devices, varies frequently and sometimes from sheet to sheet.
Attempts have been made to solve this problem by varying the thermal input to the heating elements in accordance with glass temperature variations from a desired level. However, these attempts have not been entirely satisfactory because of a lagging heat input response, i.e., a time delay before the adjusted thermal input is adequately reflected in the heating atmosphere and imparted to the advancing glass sheets. Other attempts involve manually adjusting the rate of conveyor speed to compensate for temperature variations. However, it is virtually impossible to manually effect the necessary adjustments accurately in a minimum of time because of human error and/or miscalculations, thus seriously impairing efficiency in a mass production operation. Moreover, the complete concentration and constant surveillance required of the operator contributes significantly to fatigue, further increasing the possibilities of human error and poor judgment.
One attempt to control the temperature of glass sheets is shown in U.S. Pat. No. 4,071,344. This patent shows a method and apparatus for controlling the temperature of glass sheets moving through a furnace by automatically varying the heat exposure time of the sheets in the furnace in accordance with temperature variations from a desired level detected in heated sheets exiting the furnace. The sheets are supported in a substantially horizontal plane and moved in a generally horizontal path through the heating furnace at a preselected rate of speed. The individual temperatures of a given series of the heated glass sheets exiting the furnace are measured and the average temperature deviation of the series of a desired temperatures is determined. The rate of speed of the glass sheets in the furnace is varied in accordance with the amount of deviation of the average temperature from the desired temperature to vary the duration of time the sheets moving through the furnace are exposed to heat and thus varying the duration of speed change in accordance with the amount of deviation of the average temperature from the desired temperature.


A process for protecting nonstable or moderately stable, cohesionless to slightly cohesive geologic formations, in particular, in tunnel construction, in which drill holes are first made by boring into the formation and, following completion of the boring, the drilling rod is removed. During this removal a hardenable injection material is forced into the drill hole, whereby, using a drilling rod, a pointed rod or anchoring element is placed in position in the boring. This element remains in the boring during removal of the drilling rod, and is solidly connected to the formation by the injection material.

1. Field of the Invention
The present invention relates to a process for protecting nonstable or moderately stable, cohesions to slightly cohesive geologic formations, in particular, in tunnel construction, in which drill holes are first made in the formation and, following completion of the borings, the drilling rods are removed, and a hardenable injection material is forced into the drill hole, during the removal.
2. The Prior Art
In cavity construction, extended drilling in soft or unconsolidated rock is either avoided or executed by means of costly machinery such as shields, hydroreinforced breasts or the like or by means of extensive injection procedures or freezing methods.
An additional complex and expensive process comprises the combination of compressed air and the new Austrian method of tunnel construction. These processes have the drawback that expensive mechanical means are required for their implementation. Especially with shorter tunnels or in the eventuality that only smaller sections of a longer tunnel require more labor- and cost-intensive reinforcement measures owing to the presence of unconsolidated rock, utilization of such processes is not justified by the attendant expense.
Injection boring anchors and preliminary breast boards with preliminary breast sheets, preliminary breast pointed bars and the like constitute another variation of advance protection known in the art. These safety provisions can be set up on site with relatively low equipment costs. A drawback of the injection boring anchor is the fact that the drill bit remains together with the anchoring element inside the borehole and is consequently lost. This results in relatively high consumption of expensive materials.
In addition, injection bar methods (alluvial pointed bars) are known in the art according to which, following construction of the borehole, the drilling rod is removed from the drill hole and an anchoring element or pointed bar inserted which is cast into the borehole by means of a hardenable injection material. This process exhibits the disadvantage that several operation cycles are required for its implementation, with the result that work progress is necessarily slow. Additionally, the drill hole can collapse between the removal of the drilling rod and introduction of the alluvial pointed bar, necessitating additional time consuming operations.


The present invention encompasses novel synthetic peptide analogs that are antagonists to Substance P, substance P like peptides and related peptides and are useful for the treatment of cancer. The invention particularly relates to the design and synthesis of the novel substance P antagonist analogs incorporating xcex1,xcex1-dialkylated amino acids in a site specific manner. The invention encompasses methods for the generation of these peptides, compositions containing these peptides and pharmacological applications of these peptides specifically in the treatment and prevention of cancer.

The present invention encompasses novel synthetic peptide analogs that are antagonists to Substance P, substance P like peptides and related peptides and are useful for the treatment of cancer. The invention particularly relates to the design and synthesis of the novel substance P antagonist analogs incorporating xcex1,xcex1-dialkylated amino acids in a site specific manner. The invention encompasses methods for the generation of these peptides, compositions containing these peptides and pharmacological applications of these peptides specifically in the treatment and prevention of cancer.
Substance P is one of the main members of the tachykinin family. The tachykinins are mammalian regulatory peptides and are present in the central and peripheral nervous systems, and in gut endocrine cells. Substance P was the first gut neuropeptide to be discovered. It is a 11 residue neuropeptide of the following sequence:
Arg-Pro-Lys-Pro-Gln-Gln-Phe-Phe-Gly-Leu-Met-NH2
(SEQ ID NO: 1)
Substance P regulates gastrointestinal motility, increases blood flow in the gut, stimulates secretion of the pancreas, salivary glands, small intestines and inhibits acid secretion. In the central nervous system, tachykinins play a role in the sensory nervous pathways and in motor control. (Dockray, G. J., 1994, 401 Gut peptides: Biochemistry and Physiology, Raven Press Ltd, New York).
The role of Substance P in cancer has been well recognized particularly in small cell lung cancer. Small cell lung cancer (SCLC) cell growth is sustained by multiple autocrine and paracrine growth loops involving neuropeptides. In the search for novel antiproliferative agents for small cell lung cancer the first substance P antagonist to be studied was [D-Arg1, D-Pro2, D-Trp7,9, Leu11] substance P (Antagonist A). Substance P is structurally unrelated to bombesin/GRP and has no bombesin/GRP antagonist activity; antagonist A was found to block the secretory effects of bombesin on a pancreatic preparation, diminish bombesin/GRP binding to its receptor and inhibit mitogenesis in Swiss 3T3 cells (Jensen et al., 1984, Nature, 309; 61-63; Zachary and Rozengurt, 1986, Biochem. Biophys. Res. Commun., 137;135-141). However it did not affect mitogenesis induced by polypeptide growth factors, such as platelet-derived growth factor and epidermal growth factor. Among other congeners of substance P tested for bombesin/GRP antagonism, two compounds with inhibitory activity were identified: antagonist D, [D-Arg1, D-Phe5, D-Trp7,9, Leu11] substance P, and antagonist G [Arg6,D-Trp7,9, MePhe8] substance P(6-11). Antagonist D was shown to be five fold more potent than antagonist A in preventing the cellular effects of bombesin/GRP and vasopressin in mouse 3T3 cells and in inhibiting the growth of SCLC cells in serumfree medium. Overall, in Swiss 3T3 cells both antagonists were demonstrated to have in common the ability not only to inhibit the effects of bombesin/GRP but also the effects of other neuro-peptides, including vasopressin, bradykinin, endothelin, and substance P. This is also reflected by data showing that antagonist G is ten fold less potent than antagonist D in blocking bombesin/GRP mediated mitogenesis in Swiss 3T3 cells and it is almost as potent as antagonist D in inhibiting SCLC proliferation in vitro. Antagonist D inhibited proliferation of H-510 and H-69 SCLC cells in liquid culture and in semi-solid media (IC50=5 xcexcM). Colony formation stimulated by multiple neuropeptides including vasopressin and bradykinin was also blocked by Antagonist D (Seckl, M. J. et al.,1997, Can Res, 57(1):51-4). In addition, antagonist G showed inhibition of SCLC xenografts in vivo (Wolf P. J. and Rozengurt, E., 1990, Can. Res., 50(13):3968-73; Everard, M. J., et al., 1993, Eur J Cancer, 29A(10):1450-3; Br J Cancer, 1992, 65(3):388-92)). Reeve, J. G. and Bleehen, N. M. (Biochem. Biophys. Res. Commun.,1994, 199(3):1313-19) found that treatment of lung tumor cells with Antagonist D caused a concentration-dependent loss of cell viability which was accompanied by the onset of apoptosis as defined by cytological criteria and DNA fragmentation.
Short-chain SP antagonist viz.pHOPA-D-Trp-Phe-D-Trp-Leu-Leu-NH2 (Analog R) (SEQ ID NO: 2) and its analogs were studied by the Hungarian group and were found to inhibit the proliferation of H69 SCLC cells both in vitro and in xenografts in vivo in nude mice (Int. J. Cancer, 1995,60(1):82-7). In a further extension of the work, the C-terminal peptide bond was replaced by a methylene-amino (pseudopeptide) bond. Substance P analogues: D-MePhe-D-Trp-Phe-D-TrpLeu(psi)-(CH2NH)-Leu-NH2) (SEQ ID NO: 3); Analog 6 and D-MePhe-D-Trp-Phe-DTrp-Leu-MPA (SEQ ID NO: 4): Analog 7, inhibited SCLC pro-liferation more effectively than Analog R (6: IC50=2 xcexcM; 7: IC50=5 xcexcM and R: IC50=10 xcexcM). Moreover, Analog 6 inhibited the respiratory activity of SK-MES 1 epithelial type of lung carcinoma cells in proliferating but not in the quiescent state suggesting that the anti-proliferative effect of these compounds is not due to simple cytotoxicity and these short chain SP analogues may be promising candidates as therapeutic agents in the treatment of SCLC (Nyeki, O. ,et.al., 1998, J. Pept. Sci, 4(8): 486-95). Antagonist D and its role in cancer has been described in the U.S. Pat. No. 5,434,132 and WO 88/07551.
The present invention describes peptide analogs of substance P, the preparation, and use of peptide analogs of substance P especially the Antagonist D of substance P using constrained amino acids and their use thereof for cancer therapy, alone, or in combination or as an adjunct to cancer chemotherapy.
The design of conformationally constrained bioactive peptide derivatives has been one of the widely used approaches for the development of peptide-based therapeutic agents. Non-standard amino acids with strong conformational preferences may be used to direct the course of polypeptide chain folding, by imposing local stereochemical constraints, in de novo approaches to peptide design. The conformational characteristics of xcex1,xcex1-dialkylated amino acids have been well studied. The incorporation of these amino acids restricts the rotation of xcfx86,xcexa8 angles within the molecule, thereby stabilizing a desired peptide conformation. The prototypic member of xcex1,xcex1-dialkylated aminoacids, xcex1-amino-isobutyric acid (Aib) or (xcex1,xcex1-dimethyl glycine has been shown to induce (3-turn or helical conformation when incorporated in a peptide sequence (Prasad and Balaram, 1984, CRC Crit. Rev. Biochem.16, 307-347; Karle and Balaram, 1990 Biochemistry, 29, 6747-6756). The conformational properties of the higher homologs of xcex1,xcex1-dialkylated amino acids such as diethylglycine (Deg), di-n-propylglycine (Dpg) and di-n-butylglycine (Dbg) as well as the cyclic side chain analogs of a,a-dialkylated amino acids such as 1-aminocyclopentane carboxylic acid (Ac5c), 1-amino-cyclohexane carboxylic acid (Ac6c), as 1-aminocycloheptane carboxylic acid. (Ac7c) and as 1-aminocyclooctane carboxylic acid (Ac8c) have also been shown to induce folded conformation (Prasad, S. et al., 1995 Bioployrners, 35, 11-20; Karle, L. L.,et al., 1995, J. Amer. Chem. Soc.,117, 9632-9637). xcex1,xcex1-Dialkylated amino acids have been used in the design of highly potent chemotactic peptide analogs (Prasad, S. et al., 1996 Int. J. Peptide Protein Res. 48, 312-318.) However, the applicants are not aware of any prior art for the synthesis of novel peptide analogs, encompassed in the present invention, particularly the synthesis of such substance P peptide analogs, containing xcex1,xcex1-dialkylated amino acids. Moreover, the use of such constrained amino acids for the design of peptides possessing anti-neoplastic activity is also unknown in any previous prior art. The present invention exploits the conformational properties of such xcex1,xcex1-dialkylated amino acids for the design of biologically active peptide derivatives of substance P with specific anticancer activity. Furthermore in the prior art it has been shown that lipophilazation of bioactive peptides improves the stability, bioavailability and ability to permeate biomembranes (Dasgupta, P et al; 1999, Pharmaceutical Res. 16, 1047-1053; Gozes, I. et al., 1996, Proc. Natl. Acad. Sci. USA, 93, 427-432).
The present invention also includes synthesized peptide derivatives having N-terminal alkanoyl groups from 2-18 carbon atoms with improved anticancer activity.
In the formula (I) below and throughout the specification and claims the amino acids residues are designated by their standard abbreviations. Amino acids denote L-configuration unless otherwise indicated by D or DL appearing before the symbol and separated from it by hyphen.
The following abbreviations are also used in this application:
The present invention comprises polypeptides of the following general formula:
X-D-Arg-Pro-Lys-Pro-D-Phe-Gln-D-Trp-Phe-D-Trp-Leu-R-NH2
wherein,
X is acetyl or straight, branched, or cyclic alkanoyl group from 3 to 18 carbon atoms, or is deleted;
R is Aib, Deg, Dpg, AcSc or Ac6c; or R is a hydrolyzable carboxy protecting group; or a pharmaceutically acceptable salt of the peptide.

Substance P analogs for the treatment of cancer


A fluidized bed pyrolytic carbon coating apparatus (1) is provided for coating substrate surfaces with pyrolytic carbon. The preferred coating apparatus (1) includes a fluidized bed reactor (10) having a reactor chamber (22), a gas feed inlet (24), an exhaust gas outlet (26), a source (12) of process feed gas and a gas line (14) through which the process feed gas can pass from the source (12) of process feed gas to the gas feed inlet (24) and into the reactor chamber (22). The gas line (14) includes an actuator (20) having a timing circuit (37) which acts to vary a rate of flow of process feed gas through the gas line (14) into the reactor chamber (22) such that the rate of flow into the reactor chamber (22), cycles regularly and consistently over a period of time so as to create a pulsating gas flow and a pulsation effect upon the fluidized bed within the reactor chamber (22).

Pyrolytic carbon used to coat parts of heart valve prostheses is formed as a coating on substrates in high temperature deposition processes. A fluidized bed reactor is generally used for the coating operation. In the deposition process a gas stream, consisting of a mixture of hydrocarbon gas (e. g. propane, acetylene, methane, propylene or the like) and an inert gas (e. g. helium, argon, nitrogen or the like), is metered through a vertical heated graphite chamber containing a bed of spherical particles or beads. The shape of the graphite reactor chamber at the gas entrance is generally conical. The gas stream fluidizes or levitates the bed of particles along with valve component substrates suspended within the bed and a part thereof. Pyrolytic carbon coating apparatii of this kind are disclosed in U.S. Pat. Nos. 5,262,104; 5,305,554; 5,332,337; 5,328,720; 5,284,676; 5,328,713; 5,514,410; 3,676,179; 3,677,795 and 3,977,896, each of which is incorporated herein by reference.
The pyrolytic carbon used in heart valves is a form of high density, high wear resistant, high strength carbon. From the biomedical point of view it is noteworthy because of its biocompatibility. From scientist""s perspective it is a high technology material which is prepared as a coating on substrates in a fluidized bed and elevated temperature deposition process. In the deposition process a suitable hydrocarbon gas (e. g. propane ) along with neutral gas (e. g. helium, argon and/or nitrogen) is metered through a vertical heated graphite chamber containing a bed of granular particles. The shape of the graphite chamber at the entrance is generally conical. This gas stream fluidizes, i. e. levitates and agitates the bed of particles along with any valve substrate components suspended in the bed. The fluidized bed is generally heated in one manner or another, preferably by furnace. The heated bed, in turn, heats the gases. When sufficiently hot, the reactant gases, such as propane and/or other hydrocarbon gases, pyrolyze, thereby dehydrogenating, and form pyrolytic carbon as a solid coating. The pyrolytic carbon coating deposits on the suspended valve components as well as the bed of granular particles. The action of the fluidized bed causes the valve components to continuously circulate through out the bed resulting in coating over their entire surface.
According to the disclosure provided in U.S. Pat. No. 3,977,896 to Bokros et al. (Bokros ""896 patent), one of the key parameters which determine the structure of pyrolytic carbon, is the ratio of available deposition surface area relative to the volume of hot zone occupied by the fluidized bed of particles. In the ""896 patent disclosure, this parameter is used as a variable for characterizing carbon coating processes. It is believed by the present inventor, that pyrolytic carbon deposited on levitated valve components has certain desirable properties when the surface area of the particles is fairly high when compared to the surface area of the valve components. When such sub-millimeter particles are being coated along with valve components in a fluidized bed, the total surface area of the particles begins to increase significantly as the diameters of the particles increase. However, because of the substantial growth of surface area of the particles, most of the carbon deposition is deposited on the particles rather on the valve components. The coating thickness thus obtained on the valve components is fairly limited. The coating thickness required for manufacture of heart valves is generally higher than possible via the process described above. In order to overcome this difficulty, researchers developed a technique in which small size particles were fed to the hot zone and large coated particles were removed from the coating chamber during the deposition process without causing undue disruption to the process. The Bokros ""896 patent is probably the first patent that disclosed the concept of feeding the small size beads and withdrawing the larger coated beads during the deposition process. This technique made it possible to achieve thicker coatings required for heart valve applications.
The Bokros ""896 patent describes a number of process parameters for carrying out coating processes. A detail review of specific items pertinent to the fluidized coating reactor apparatus and the process parameters disclosed therein is provided below.
Particle Feed and Purge Systems
As mentioned above, the Bokros ""896 patent discloses an apparatus for carrying out coating processes. The patent mentions process parameters for depositing coatings having desirable properties, and feed and withdrawal systems for achieving relatively thick (at least 150 micrometers or microns) coatings. Coating thicknesses greater than 150 microns are believed to be possible by lengthening the duration of coating period. The Bokros ""896 patent discloses the idea, the apparatus, and a method of feed and withdrawal of particles. The particle withdrawal is carried out by utilizing a small diameter tube that is placed alongside a wall within the deposition chamber. A neutral gas is continually passed upward through this tube. By adjusting the upward flow rate of neutral gas, coated particles of varying quantities are removed from the fluidized bed. The height of the tube is less than 5 cm above the conical section of the chamber. The internal diameter of the withdrawal tube is such that a helium gas flow of 4 liters per minute prevents removal any particles from the fluidized bed. The withdrawn particles are volumetrically metered. By adjusting the upward flow rate of neutral gas through the withdrawal tube, a purge rate at 90 to 150 cubic centimeters per hour can be achieved. The feed particles are fed via a similar size tube placed along the cylindrical wall of the chamber. The particles are fed intermittently or continuously near the fluidized zone from the top. The feed tube is continually purged with sufficient downward flow of neutral gas.
Source Materials
The Bokros ""896 patent discloses several hydrocarbon gases such as methane, propane, ethane, butane, acetylene and propylene for depositing pyrolytic carbon coating. Helium, argon and nitrogen gas are used as neutral gases. The examples given describe use of propane and helium gases for depositing pure and silicone alloyed pyrolytic carbons.
In each of these systems, the pyrolytic carbon comes from the propane or other hydrocarbon gas which enters the reactor and is deposited on the valve component substrates by an endothermic chemical decomposition reaction described for example, in the systems employing propane, by the reaction provided immediately below:
C3H8(g)298xc2x0 Kxe2x86x923C(s)+4H2(g), xcex94HR=24.82 Kcal/gmole
The reactor chamber is heated by an electrical heating element which in turn heats the gases. When the gases are sufficiently hot, the hydrocarbon gas breaks up or decomposes by a process called pyrolysis to form a pyrolytic carbon coating on the beads and on the valve component substrates, and gaseous hydrogen. The helium or other inert gas serves as an inert carrier/fluidizing gas. The inert, or neutral, gas does not react in the decomposition reaction. The pyrolytic carbon coating is deposited on the suspended valve component substrates, as well as on the beads, under suitable conditions. The action of the fluidized bed generally causes the valve components to circulate through the entire bed, resulting in coating over all exposed surfaces.
In the reactors presently used to coat components of heart valves, the gas stream from the gas inlet into the reactor is believed to be a steady stream of gas. The stream of gas may be metered, but it will still be a steady stream having a constant flow. At times, such a system will malfunction when two or more of component parts become engaged with one another against the inner wall of the reactor, thereby disrupting the bed by immobilizing a portion of it, and thereby changing the coating parameters of the xe2x80x9crunxe2x80x9d such that a consistent coating process cannot be maintained.
Furthermore, in order to obtain consistent coating on valve components or the like coated in consecutive or non-consecutive batch operations, strict attention must be paid to keeping all parameters exactly the same. This is a difficult task at best. Indeed, it is believed that consistent coating in pyrolytic coating processes cannot be obtained without at least some variance from batch to batch with the prior art coating apparatus described in the Bokros ""896 patent, or those generally used at present for batch process coating processes. This is because each reactor has its own irregular frequencies which change with the time of the run as the suspended substrates and beads are coated. New uncoated beads are metered into the bed and coated beads are removed from the bed in order to maintain a generally consistent average weight and density for the beads, but the weight and density of the substrates increase throughout the run. This results in alterations in fluidized bed action within the reactor, and leads to undesirable inconsistencies in the coating deposited on the various substrates during the run.
Accordingly, it will be appreciated that there is a need for an efficient pyrolytic carbon coating apparatus or system for providing a consistent coating of pyrolytic carbon on valve components and the like. The present invention provides advantages over the prior devices and prior methods used to coat valve components, and also offers other advantages over the prior art and solves other problems associated therewith.
The pyrolytic carbon coating apparatus of the present intention includes a fluidized bed reactor having a reactor chamber, a gas feed inlet, and an exhaust gas outlet, a source of process feed gas, preferably including a mixture of gaseous hydrocarbons and inert carrier gases, more perferably including gases selected from the group consisting of gaseous hydrocarbons, inert carrier gases and mixtures thereof, and a gas line through which the process feed gas can pass from the source of process feed gas to the gas feed inlet and into the reactor chamber. The fluidized bed reactor is of a type which generally permits the levitation or fluidization of substrates in a pyrolytic carbon coating environment where gaseous hydrocarbons within the process feed gas is decomposed at elevated temperatures in order to coat surfaces of fluidized substrates with pyrolytic carbon. The gas line of the present invention includes an actuator which varies the rate of flow of process feed gas into the reactor chamber, such that the flow of process feed gas, through the gas line to the reactor chamber when the reactor chamber is occupied by a fluidized bed including at least one or preferably plurality of substrates to be coated by pyrolytic carbon, cycles regularly over a consistent period of time from a higher flow rate to a lower flow rate and vice versa, so as to create a pulsating gas flow and a pulsation effect upon the fluidized bed within the reactor chamber. The preferred actuator includes a bypass line and a main line through which process gas can flow. The bypass line includes a metering valve, preferably a needle valve, which can be used to restrict the flow of process gas through the bypass line. The main line includes a gas filter, preferably a high purity gas filter, through which the process gas flows prior to flowing through a switch valve, preferably an oscillating solenoid valve, which opens and closes in a regular cycle thereby alternately stopping and permitting the flow of process gas through the main line. The bypass line and the main line both diverge from and subsequently rejoin the gas line to direct a pulsating flow of process feed gas through the gas line into the reactor chamber having a flow rate which regularly cycles from a higher flow rate to a lower flow rate and vice versa. The apparatus enhances the ability of the user to provide a consistent coating of pyrolytic carbon on different sizes and types of component substrates. This is particularly desirable for individual components of heart valve prostheses.
The present pyrolytic carbon coating apparatus allows one to control the frequency and amplitude of the pulsating feed gas flow rate. As the needle valve in the bypass line is moved toward a closed position, thereby decreasing the rate of flow through the bypass line, the difference between the higher flow rate and the lower flow rate increases. As the needle valve in the bypass line is opened, thereby increasing the rate of flow through the bypass line, the difference between the higher flow rate and the lower flow rate decreases. The frequency and the amplitude can be controlled in a manner which allows this use to produce coated component parts having consistent coating parameters from one batch to another. A sufficient flow of steady process gas through the bypass line is maintained so as to avoid the collapse of the fluidized bed.
It is an object of the present invention to provide a reactor in which gaseous hydrocarbons are efficiently decomposed to form a pyrolytic coating on substrate surfaces which is of greater quality than that which has been previously available, and which can be applied to the substrate surfaces more evenly and consistently over a series of batch coating processes, while creating less soot buildup within the reactor chamber.

Pyrolytic carbon coating apparatus having feed gas actuator


In the pier mooring for a boat a rectangular inner section is provided which serves as the land connection. A first short side and an outer part of the pier mooring is affixed to a second outer short side of the inner part of the structure. The outer part is formed as a parallel trapezium with the non-parallel side forming an angle of between 70 to 120 degrees. The non-parallel sides are provided with extensions which have outer ends which employ locking structure to affix the boat to be moored therebetween by means of lines running from the outer ends to either end of the boat.

The present invention relates to an improved construction of a landing-stage or pier for small boats or yachts.
Due to the ever increasing number of small boats and yachts there is a demand for improved landing or mooring stages or piers which are easy to raise or assemble and permits a simplified mooring. A pier for boats of the above-mentioned type usually consists of a plane leading from the land out into the water to the required depth. Boats are usually tied to such a pier with the use of a buoy in the water at a distance from the pier, the buoy being kept in position with an anchor, stone or similar object. The boat is tied between the buoy and the pier. One pier can accomodate a number of boats depending on its size. However, such moorings are relatively expensive, especially since the chain which customarily is used to connect the buoy with the anchor stone will be corroded by rust-formation and has a limited length of life, usually 3 - 5 years. Also, such construction tends to be destroyed by ice formed during the winter period


A method for forming a large number of labels from a base sheet on which markings and symbols are imprinted on rows and columns. This base is reinforced with a transparent sheet cemented to the front of the base and/or a backing foil or material cemented to the rear face of the base. Perpendicular edges are cut, parallel to the rows and perpendicular to the columns respectively. Cuts are then made making individual strips. The strips are realigned, connected together and cuts are made, separating the reconnected base into a series of labels.

Many very different ways of preparing labels are known. It can be done by engraving the desired symbols on a carrier material of appropriate shape or by providing a piece of roughened plastic foil with the symbols--for example, by putting the symbols on with a typewriter and then cementing the piece of foil bearing the symbols onto a carrier foil. It can also be done by cementing the symbols on a transparent plastic foil, with a varnish which is or becomes transparent at the latest after hardening and which has an index of refraction sufficiently similar to that of the plastic foil. The varnish may be sprayed or painted on the foil. Suitable varnishes with the required qualities are known, but plastic varnishes are recommended, especially those which are irreversible when hardened. For instance, a two-component varnish may be used, such as the well-known "DD" varnishes which, when hardener is added, cross-link to form a plastic coating.
The method of preparing a rather large number of labels by imprinting the symbols on individual backings cut to size by the silk-screen process is also known. However, that is a method which is only useful when a large number of labels, all bearing the same symbols or the same lettering, is required.
Another method for preparing a number of labels consists of putting all of the desired symbols or lettering on one base--with a typewriter, with letters which are applied by rubbing, or the like--and then cutting up the base to make the individual labels. It is relatively easy to perform such a cutting process if the base is a sheet of paper or a thin plastic foil. However, the cutting becomes difficult if the base is relatively stiff, or, if after the symbols have been put on, the base is reinforced by cementing on a relatively stiff plastic foil covering the symbols or by cementing a backing foil onto the back of the base. For practical purposes, a base reinforced in that way cannot be cut up in the usual manner so that all labels are of the same size and the lettering is located centrally on all labels and the edges of the individual labels are exactly straight and run exactly parallel and/or perpendicular to each other.
All of these methods of preparation have a disadvantage when they are used in the preparation of individual labels for the many uses to which they can be put, e.g., for switchboards and other installations, where a large number of labels of the same size, but with different lettering, is required.
Therefore, it is the object of the invention to provide a method which makes it possible to prepare a large number of individual labels whose symbols or letters are first put on a base which is common to all labels and which thereafter is cut in such a way that the edges of the individual labels are exactly parallel and/or perpendicular to each other, with the lettering being located centrally on the individual labels if that is desired.
A method for preparing a large number of labels has been devised in which the symbols for the labels are put on a base arranged in marked rows and columns, a transparent plastic foil is then cemented onto the face of the base and/or a backing foil or material is cemented onto the back of the base. The base which has been reinforced in that way is then cut up in one of two methods. One method is to first cut the base so that two adjoining edges of the base, which is bound with the plastic foil and/or the carrier foil or material, are cut at right angles to each other, so that one edge runs parallel to the rows on which the symbols have been placed and the other edge runs perpendicular to those rows. The base is then laid with one of its edges against a bearing surface and cut along the markings which are parallel to the cutting edge (perpendicular to the edge bearing on the bearing surface). The resulting strips made in this way are reassembled in the same sequence and aligned by means of a carrier foil or material. The reassembled base is then laid with its second adjoining edge on a bearing surface and cut along the markings (perpendicular to said second adjoining edge). A second method is to cut the base row by row according to the markings, align the strips made in this way centrally with respect to a column, connect the strips by means of a carrier material in the area of that column and then cut along the edges of the column. The remaining strips portions are then aligned centrally with respect to their respective columns, connected by means of a carrier material and cut.
Thus, in accordance with the methods of the invention, a base is made with markings and symbols which is reinforced by the plastic foil and/or the backing foil or material in such a way that the inaccuracies which arise when cutting in one direction--say, cutting row by row--are not added in with or onto the inaccuracies which arise when subsequently cutting perpendicular to the first cutting operation. Specifically in the case of the first-mentioned method, when the strips resulting from the first cutting operation are in the same sequence and alignment by means of the carrier material and are joined together again, what results is the original form of the base, and consequently the individual labels and the symbols and letterings of the individual labels lie in the same positions with respect to each other again. Thus a second cutting can take place without the first cutting having any influence on the shape, accuracy and direction of the second cutting, and consequently having any influence on the label edges resulting from the second cut.
In the second method, a row by row cutting takes place first, and then the individual columns are aligned centrally. This can be accomplished by laying them on a grating for example. Then all strips of a column aligned in that way are bound by means of the carrier foil or material, so that a cutting in the direction in which the columns extend can again take place without the course of such a cut being influenced by the course of the cuts which were previously made in the direction in which the rows extend. Preferably, the carrier foil or material used for reassembling the strips can itself be pliable--for example, the carrier foil or material can consist of a transparent plastic foil. If that is so, the cementing is naturally carried out in such a way that the carrier foil or material can also easily be pulled off again. Consequently, the labels of one column adhere to the carrier material after the cutting has taken place so that the user can select the desired label very easily and detach it from the carrier material in order to place it in the desired location.

Method for preparing a plurality of labels