A telecommunications system having a format converter provides bi-directional communications between TDM signals on one side and ATM signals on the other. An ATM aggregate receives and transmits ATM signals, and a TDM interface receives and transmits TDM signals. The format converter has an ATM bus and a TDM bus connected to their respective interfaces, and service-specific adapters are connected between the ATM bus and the TDM bus.

1. Field of the Invention
The invention relates generally to telecommunication systems and more particularly to development of such systems to allow use of different communication formats.
2. Description of the Related Art
The most common communication format for telecommunication systems is time division multiplexing (TDM) which is a continuous bit rate service concatenated as multiples of 64 kb/s channels. The TDM technique is particularly effective for voice communication because it is connection-oriented, i.e. a connection link is established initially and is maintained throughout a communication session. Also, the speed and reliability are sufficient for voice.
However, TDM is not particularly effective for data traffic because it is inflexible and does not accommodate the "bursty" nature of data very well. It was for this reason that packet-based techniques have been developed for data communication. For example, the Internet Protocol (IP) technique is used for much Internet service provider (ISP) and local area network (LAN) communication. This technique uses variable-length packets, each of which is independently routed. This means that the technique is not connection-oriented and the bandwidth for a call is not guaranteed for the duration of the call. The general view is that voice subscribers would not tolerate the ensuing unpredictability of call quality. Also, the equipment required for processing to achieve the required speed for voice is quite complex. Therefore, while the IP technique is an approach which may be used to some extent in the future for both voice and data telecommunication networks, problems need to be overcome.
Another packet-based technique is the asynchronous transfer mode (ATM) technique. This has the advantages that it is packet-based and so can handle bursty data traffic well, and is also connection-oriented. In this technique, data is transmitted in fixed-length packets which are typically 53 Bytes in length, having a 48 Byte payload and a 5 Byte header. The header comprises a virtual path identifier (VPI) and a virtual channel identifier (VCI). According to the ATM standard, the cell transfer technique is common to all services and therefore a single ATM stream of cells can include a wide range of different services. Because the cells have a fixed length, timing and control is more predictable. On the other hand, packets in the IP technique are often much longer than ATM cells.
Packet-based techniques are radically different from the TDM technique and therefore it is not practical for a telecommunication operator to change over in a short period of time. In order to introduce packet-based techniques such as ATM, adaptation processes have been developed which are service-specific as different reconstruction techniques are involved. This has led to a large degree of complexity and expense.
It is also known to provide a hybrid system in which TDM and ATM signals are combined in a frame for communication over a link. Such an arrangement is described in PCT Patent Specification No. WO 97/18649 (DSC Communications Corp.). While this arrangement is suitable for specific application areas such as provision of services to a home, it does not appear to be efficient enough for telecommunication networks. This is particularly the case if a number of different services are involved.
European Patent Specification No. EP614324 (Nippon) describes a system for separate TDM/ATM and ATM/TDM conversion. However, this system appears to be quite complex and to be difficult to scale up for increased transaction volume capacity.


Indole derivatives represented by formula (I):

The present invention relates to indole derivatives.
More specifically, the present invention relates to indole derivatives represented by formula (I):
(wherein all symbols have the same meanings as described below), a process for the preparation of the same and use thereof.
Prostaglandin D (hereinafter referred to as xe2x80x9cPGDxe2x80x9d) are known as a metabolite in the arachidonic acid cascade, and are known to have effects of bronchoconstriction, vasodilatation or vasoconstriction and platelet aggregation inhibition. PGD is considered to be produced from mast cells, and the increase of PGD concentration has been recognized among systemic mastocytosis patients (New Eng. J. Med., 303, 1400-1404 (1980)). Also, PGD is considered to relate to neuro activities, especially, sleep and hormone secretion. Furthermore, there are reports suggesting participations in platelet aggregation, glycogen metabolism, ocular tension adjustment and the like.
PGD shows its effects by binding to a DP receptor which is a receptor thereof. A DP receptor antagonist binds to and is antagonistic to its receptor so that it can inhibit the function of PGD. Accordingly, it is considered to be useful for the prevention and/or treatment of diseases, for example, allergic diseases such as allergic rhinitis, allergic conjunctivitis, atopic dermatitis, bronchial asthma, food allergy, etc.; systemic mastocytosis; disorders due to systemic mastocyte activation; anaphylactic shock; bronchoconstriction; urticaria; eczema; allergic bronchopulmonary aspergillosis; inflammatory paranasal sinus; nasal polyp; hypersensitive angitis; eosinophilia; contact dermatitis; diseases accompanied with itching, such as atopic dermatitis, urticaria, allergic conjunctivitis, allergic rhinitis, contact dermatitis, etc.; secondary diseases caused by behaviors (scratching behaviors, beating, etc.), such as cataract, retinal detachment, inflammation, infection, sleep disorder, etc.; inflammation; chronic obstructive pulmonary disease; ischemic reperfusion disorder; cerebrovascular disorder; pleuritis complicated by rheumatoid arthritis; ulcerative colitis; and the like. Moreover, it is considered to relate to sleeping and platelet aggregation and to be useful for these diseases.
Some DP receptor antagonists are known until now, and BW-A868C represented by formula (A) is considered to be the most selective:
Also, recently, DP receptor antagonists which are thromboxane derivatives have been published in WO 98/25915, WO 98/25919, WO 97/00853, WO 98/15502 and the like.
On the other hand, as a compound similar to the compound of the present invention, an indole compound represented by formula (B) is known as a synthetic intermediate (J. Heterocyclic Chem., 19, 1195 (1982)).
The present inventors intensively studied to find a compound which specifically binds to DP receptor and show an antagonistic activity and found that the object could be attained by indole derivatives represented by formula (I), and thus the present invention has been completed.
That is, the present invention relates to an indole derivative represented by formula (I):
wherein R1 represents hydroxy, C1-6 alkoxy, or NR8R9, in which R8 and R9 each independently represents a hydrogen atom, C1-6 alkyl, or SO2R13, in which R13 represents C1-6 alkyl, a C3-15 saturated or unsaturated carbocyclic ring or a 4- to 15-membered heterocyclic ring containing 1 to 5 nitrogen atom(s), sulfur atom(s) and/or oxygen atom(s);
R2 represents a hydrogen atom, C1-6 alkyl, C1-6 alkoxy, C2-6 alkoxyalkyl, a halogen atom, amino, trihalomethyl, cyano, hydroxy, benzyl, or 4-methoxybenzyl;
R3 represents a hydrogen atom, C1-6 alkyl, C1-6 alkoxy, a halogen atom, trihalomethyl, cyano, or hydroxy;
R4 and R5 each independently represents a hydrogen atom, C1-6 alkyl, C1-6 alkoxy, C2-6 alkoxyalkyl, a halogen atom, nitro, amino, trihalomethyl, cyano, or hydroxy;
D represents a single bond, C1-6 alkylene, C2-6 alkenylene, or C1-6 oxyalkylene;
in -G-R6,
1) G represents a single bond, C1-6 alkylene which may be substituted with 1 to 2 oxygen atom(s) and/or sulfur atom(s), C2-6 alkenylene which may be substituted with 1 to 2 oxygen atom(s) and/or sulfur atom(s), in which the alkylene and the alkenylene may be substituted with hydroxy or C1-4 alkoxy, xe2x80x94C(O)NHxe2x80x94, xe2x80x94NHC(O)xe2x80x94, xe2x80x94SO2NHxe2x80x94, xe2x80x94NHSO2xe2x80x94, or diazo;
R6 represents a C3-15 saturated or unsaturated carbocyclic ring, or a 4- to 15-membered heterocyclic ring containing 1 to 5 nitrogen atom(s), sulfur atom(s) and/or oxygen atom(s), in which the ring may be substituted with 1 to 5 substituent(s) selected from C1-6 alkyl, C1-10 alkoxy, C2-6 alkoxyalkyl, a halogen atom, hydroxy, trihalomethyl, nitro, amino, phenyl, phenoxy, oxo, C2-6 acyl, C1-6 alkanesulfonyl and cyano,
2) G and R6 are taken together to represent
(i) C1-15 alkyl which may be substituted with 1 to 5 oxygen atom(s) and/or sulfur atom(s);
(ii) C2-15 alkenyl which may be substituted with 1 to 5 oxygen atom(s) and/or sulfur atom(s); or
(iii) C2-15 alkynyl which may be substituted with 1 to 5 oxygen atom(s) and/or sulfur atom(s),
in which the alkyl, the alkenyl and the alkynyl may be substituted with 1 to 12 substituent(s) selected from C1-6 alkoxy, a halogen atom, hydroxy, cyano, oxo and NR11R12, in which R11 and R12 each independently represents a hydrogen atom, C1-6 alkyl, C2-6 alkenyl, phenyl, benzoyl, naphthyl, phenyl substituted with C1-6 alkyl, or C1-6 alkyl substituted with phenyl or cyano;
n represents 1 to 3;
m represents 1 to 3;
i represents 1 to 4; and
 represents a single bond or a double bond, or a non-toxic salt thereof;
(2) a process for the preparation thereof;
(3) a pharmaceutical agent comprising it as an active ingredient; and
(4) 2-methylindole-4-acetic acid which is a novel synthetic intermediate.
In formula (I), the C1-6 alkyl represented by R2, R3, R4, R5, R6, R8, R9, R11, R12 or R13 includes, methyl, ethyl, propyl, butyl, pentyl, hexyl, and isomers thereof.
In formula (I), the C1-6 alkoxy represented by R1, R2, R3, R4 or R5 includes methoxy, ethoxy, propyloxy, butyloxy, pentyloxy, hexyloxy, and isomers thereof.
In formula (I), the C1-10 alkoxy represented by R6 includes methoxy, ethoxy, propyloxy, butyloxy, pentyloxy, hexyloxy, heptyloxy, octyloxy, nonyloxy, decyloxy, and isomers thereof.
In formula (I), the C1-15 alkyl represented by G and R6 taken together includes methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl, dodecyl, tridecyl, tetradecyl, pentadecyl, and isomers thereof.
In formula (I), the C1-15 alkyl which may be substituted with 1 to 5 oxygen atom(s) and/or sulfur atom(s) represented by G and R6 taken together represents the above alkyl in which any 1 to 5 carbon atom(s) are substituted with an oxygen atom(s) and/or a sulfur atom(s).
In formula (I), the C2-15 alkenyl represented by G and R6 which are taken together includes vinyl, propenyl, butenyl, pentenyl, hexenyl, heptenyl, octenyl, nonenyl, decenyl, undecenyl, dodecenyl, tridecenyl, tetradecenyl, pehtadecenyl, and isomers thereof.
In formula (I), the C2-15 alkenyl which may be substituted with 1 to 5 oxygen atom(s) and/or sulfur atom(s) represented by G and R6 which are taken together represents the above alkenyl in which any 1 to 5 carbon atom(s) are substituted with an oxygen atom(s) and/or a sulfur atom(s).
In formula (I), the C2-15 alkynyl represented by G and R6 which are taken together includes ethynyl, propynyl, butynyl, pentynyl, hexynyl, heptynyl, octynyl, nonynyl, decynyl, undecynyl, dodecynyl, tridecynyl, tetradecynyl, pentadecynyl, and isomers thereof.
In formula (I), the C2-15 alkynyl which may be substituted with 1 to 5 oxygen atom(s) and/or sulfur atom(s) represented by G and R6 which are taken together represents the above alkynyl in which any 1 to 5 carbon atom(s) are substituted with an oxygen atom(s) and/or a sulfur atom(s).
In formula (I), the C2-6 alkoxyalkyl represented by R2, R4, R5 or R6 includes methoxymethyl, methoxyethyl, methoxypropyl, methoxybutyl, methoxypentyl, ethoxymethyl, ethoxyethyl, ethoxypropyl, ethoxybutyl, propyloxymethyl, propyloxyethyl, propyloxypropyl, butyloxymethyl, butyloxyethyl, pentyloxymethyl, and isomers thereof.
In formula (I), the C1-6 alkylene represented by D or G includes methylene, ethylene, trimethylene, tetramethylene, pentamethylene, hexamethylene, and isomers thereof.
In formula (I), the C2-6 alkenylene represented by D includes vinylene, propenylene, butenylene, pentenylene, hexenylene, and isomers thereof.
In formula (I), the C1-6 oxyalkylene represented by D includes oxymethylene, oxyethylene, oxybutylene, oxypehtylene, oxyhexylene, and isomers thereof.
In formula (I), the C1-6 alkylene which may by substituted with 1 to 2 oxygen atom(s) and/or sulfur atom(s) represented by G includes the above C1-6 alkylene in which any carbon atom(s) is/are substituted with an oxygen atom(s) and/or a sulfur atom(s).
In formula (I), the C2-6 alkenylene which may by substituted with 1 to 2 oxygen atom(s) and/or sulfur atom(s) represented by G includes the above C2-6 alkenylene in which any saturated carbon atom(s) is/are substituted with an oxygen atom(s) and/or a sulfur atom(s).
In formula (I), the C2-6 alkenyl represented by R11 or R12 includes vinyl, propenyl, butenyl, pentenyl, hexenyl, and isomers thereof.
In formula (I), the halogen atom represented by R2, R3, R4, R5 or R6 includes fluorine, chlorine, bromine, and iodine.
In formula (I), the trihalomethyl represented by R2, R3, R4, R5 or R6 includes trifluoromethyl, trichloromethyl, tribromomethyl, and triiodomethyl.
In formula (I), the C1-10 alkoxy represented by R10 includes methoxy, ethoxy, propyloxy, butyloxy, pentyloxy, hexyloxy, heptyloxy, octyloxy, nonyloxy, decyloxy, and isomers thereof.
In formula (I), the C2-6 acyl represented by R6 includes acetyl, propionyl, butyly, valeryl, hexanoyl, and isomers thereof.
In formula (I), the C1-6 alkanesulfonyl represented by R6 includes methanesulfonyl, ethanesulfonyl, propanesulfonyl, butanesulfonyl, pentanesulfonyl, hexanesulfonyl, and isomers thereof.
In formula (I), the C3-15 carbocyclic ring represented by R6 or R13 includes monocyclic, bicyclic or tricyclic unsaturated or saturated carbocyclic ring having carbon numbers of 3 to 15.
Examples of the monocyclic, bicyclic or tricyclic unsaturated or saturated carbocyclic ring having carbon numbers of 3 to 15 include cyclopropane, cyclobutane, cyclopentane, cyclohexane, cycloheptane, cyclooctane, cyclopentene, cyclohexene, cyclopentadiene, cyclohexadiene, benzene, pentalene, indene, naphthalene, azulene, perhydropentalene, perhydroindene, dihydronaphthalene, tetrahydronaphthalene, perhydronaphthalene, perhydroazulene, heptalene, biphenylene, fluorene, phenanthrene, anthracene, dihydroanthracene, tetrahydroanthracene, perhydroanthracene, fluorene, dihydrofluorene, tetrahydrofluorene, perhydrofluorene, norbornane, norpinane, norbornane, norbornene, norpinane, norpinene rings and the like.
In formula (I), the 4- to 15-membered heterocyclic ring containing 1 to 5 nitrogen atom(s), sulfur atom(s) and/or oxygen atom(s) represented by R6 or R13 is unsaturated or saturated, and examples includes the following formulas:
In formula (I), R1 is preferably hydroxy, C1-6 alkyl or NR8R9, and more preferably hydroxy or C1-8 alkyl.
In formula (I), R2 is preferably a hydrogen atom, C1-6 alkyl or C1-6 alkoxyalkyl, and more preferably a hydrogen atom, C1-2 alkyl or C1-2 alkoxyalkyl.
In formula (I), R3 is preferably a hydrogen atom or C1-6 alkyl.
In formula (I), R4 is preferably a hydrogen atom or C1-6 alkyl, and more preferably a hydrogen atom or C1-2 alkyl.
In formula (I), R5 is preferably a hydrogen atom or C1-6 alkyl, and more preferably a hydrogen atom or C1-2 alkyl.
In formula (I), D is preferably a single bond or C1-6 alkylene, and more preferably a single bond or C1-2 alkylene.
In formula (I), G is preferably C1-6 alkylene which may be substituted with 1 or 2 oxygen atom(s), and more preferably C1-2 alkylene which may be substituted with one oxygen atom.
In formula (I), R6 is preferably a C5-10 carbocyclic ring or a monocyclic or bicyclic 5- to 10-membered heterocyclic ring containing 1 to 3 nitrogen, oxygen and/or sulfur atom(s), which each may be substituted, and more preferably a bicyclic 9- or 10-membered heterocyclic ring containing 1 to 3 nitrogen, oxygen and/or sulfur atoms(s) which may be substituted.
Also, G and R6 are preferably taken together to represent C1-10 alkyl which may be substituted with 1 to 4 oxygen and/or sulfur atom(s), C2-10 alkenyl which may be substituted with 1 to 4 oxygen and/or sulfur atom(s), or C2-10 alkynyl which may be substituted with 1 to 4 oxygen and/or sulfur atom(s).
Unless otherwise indicated, all isomers are included in the present invention. For example, the alkyl, alkenyl and alkynyl groups and alkylene group include straight-chain groups and branched-chain groups. In addition, isomers in double bond, ring, fused ring (E-, Z-, cis-, trans-isomer), isomers generated from asymmetric carbon atom(s) (R-, S-, xcex1-, xcex2-isomer, enantiomer, diastereomer), optically active isomers having optical rotation (D-, L-, d-, I-isomer), polar compounds separated by chromatography (high polar compound, low polar compound), equilibrium compounds, mixtures thereof at arbitrary ratios and racemic mixtures are included in the present invention.
Among the compounds of the present invention represented by formula (I), preferred compounds are compounds shown in Examples, compounds represented by formula (I-A1):
(wherein when R6 represents a ring, R61 represents a substituent of the ring; p is 0 or an integer of 1 to 3; and other symbols have the same meanings as described above), formula (I-A2):
(wherein all symbols have the same meanings as described above), formula (I-A3):
(wherein all symbols have the same meanings as described above), formula (I-A4):
(wherein all symbols have the same meanings as described above), formula (I-A5):
(wherein all symbols have the same meanings as described above), formula (I-A6):
(wherein all symbols have the same meanings as described above), formula (I-A7):
(wherein all symbols have the same meanings as described above), formula (I-A8):
(wherein all symbols have the same meanings as described above), formula (I-A9):
(wherein all symbols have the same meanings as described above), formula (I-A10):
(wherein all symbols have the same meanings as described above), formula (I-B1)1
(wherein all symbols have the same meanings as described above), formula (I-B2):
(wherein all symbols have the same meanings as described above), formula (I-B3):
(wherein all symbols have the same meanings as described above), formula (I-B4):
(wherein all symbols have the same meanings as described above), formula (I-B5):
(wherein all symbols have the same meanings as described above), formula (I-B6):
(wherein all symbols have the same meanings as described above), formula (I-B7):
(wherein all symbols have the same meanings as described above), formula (I-B8):
(wherein all symbols have the same meanings as described above), formula (I-C1):
(wherein all symbols have the same meanings as described above), formula (I-C2):
(wherein all symbols have the same meanings as described above), formula (I-C3):
(wherein all symbols have the same meanings as described above), formula (I-C4):
(wherein all symbols have the same meanings as described above), formula (I-C5):
(wherein all symbols have the same meanings as described above), formula (I-C6):
(wherein all symbols have the same meanings as described above), formula (I-C7):
(wherein all symbols have the same meanings as described above), formula
(wherein all symbols have the same meanings as described above), formula (I-C9):
(wherein all symbols have the same meanings as described above), formula (I-C10):
(wherein all symbols have the same meanings as described above), formula (I-C11):
(wherein all symbols have the same meanings as described above), formula (I-C12)
(wherein all symbols have the same meanings as described above), formula (I-C13)
(wherein all symbols have the same meanings as described above), formula (I-C14)
(wherein all symbols have the same meanings as described above), formula (I-C15):
(wherein all symbols have the same meanings as described above), formula (I-D1):
(wherein all symbols have the same meanings as described above), formula (I-D2):
(wherein all symbols have the same meanings as described above), formula (I-D3):
(wherein all symbols have the same meanings as described above), formula (I-D4):
(wherein all symbols have the same meanings as described above), formula (I-D5):
(wherein all symbols have the same meanings as described above), formula (I-D6):
(wherein all symbols have the same meanings as described above), formula (I-D7):
(wherein all symbols have the same meanings as described above), formula (I-D8):
(wherein all symbols have the same meanings as described above), formula (I-D9):
(wherein all symbols have the same meanings as described above), formula (I-E1):
(wherein all symbols have the same meanings as described above), formula (I-E2):
(wherein all symbols have the same meanings as described above), formula (I-E3):
(wherein all symbols have the same meanings as described above), formula (I-E4):
(wherein all symbols have the same meanings as described above), formula (I-E5):
(wherein all symbols have the same meanings as described above), formula (I-E6):
(wherein all symbols have the same meanings as described above), formula (I-E7):
(wherein all symbols have the same meanings as described above), formula (I-E8):
(wherein all symbols have the same meanings as described above), formula (I-E9):
(wherein all symbols have the same meanings as described above), formula (I-E10):
(wherein all symbols have the same meanings as described above), formula (I-E12):
(wherein all symbols have the same meanings as described above), formula (I-E12):
(wherein all symbols have the same meanings as described above), formula (I-E13):
(wherein all symbols have the same meanings as described above), formula (I-E14):
(wherein all symbols have the same meanings as described above), formula (I-E15):
(wherein all symbols have the same meanings as described above), formula (I-E16):
(wherein all symbols have the same meanings as described above), formula (I-E17):
(wherein all symbols have the same meanings as described above), formula (I-E18):
(wherein all symbols have the same meanings as described above), formula (I-E19):
(wherein all symbols have the same meanings as described above), formula (I-E20):
(wherein all symbols have the same meanings as described above), formula (I-E21)
(wherein all symbols have the same meanings as described above), formula (I-E22)
(wherein all symbols have the same meanings as described above), formula (I-E23):
(wherein all symbols have the same meanings as described above), formula (I-F1):
(wherein all symbols have the same meanings as described above), formula (I-F2):
(wherein all symbols have the same meanings as described above), formula (I-F3):
(wherein all symbols have the same meanings as described above), formula (I-F4):
(wherein all symbols have the same meanings as described above), formula (I-F5):
(wherein all symbols have the same meanings as described above), formula (I-F6):
(wherein all symbols have the same meanings as described above), formula (I-F7):
(wherein all symbols have the same meanings as described above), formula (I-F8):
(wherein all symbols have the same meanings as described above), formula (I-F9):
(wherein all symbols have the same meanings as described above), formula (I-F10):
(wherein all symbols have the same meanings as described above), formula (I-F11):
(wherein all symbols have the same meanings as described above), formula (I-F12):
(wherein all symbols have the same meanings as described above), formula (I-F13):
(wherein all symbols have the same meanings as described above), formula (I-F14):
(wherein all symbols have the same meanings as described above), compounds shown in Tables 1 to 5, and non-toxic salts of the compounds.
Salt:
The compound of the present invention represented by formula (I) can be converted into a corresponding salt by known methods. The salt is preferably a non-toxic and water-soluble salt. Appropriate salts include salts of alkali metals (potassium, sodium, etc.), salts of alkaline earth metals, ammonium salts (tetramethylammonium, tetrabutylammonium salts, etc.), and pharmaceutically acceptable organic amines (triethylamine, methylamine, dimethylamine, cyclopentylamine, benzylamine, phenethylamine, piperidine, monoethanolamine, diethanolamine, tris(hydroxymethyl)methylamine, lysine, arginine, N-methyl-D-glucamine, etc.).
The compound of the present invention represented by formula (I) and a salt thereof can also be converted into a hydrate by known methods.
Processes for the Preparation of the Compound of the Present Invention:
The compound of the present invention represented by formula (I) can be prepared by the following processes and the processes shown in Examples.
(a) Among the compounds represented by formula (I), a compound wherein R1 is hydroxy, i.e., a compound represented by formula (Ia):
(wherein all symbols have the same meanings as described above) can be prepared by subjecting to a deprotection reaction a compound represented by formula (IV):
(wherein R20 is an allyl or benzyl group; and other symbols have the same meanings as described above).
The deprotection reaction of ally ester or benzyl ester is known, for example, it is carried out in an organic solvent (e.g., methanol, ethanol, tetrahydrofuran, dioxane, ethyl acetate, etc.) at xe2x88x9210 to 90xc2x0 C. by
1) using tetrakis(triphenylphosphine)palladium and morpholine, or
2) using palladium carbon, palladium, platinum, sponge nickel (trade name: Raney Nickel), etc. under hydrogen atmosphere.
(b) Among the compounds represented by formula (I), a compound wherein R1 is C1-6 alkoxy (wherein all symbols have the same meanings as described above), i.e., a compound represented by formula (Ib):
(wherein R10 represents C1-6 alkyl; and other all symbols have the same meanings as described above) can be prepared by subjecting to an esterification reaction a compound represented by formula (Ia) with a compound represented by formula:
R10xe2x80x94OHxe2x80x83xe2x80x83(III)
(wherein all symbols have the same meanings as described above), followed by optionally a deprotection reaction.
The esterification reaction is known, for example, it is carried out in an inert organic solvent (tetrahydrofuran, methylene chloride, benzene, acetone, acetonitrile, a mixture thereof, etc.) in the presence or absence of a tertiary amine (dimethylaminopyridine, pyridine, triethylamine, etc.) using a condensing agent (1,3-dicyclohexylcarbodiimide (DCC), 1-ethyl-3-[3-(dimethylamino)propyl]carbodiimide (EDC), etc.) or acid halide (oxalyl chloride, thionyl chloride, phosphorus oxychloride, etc.) at 0 to 50xc2x0 C.
(c) Among the compounds represented by formula (I), a compound wherein R1 is xe2x80x94NR8R9 (wherein all symbols have the same meanings as described above), i.e., a compound represented by formula (Ic):
(wherein all symbols have the same meanings as described above) can be prepared by subjecting to an amidation reaction a compound represented by formula (Ia) with a compound represented by formula:
HNR10R11xe2x80x83xe2x80x83(II)
(wherein all symbols have the same meanings as described above), followed by optionally a deprotection reaction.
The amidation reaction is known, for example, it is carried out in an inert organic solvent (tetrahydrofuran, methylene chloride, benzene, acetone, acetonitrile, a mixture thereof, etc.) in the presence or absence of a tertiary amine (dimethylaminopyridine, pyridine, triethylamine, etc.) using a condensing agent (1,3-dicyclohexylcarbodiimide (DCC), 1-ethyl-3-[3-(dimethylamino)propyl]carbodiimide (EDC), etc.) or acid halide (oxalyl chloride, thionyl chloride, phosphorus oxychloride, etc.) at of 0 to 50xc2x0 C.
The compound represented by formula (IV) can prepared by subjecting to a compound represented by formula (V):
(wherein R21, R31 and R41 have the same meanings as R2, R3 and R4, respectively, and when they represent an amino group or a hydroxy group, they are protected with a protecting group; and other symbols have the same meanings as described above) with a compound represented by formula (VI):
(wherein R51 has the same meaning as R5, and when it represents an amino group or a hydroxy group, it is protected with a protecting group; and G1 and R61 have the same meanings as G and R6, respectively, and when they contains an amino group or a hydroxy group, it is protected with a protecting group), followed by optionally a deprotection reaction. The amidation reaction can be carried out by the above method.
The compounds represented by formula (II), (III), (V) and (VI) are known per se or can be prepared by known methods.
Among the compounds represented by formula (Ia), a compound wherein D is alkylene can be prepared by reducing a compound represented by formula (Ia), or can be prepared by increasing the carbon of the alkylene part.
In each reaction in the present specification, reaction products can be purified by conventional purification techniques, e.g., by distillation under atmospheric or reduced pressure, high performance liquid chromatography, thin layer chromatography or column chromatography using silica gel or magnesium silicate, washing, recrystallization or the like. Purification can be carried out after each reaction or after some reactions.
Pharmacological Activities:
The compound of the present invention represented by formula (I) potently binds to a DP receptor and show an antagonistic activity. For example, in a laboratory test, such effects were confirmed by the following receptor binding test using prostanoid receptor-expressing cells.
(i) Receptor Binding Test Using Prostanoid DP Receptor-Expressing Cells
CHO cells expressing a mouse DP receptor was prepared according to the method of Hirata et al. (Proc. Natl. Acad. Sci., 91, 11192-11196 (1994)) and used as a membrane standard.
A reaction solution (200 xcexcL) containing the prepared membrane standard (30-166 xcexcg) and 3H-PGD2 was incubated at room temperature for 20 minutes. The reaction was stopped with an ice-cold buffer (1 mL) and the binding 3H-PGD2 was trapped in on a glass filter by immediate aspiration-filtration under a reduced pressure, and its binding radioactivity was measured using a liquid scintillation counter.
A Kd value and a Bmax value were obtained from Scatchard plots (Ann. N.Y. Acad. Sci., 51, 660 (1949)). Non-specific binding was obtained as the binding radioactivity in the presence of unlabeled PGD2 at an excess amount (10 xcexcmol/L). 3H-PGD2 binding inhibition by the compound of the present invention was measured by adding 3H-PGD2 (2.5 mmol/L) and the compound of the present invention as various concentrations. Also, the following buffers were used for the reactions.
Incubation buffer:
HEPES-NaOH (25 mmol/L, pH 7.4)
EDTA (1 mmol/L)
MgCl2 (5 mmol/L)
MnCl2 (10 mmol/L)
Buffer for washing:
Tris-HCl (10 mmol/L, pH 7.5)
NaCl (0.1 mol/L)
Bovine serum albumin (0.01%)
The dissociation constant (Ki) (xcexcmol/L) of each compound was obtained by the following equation.
Ki=IC50/(1+([L]*/Kd))
[L*]: Concentration of radioligand
The results are shown in Table 6.
As shown in the above results, it is apparent that the compound of the present invention potently binds to a DP receptor.
(ii) DP Antagonistic Activity Assay Using Prostanoid DP Receptor-Expressing Cells
CHO cells expressing a mouse DP receptor were prepared according to the method of Nishigaki et al. (FEBS lett., 364, 339-341 (1995)), inoculated onto a 24-well microplate at 105 cells/well, followed by culturing for 2 days, and used for the assay. Each well was washed with 500 xcexcL of MEM (minimum essential medium), and 450 xcexcL of assay medium (MEM containing 1 mmol/L IBMX and 0.1 or 1% BSA), followed by incubation at 37xc2x0 C. for 10 minutes. Then, an assay medium (50 xcexcL) containing PGD2 alone or PGD2 with a test compound was added thereto to start the reaction, and after the reaction at 37xc2x0 C. for 10 minutes, 500 xcexcL of ice-cold trichloroacetatic acid (TCA) (10% w/v) was added thereto to stop the reaction. The reaction solution was frozen once (xe2x88x9280xc2x0 C.) and thawed, and cells were peeled using a scraper, followed by centrifugation at 13,000 rpm for 3 minutes. The cAMP concentration was measured with a cAMP assay kit using the resulting supernatant. That is, [125I]-cAMP assay kit buffer was added to 125 xcexcL of the supernatant to give a total amount of 500 xcexcL, and the resulting mixture was mixed with 1 mL of a chloroform solution of 0.5 mol/L tri-n-octylamine. Trichloro acetic acid (TCA) was extracted to the chloroform layer and removed, the cAMP amount in a sample was determined using the aqueous layer as the sample according to the method described in the [125I]cAMP assay kit.
Also, with regard to the antagonistic activity (IC50) of the test compound, the IC50 value was calculated as an inhibition rate based on the reaction at 100 nM which was a concentration showing submaximal cAMP production by PGD2 alone.
As shown in the above results, it is apparent that the compound of the present invention has an antagonistic activity against a DP receptor.
Toxicity:
The toxicity of the compound represented by formula (I) of the present invention is very low so that it is confirmed that the compound is sufficiently safe for using as a pharmaceutical.
Application to Pharmaceuticals:
Since the compound of the present invention represented by formula (I) bind to and is antagonistic to a DP receptor, it is considered that the compound is useful for the prevention and/or treatment of diseases, for example, allergic diseases such as allergic rhinitis, allergic conjunctivitis, atopic dermatitis, bronchial asthma, food allergy, etc.; systemic mastocytosis; disorders due to systemic mastocyte activation; anaphylactic shock; bronchoconstriction; urticaria; eczema; allergic bronchopulmonary aspergillosis; inflammatory paranasal sinus; nasal polyp; hypersensitive angitis; eosinophilia; contact dermatitis; diseases accompanied with itching, such as atopic dermatitis, urticaria, allergic conjunctivitis, allergic rhinitis, contact dermatitis, etc.; secondary diseases caused by behaviors (scratching behaviors, beating, etc.), such as cataract, retinal detachment, inflammation, infection, sleep disorder, etc.; inflammation; chronic obstructive pulmonary disease; ischemic reperfusion disorder; cerebrovascular disorder; pleuritis complicated by rheumatoid arthritis; ulcerative colitis; and the like. Moreover, the compound is considered to relate to sleeping and platelet aggregation and to be useful for these diseases.
Among the compounds of the present invention represented by formula (I), one having a weak binding activity to a compound other than a DP receptor would be used as a pharmaceutical having less side effects because it does not show other activity.
When the compound represented by formula (I) of the present invention, a non-toxic salt or a cyclodextrin inclusion compound thereof is normally administered systemically or topically and orally or parenterally.
The dosages are determined depending on age, body weight, symptom, therapeutic effect, administration route, duration of the treatment and the like. Generally, 1 xcexcg to 100 mg per adult is orally administered once to several times per day, or 0.1 xcexcg to 10 mg per adult is parenterally administered (preferably by intravenous administration) once to several times per day, or continuously administered from vein for 1 to 24 hours per day.
Since the dose changes depending on various conditions as described above, there are cases in which doses lower than or greater than the above ranges may be used.
The compounds of the present invention may be administered in the form of solid compositions, liquid compositions or other compositions for oral administration, and injections, liniments, suppositories and the like for parenteral administration.
Solid compositions for oral administration include compressed tablets, pills, capsules, dispersible powders, granules and the like.
Capsules include hard capsules and soft capsules.
In such solid compositions, one or more active compound(s) is/are mixed with at least one inert diluent such as lactose, mannitol, glucose, hydroxypropyl cellulose, microcrystalline cellulose, starch, polyvinyl pyrrolidone or magnesium metasilicate aluminate.
The compositions may also contain additional substances other than inert diluents, e.g., lubricating agents such as magnesium stearate, disintegrating agents such as cellulose calcium glycolate, and assisting agents for dissolving such as glutamic acid, asparatic acid according to usual methods. The tablets or pills may, if desired, be coated with film of gastric- or enteric-coating agents such as sugar, gelatin, hydroxypropyl cellulose or hydroxypropyl cellulose phthalate, or be coated with two or more films. Furthermore, capsules of absorbable materials such as gelatin are included
Liquid compositions for oral administration include pharmaceutically acceptable emulsions, solutions, syrups and elixirs. In such compositions, one or more active compound(s) is/are dissolved, suspended or emulsified in an inert diluent commonly used (e.g., purified water, ethanol). Furthermore, such liquid compositions may also contain wetting agents or suspending agents, emulsifying agents, sweetening agents, flavoring agents, perfuming agents, and preserving agents.
Other compositions for oral administration include sprays containing one or more active compound(s) which are prepared by known methods. Spray compositions may contain stabilizing agents such as sodium hydrogen sulfate, stabilizing agents to give isotonicity, isotonic solutions such as sodium chloride, sodium citrate or citric acid, other than inert diluents. The process for preparing the sprays are described in U.S. Pat. Nos. 2,868,691 and 3,095,355.
Injections for parenteral administration include sterile aqueous or non-aqueous solutions, suspensions and emulsions. Aqueous solutions or suspensions include, for example, distilled water for injection and a physiological salt solution. Non-aqueous solutions or suspensions include propylene glycol, polyethylene glycol, plant oil such as olive oil, alcohol such as ethanol, POLYSORBATE80 (registered trade mark), and the like.
Such compositions may contain additional diluents such as preserving agents, wetting agents, emulsifying agents, dispersing agents, stabilizing agents, assisting agents such as assistant agents for dissolving (e.g., glutamic acid, aspartic acid). They may be sterilized by filtration through a bacteria-retaining filter, or incorporation or irradiation of a sterilizing agent. They may also be manufactured in the form of sterile solid compositions which can be dissolved in sterile water or other sterile diluent for injection immediately before use.
Other compositions for parenteral administration include liquids for external use, endemic liniments, ointments, suppositories for intrarectal administration and pessaries for intravaginal administration containing one or more active compound(s) which can be prepared by known methods.
The following Reference Examples and examples illustrate the present invention, but do not limit the present invention.
In the following chemical formula, Tf represents a trifluoromethanesulfoxy group, Boc represents a t-butoxycarbonyl group, TMS represents a trimethylsilyl group, and Bn represents a benzyl group.
The solvents in the parentheses show the developing or eluting solvents and the ratios of the solvents used are by volume in chromatographic separations or TLC.
The solvents in the parentheses in NMR show the solvents for measurement.

Indole derivatives, process for preparation of the same and use thereof

Abstract: (wherein all symbols are described in the description), a process for the preparation of the same and a DP receptor antagonist comprising it as an active ingredient. Since the compounds of formula (I) binds to and are antagonistic to a DP receptor, they are useful in for the prevention and/or treatment of diseases, for example, allergic diseases (allergic rhinitis, allergic conjunctivitis, atopic dermatitis, bronchial asthma, food allergy, etc., systemic mastocytosis; disorders due to systemic mastocyte activation, anaphylactic shock, bronchoconstriction, urticaria, eczema, etc.), diseases accompanied with itching (atopic dermatitis, urticaria, etc.), secondary diseases caused by behaviors (scratching behaviors, beating, etc.) (cataract, retinal detachment, inflammation, infection, sleep disorder, etc.), inflammation, chronic obstructive pulmonary disease, ischemic reperfusion disorder, cerebrovascular disorder, pleuritis complicated by rheumatoid arthritis, ulcerative colitis, and the like.


In accordance with the aspects of the present invention, an improved container locking arrangement for a single piece blank and container is disclosed. The present invention includes a blank or a container including a bottom panel with first and second bottom sidewall panels, front and rear opposing wall panels, and first and second box corner locking constructions. Engagement of the corner locking constructions hingedly controls the relative position of the bottom sidewall panels. The corner locking constructions form first and second angled sidewall panels. Sidewall panel tabs disposed on an edge of the angled sidewall panels engage slots on the front wall panel to lock the first and second sidewall panels and the front wall panel in an assembled position. A top panel is hingedly configured to cover the bottom panel, thereby closing the container. First and second top panel flaps engage the first and second corner locking constructions to lock the top panel relative to the bottom panel.

The present invention relates to corrugated board containers, and more particularly to pizza style containers formed from a single piece blank.
Pizza style boxes are currently available in a wide variety of shapes and sizes. Many of the boxes include a square bottom panel, upright sidewalls, and a single lid panel that folds over the entire container. The sidewalls are typically formed as xe2x80x9crolloverxe2x80x9d walls that require a person to fold a first panel around a second panel and then secure the second panel into place.
Current container designs have a number of drawbacks. One disadvantage concerns the time to set up boxes. Many pizza establishments will use hundreds of pizza boxes at a single location during the dinner and evening hours. The boxes are often completely or partially set up ahead of time for use during these rush periods. Setting up a conventional pizza style box, however, takes time and labor, costs that must be accounted for in the price of the pizza. In addition, there is the difficulty encountered in forming and using these boxes, and particularly those with rolled sidewalls. Forming a rolled sidewall box can take more than an acceptable amount of time and can also place an employee at risk for xe2x80x9cCarpal Tunnel Syndromexe2x80x9d or similar disorder due to the wrist motion required to form the rolled walls. Similar drawbacks are found when pizza style boxes are used in other applications, such as holding coiled hose or wire.
Such pizza boxes also suffer from the tendency for the lid to fail to maintain a closed position. When a pizza box lid pops open, the pizza product inside can suffer heat loss, and, depending on the circumstances, the pizza may become inadvertently contaminated. In addition, the closure mechanisms used to engage the lid can interfere with the top of the pie, resulting in a gooey, unappetizing mess.
In accordance with the aspects of the present invention, an improved box corner locking construction for a single piece blank and container is disclosed. The present invention includes a blank or a container including a bottom panel with first and second bottom sidewall panels, front and rear opposing wall panels, and first and second box corner locking constructions. Engagement of the corner locking constructions hingedly controls the relative position of the bottom sidewall panels. The corner locking constructions form first and second angled sidewall panels, which engage the front wall panel to lock the first and second sidewall panels and the front wall panel in an assembled position. A top panel is hingedly configured to cover the bottom panel, thereby closing the container. First and second top panel flaps engage the first and second corner locking constructions to lock the top panel relative to the bottom panel and to further reinforce the front wall panel.


A wireless power supply device, which supplies electric power to a movable body by causing an end surface of a power supply coil that is provided in an electric power supply space to face a power receiving coil that is provided in the movable body, and by electromagnetically coupling the power supply coil with the power receiving coil, includes a position setting member configured to set the end surface of the power supply coil in a vertical position in a state of not detecting entry of the movable body into the electric power supply space, and to cause a position of the end surface of the power supply coil to change from the vertical position to a horizontal position upon detecting entry of the movable body into the electric power supply space.

Patent Document 1 discloses a wireless power supply system that prevents a foreign object from intruding into the space formed between an electric power receiving portion that is provided at the bottom surface of a vehicle and an electric power supply portion that is embedded in a parking space, and performs power supply safely and efficiently. The wireless power supply system, as shown in FIG. 1 and FIG. 2 of Patent Document 1, prevents the intrusion of a foreign object by covering with a separator material the space between the primary coil (power supply coil) that is embedded in the parking space (ground surface) and the secondary coil (power receiving coil) that is provided in the vehicle.


A tracking system and method in an optical communications system utilizing an optical communications beam. In one embodiment, the disclosed optical communications system includes a communications receiver circuit and a tracking circuit. The optical communications system generates a communications signal. The tracking system includes a tracking detector having a plurality of regions coupled to a corresponding plurality of tracking channel circuits. Each of the tracking channel circuits includes an optical detector coupled to receive the optical communications beam. The peak-to-peak amplitude modulation in the optical communications beam is measured by substantially reducing or removing a direct current (DC) offset present in the optical communications beam. In one embodiment, after the DC offset is substantially reduced or removed, the signal is then amplified, mixed with the communications signal and then filtered. The filtered signal is one of a plurality of tracking signal outputs, which are input to an alignment circuit. The alignment circuit is used to help maintain the alignment of the optical communications beam between the optical transmitter and receiver of the optical communications system. In one embodiment, each of the plurality of tracking signal outputs are also input into a gain control circuit. The gain control circuit is coupled to generate a gain control signal, which used to control the gain of variable gain amplifiers in the tracking channel circuits.

1. Field of the Invention
The present invention relates generally to wireless communications and, more specifically, the present invention relates to optical communications systems.
2. Background Information
With the increasing popularity of wide area networks (WANs), such as the Internet and/or the World Wide Web, network growth and traffic has exploded in recent years. Network users continue to demand faster networks and more access for both businesses and consumers. As network demands continue to increase, existing network infrastructures and technologies are reaching their limits.
An alternative to present day hardwired or fiber network solutions is the use of wireless optical communications. Wireless optical communications utilize point-to-point communications through free space and therefore do not require the routing of cables or fibers between locations. Thus, wireless optical communications are also known as free space or atmospheric optical communications. For instance, in a free space optical communication system, a beam of light is directed through free space from a transmitter at a first location to a receiver at a second location. Data or information is encoded into the beam of light, and therefore, the information is transmitted through free space from the first location to the second location.
An important aspect of a free space optical communications system is tracking. In particular, it is important that the optical communications beam (e.g. laser beam) is aimed properly from the transmitter at the first location and that the receiver at the second location is aligned properly to receive the optical communications beam. For example, assume that a transmitter is mounted on a first building and that a receiver is mounted on a different second building. Assume further that there is a line of sight between the transmitter and receiver. It is important for the transmitter on the first building to be configured to accurately direct or aim the optical communications beam at the receiver on the second building.
Tracking is utilized for maintaining the alignment of the optical communications beam between the transmitter and receiver in various situations or disturbances. Examples of these various situations or disturbances include the swaying of the buildings due to for example windy conditions, vibration of the platforms on which the transmitter and/or receiver are mounted, atmosphere-induced beam steering, etc. If the tracking system is unable to compensate for disturbances, the optical communications beam is no longer properly aimed at the receiver and, consequently, communications between the transmitter and receiver are lost or impaired.
An apparatus is disclosed in which an optical detector is optically coupled to receive an optical communications beam directed from optics. In one embodiment, an amplifier alternating current (AC) coupled to the optical detector. A mixer circuit is coupled to receive an output of the amplifier and a communications signal. The communications signal is generated by a communications receiver circuit in response to the optical communications beam. The mixer circuit coupled to generate a first single polarity output signal in response to an output of the amplifier and the communications signal to facilitate aligned reception of the optical communications beam by the optics. Additional features and benefits of the present invention will become apparent from the detailed description, figures and claims set forth below.

Method and apparatus for tracking an optical communications system


The invention relates to a method for performing a radio resource control (RRC) connection or reestablishment in a communication system using carrier aggregation (CA), and to a terminal device for same. The present invention involves acquiring information on an additional component carrier (CC) through system information in addition to the CC which is specified during cell selection or reselection, and enables the CC on which additional information is acquired to be usable during the RRC connection or reestablishment performed by user equipment, to thereby prevent loads from being concentrated on a specific CC.

Long Term Evolution (LTE) is an evolution of Universal Mobile Telecommunications System (UMTS), standardized by an international standardization body, 3rd Generation Partnership Project (3GPP). The configuration of an LTE system is illustrated in FIG. 1.
FIG. 1 is a view referred to for describing the configuration of an LTE system.
The LTE system may be divided largely into an Evolved UMTS Terrestrial Radio Access Network (E-UTRAN) and an Evolved Packet Core (EPC). The E-UTRAN includes UEs and evolved Node Bs (eNBs). A UE is connected to an eNB via a Uu interface and one eNB is connected to another eNB via an X2 interface. The EPC includes a Mobility Management Entity (MME) responsible for control-plane (C-plane) functions and a Serving GateWay (S-GW) responsible for user-plane (U-plane) functions. An eNB is connected to the MME via an S1-MME interface and an eNB is connected to the S-GW via an S1-U interface. These two interfaces are collectively called an S1 interface.
For the Uu interface being an air interface, a radio interface protocol stack is defined. The radio interface protocol stack horizontally includes a PHYsical (PHY) layer, a data link layer, and a network layer and vertically includes a U-plane for user data transmission and a C-plane for control signaling. Based on the lowest three layers of the Open System Interconnection (OSI) reference model known in communication systems, this radio protocol stack can be divided into Layer 1 (L1) including a PHY layer, Layer 2 (L2) including a Medium Access Control/Radio Link Control/Packet Data Convergence Protocol (MAC/RLC/PDCP) layer, and Layer 3 (L3) including a Radio Resource Control (RRC) layer. These layers are defined in pairs between a UE and an Evolved UTRAN (E-UTRAN), for data transmission via the Uu interface.
Now a description will be given below of a Long Term Evolution Advanced (LTE-A) system.
LTE-A is a system developed from LTE to meet the 4th Generation (4G) mobile communication requirements, that is, IMT-Advanced requirements recommended by the International Telecommunication Union-Radio communication sector (ITU-R). The 3GPP which developed the LTE system standard is now actively working on standardization of the LTE-A system.
Major technologies added to the LTE-A system are carrier aggregation for extending a used bandwidth and flexibly using the bandwidth and use of relays for supporting group mobility and enabling user-centered network deployment.
FIGS. 2 and 3 are views referred to for describing radio protocol layers.
At L1, the PHY layer provides information transfer service to its higher layer on physical channels. The PHY layer is connected to the MAC layer through transport channels and data is transferred between the MAC layer and the PHY layer on the transport channels. The transport channels are largely divided into dedicated transport channels and common transport channels depending on whether the transport channels are shared or not. Data is transmitted on physical channels using radio resources between different PHY layers, that is, the PHY layers of a transmitter and a receiver.
There are a plurality of layers at L2. The MAC layer maps logical channels to transport channels and performs logical channel multiplexing by mapping a plurality of logical channels to one transport channel. The MAC layer is connected to its higher layer, the RLC layer through logical channels. Depending on the types of information carried on the logical channels, the logical channels are classified into control channels that deliver C-plane information and traffic channels that deliver U-plane information.
The RLC layer at L2 adjusts a data size to be suitable for data transmission in the air interface from a lower layer by segmenting and concatenating data received from a higher layer. In order to guarantee various Quality of Service (QoS) requirements of each Radio Bearer (RB), the RLC layer provides three operation modes, Transparent Mode (TM), Unacknowledged Mode (UM), and Acknowledged Mode (AM). Especially, an AM RLC performs a retransmission function through ARQ, for reliable data transmission.
The PDCP layer at L2 compresses a header to reduce the size of an Internet Protocol (IP) packet header of a relatively large size containing unnecessary control information to efficiently transmit an IP packet such as an IPv4 or IPv6 packet via a radio link having a narrow bandwidth. The header compression function enables transmission of necessary information in a header only, thereby increasing the transmission efficiency of a radio link. In addition, the PDCH layer performs a security function in the LTE system. This security function involves ciphering for preventing a third part from eavesdropping and integrity protection for preventing a third party from maliciously modifying data.
The RRC layer at the highest of L3 is defined only on the C-plane. The RRC layer takes charge of controlling logical channels, transport channels, and physical channels in relation to configuration, reconfiguration, and release of RBs. An RB is a logical path provided by L1 and L2 in the radio protocol architecture, for data transmission between a UE and a UTRAN. In general, configuring an RB means defining the features of a radio protocol layer and channels needed to provide a specific service and setting specific parameters and an operation scheme. RBs are classified into Signaling RB (SRB) and Data RB (DRB). The SRB is used as a path in which an RRC message is transmitted on the C-plane and the DRB is used as a path in which user data is transmitted on the U-plane.
Now, a description will be given of RRC_IDLE state of a UE. In the RRC_IDLE state, the UE should always select a cell having a suitable quality and prepare for receiving a service from the selected sell. For example, upon power-on, the UE should select a cell having a suitable quality to register to a network. If the UE transitions from RRC_CONNECTED to the RRC_IDLE state, it should select a cell to camp on. The process of selecting a cell satisfying a specific condition to stay in a service idle state such as the RRC_IDLE state is called cell selection.
How a UE selects a cell will be described in detail. Upon initial power-on, the UE searches available Public Land Mobile Networks (PLMNs) and selects a suitable PLMN from which to receive a service. Subsequently, the UE selects a cell having a signal quality and characteristics good enough to provide a service to the UE. Cell selection is largely divided into two processes. One is initial cell selection. During initial cell selection, the UE has no prior knowledge of radio channels. Therefore, the UE scans all radio channels to search for a suitable cell. Once the UE detects a suitable cell satisfying a cell selection criterion, it selects the detected cell. The other cell selection process is cell selection. During cell selection, the UE selects a cell based on stored information about radio channels or information broadcast from cells. Accordingly, cell selection can be faster than during initial cell selection. Once the UE detects a cell satisfying the cell selection criterion, it selects the detected cell. If the UE fails to detect a suitable cell satisfying the cell selection criterion, it performs initial cell selection.
How a UE reselects a cell will be described below. After the UE selects a cell through cell selection, signal strength or quality between the UE and an eNB may change due to a change in the mobility of the UE or a change in radio environment. If the quality of the selected cell is degraded, the UE may select another cell offering a better quality. When reselecting a cell in this manner, the UE generally selects a cell having a better signal quality than the current cell. This process is called cell reselection. The basic purpose of cell reselection lies in selection of a cell having the best quality. Aside from the aspect of radio signal quality, the network may prioritize frequencies and notify the UE of the priority levels of the frequencies. Then, the UE puts the priority levels of frequencies before the qualities of radio signals during cell reselection.
Now a description will be given of CA in the LTE-A system.
FIG. 4 is a view referred to for describing CA.
As described above, the LTE-A standard is designed as an IMT-Advanced candidate technology of the ITU to satisfy IMT-Advanced technical requirements. Accordingly, extension of a bandwidth from the legacy LTE system is under discussion to satisfy IMT-Advanced technical requirements. For bandwidth extension, carriers available to the legacy LTE system are defined as Component Carriers (CCs) in the LTE-A system. Aggregation of up to 5 CCs is under discussion, as illustrated in FIG. 4. Because a CC may occupy up to 20 MHz as in the LTE system, the CA technology of the LTE-A standard is a concept of extending a bandwidth to up to 100 MHz. The technology of aggregating a plurality of CCs is called CA.

Method for performing RRC connection or reestablishment in a communication system using carrier aggregation


A corrugated produce container is formed from a single piece of suitably cut and scored corrugated packaging material. The container has a bottom, two side walls and multi-ply end panels. Suitable stacking tabs may be provided and the top closure panels can be folded over the stacking tabs. Hinged to each wide end panel is a multi-part reinforcing end panel having a first portion extending in the vertical direction and having a top member hinged thereto which is folded over and has one edge thereof sized to overlie the top edge of the end panel. Hinged to this portion is another vertically extending reinforcement member and hinged on the opposite side of it is the major reinforcement end panel. Suitable hand holds and ventilation apertures can also be provided.

The present invention relates generally to produce shipping containers and more particularly to single piece corrugated shipping containers having multi-ply end panels and a particular improvement for strength and stacking enhancement purposes. There are many single piece cut and scored paperboard blands useful for erecting into produce containers. One of the problems with the known prior art containers is their stacking strength and stability. The present invention attempts to overcome such problems with improved results.
Per the foregoing, one object of the present invention is to provide a single piece corrugated produce container which has enhanced stacking strength when a plurality of containers are stacked atop one another.
Another objects is to provide such improved strength with a minimal amount of additional material.
These and other objects will become apparent upon reading the specification to follow in conjunction with the attached drawings.


A linear guidance device has an elongated guiding rail having at least one throughgoing opening extending from the upper surface for receiving a mounting element for mounting the guiding rail on a lower component. A guidance car is displaceably guided on the guiding rail in a longitudinal direction of the guiding rail. A cover band can be attached to an upper surface of the guiding rail, the cover band formed so that a limiting line of a free end of the cover band is formed so that when a point of the cover band coincides with a boundary line of the throughgoing opening in a selected direction, a portion of the limiting line is arranged completely outside of a boundary line of the throughgoing opening.

The present invention relates to linear guiding devices. More particularly, it relates to a linear guidance device which has an elongated guiding rail with an upper surface and at least one throughoing opening extending from the upper surface for receiving a mounting element for mounting the guiding rail on a higher order unit, a guidance car displaceably guided on the guiding rail in its longitudinal direction, and a cover band attachable to the upper surface of the guiding rail and covering the at least one throughgoing opening.
Such a linear guiding device in which the throughgoing openings for receiving the mounting elements for the guiding rail is covered with a cover band is disclosed for example in the German patent document DE 43 11 641 C1. Occasionally it happens that in such a linear guidance device, the cover band must be applied on the guiding rail in the condition in which the guidance car is already located on the guiding rail. In this case the cover band can not be clamped on the guiding rail, but instead must be displaced on the guiding rail from its end side. It is to be understood that during passage through the region covered by the guidance car, the seal which seals the guiding rail against the guiding rail must not be damaged. The cover band therefore must be placed as flat as possible on the guiding rail. It has been shown in practice that because of this flat placement, the outwardly extending free end of the cover band may come into engagement with and can be locked in the throughgoing openings for receiving the mounting elements of the guiding rail.


A method for treating hyperopia or presbyopia in a patient, the method comprising making a cut deep in the patient's cornea to create a two-dimensional slit adjacent to and generally parallel to an anterior surface of the cornea and injecting a liquid or semi-solid transparent filler material into the deep cut in an amount sufficient to flatten the posterior surface of the cornea to increase the refractive power of the cornea by a predetermined correction of up to about 5 diopters due to the physical flattening of the posterior surface of the cornea, wherein the transparent filler material comprises a refractive index of about 1.3 to about 1.6, and forms a corneal implant with a lenticular shape within the cornea.

Ametropia refers to significant refractive errors of the eye. Light is focused onto the retina mainly through a combination of refraction by the cornea-air interface, and through the ocular lens. Accommodation (adjusting the eye's focus) occurs through changes in the lens, which fine-tune the refractive power of the eye. Approximately 42 diopters (dpt) of the total refractive power of about 60 dpt of the eye is due to the curvature of the cornea, which does not change during accommodation. Ametropia includes myopia (near-sightedness), hyperopia (farsightedness), and astigmatism (cylindrical and other aberrations). All forms of ametropia can be corrected at least partially, by glasses or contact lenses.
Surgical corrections vary with the kind of ametropia. Most people with ametropia have myopia, which is surgically corrected by reducing the curvature of the cornea. Laser-Assisted in situ Keratomileusis (LASIK), photorefractive keratotomy (PRK), and similar techniques remove a thin lenticular layer of tissue from within the stroma of the central cornea, reducing its outer curvature. LASIK is by far the most frequently used technique. A laminar cut is made in the stroma using a microtome or a short pulsed laser, which creates a thin flap that remains attached at one edge. When a laser is used to create the flap, cutting is carried out by a scanning laser focused within the corneal stroma, followed by a ring-shaped cut through the outer surface of the cornea. The opened flap exposes the cornea stroma. An excimer laser is then used to remove a precise, lenticular-shaped, thin layer of cornea tissue, followed by closing the flap, which re-attaches by adhesion. The pattern and amount of tissue removed is precisely determined to produce the desired reduction in cornea curvature. Astigmatism can also be corrected by LASIK.
Novel, but not yet approved refractive procedures like ReLEx® (Refractive LEnticule Extraction), e.g., femtosecond lamellar extraction (FLEx), and SMILE (SMall Incision Lenticule Extraction) remove stromal lenticule by using femtosecond laser surgery, which is able to make precise cuts within the cornea without damage to the surface of the cornea. Radial keratotomy and similar techniques that injure the cornea in a peripheral pattern, reducing the central cornea curvature after healing, are highly invasive and not predictable enough and therefore not currently employed. For hyperopia correction, LASIK, radial keratotomy and similar techniques either do not work well, or at all.
To correct hyperopia, it is known that the curvature of the surface of the cornea must be increased. A variety of corneal rings have been devised to treat hyperopia. The early corneal rings were made from sutures, which acted like a purse string around the central cornea. An annular cut is made into the cornea around its central axis, and the ring is embedded into the stroma. By tightening or otherwise adjusting the ring, tension is partially relieved on the central cornea, causing its curvature to increase. Unfortunately, corneal rings are problematic compared with LASIK. A substantial injury is produced, the ring typically requires multiple adjustments, tension is concentrated at the ring itself, the degree of correction is difficult to predict, and it is difficult to correct astigmatism. Corneal rings pose so many problems that most patients with hyperopia elect not to use them.

Corneal fillers for correction of ametropia


A device for driving the lifting movement of an examination bed includes a horizontal support frame and a base support component that is pivotally connected to a swing arm component. The device includes a swing bar component including a swing bar. A first end of the swing bar is connected to a lifting movement element, and a second end of the swing bar is connected to a set position of the swing arm component. The device includes a sliding component including a linear guide element and at least one sliding element slidable relative to the linear guide element. The device also includes a swing arm component including at least one swing arm, with the first end of each of the swing arms being connected to the base support component and the second end of each of the swing arms being connected to the sliding element.

In Magnetic Resonance Imaging (MRI) equipment, computerized tomography (CT) equipment and other medical equipment, the examination bed for bearing patients may use lifting movement so as to move the patient to an effective diagnosis height and into an effective diagnosis area by a horizontal feeding mechanism for diagnosis.
FIG. 1 shows a lead screw nut type driving device for an MRI equipment hospital bed in the prior art. As shown in FIG. 1, the lead screw nut type driving device is located outside an examination bed 20. During the use, a motor 60 drives a lead screw 50 to rotate using a belt, so that a lead screw nut 40 sleeved on the lead screw 50 moves upward or downward, while the lead screw nut 40 is fixedly connected to the examination bed 20 via a vertical support component 30. The lead screw nut type driving device may drive the examination bed 20 to make the lifting movement. As a result, the examination bed 20 may be moved to the effective diagnosis height and further moved into the effective diagnosis area of a magnet 10 using a horizontal feed mechanism. The lead screw nut type driving device occupies a large space beside the hospital bed, so the operation of the operator is inconvenient. Due to such a horizontally placed installation structure, the lead screw suffers from significant horizontal stress and is in a super-position state. This brings a great deal of difficulty to the installation and also brings high cost.

Device for driving lifting movement of examination bed, examination bed, and medical equipment


A protective structure for protecting bottles, particularly wine bottles, comprises a first pair of elements (10) which are spaced apart horizontally. The elements have recesses (12, 14) in their upper surfaces for receiving bottles. There is a second pair of elements inverted with respect to the first pair and having recesses in their lower edges. The recesses of the second pair of elements register with the recesses of the first pair of elements so as to define circular bottle receiving openings. A ring of cushioning material lines each opening. The cushioning material is in the form of semi-circular strips, the strips of registering recesses forming a ring, or in the form of a complete ring. Each ring includes a web (24) which lies against the semi-circular faces (20, 22) of the recesses (12, 14) and flanges (26) which lie against the side faces of the elements (10).

The generally accepted way of packaging wine for transportation is to provide an outer box, often of corrugated board, and internal partitions for separating the bottles from one another. In the simplest form the partitions comprise a number of vertical, transverse and longitudinal elements which intersect one another to form a plurality of vertically elongate compartments. A bottle stands in each compartment which is bounded either by four intersecting boards or by a number of boards and the inner surface of the carton.
In more complex packaging the bottles lie horizontally in moulded trays which are shaped to cradle the bottles and prevent movement. Examples of this type of packaging are disclosed in the following specifications:—
U.S. Pat. No. 6,820,743HurleyFrench Specification 2,155,005PapeteriesU.S. Pat. No. 7,237,675O'MalleyFrench Specification 1,205,747BlanchU.S. Pat. No. 1,967,026GrayU.S. Pat. No. 1,960,279ReadUK Specification 870,704Blanch
It is also known to provide the internal surfaces of the walls of a rigid box, for example of wood, with blind slots for receiving and supporting the free end of the neck and also the base of the bottle. An example of this type of packaging is found in French specification 2 967 401.
In the form described in French specification 1,268,153 (Cucurull) the carton has hard, internal, vertical partitions with semi-circular recesses in their top edges. There are smaller recesses for supporting the bottle necks and larger recesses for the main cylindrical parts of the bottles.
The partitions is covered by a corrugated, resilient sheet which initially extends across the upwardly open mouths of the recesses. When a bottle neck or base is inserted into a recess from above, the sheet is pressed into the recess by the bottle base or bottle neck so that it forms a cushion between the bottle and the partition.
Parts of the sheet lie against the sides of the partition and edge zones are secured to the base of the carton in which the partition is used. End tabs of the sheet are secured to the internal surfaces of opposed walls of the carton.
Much labour is required to cut the flexible corrugated sheet to shape, secure it to the hard partition and then secure it to the carton's base and walls.
The partition is fixed in the carton and no adjustment along the carton is possible after the sheet has been secured to the carton.
In French Specification 684094 there is disclosed a pre-formed support which defines a row of upwardly open recesses for receiving the necks of the bottles. In one disclosed form the support is sinusoidal in section so that upwardly facing and downwardly facing recesses are formed.
U.S. Pat. No. 4,341,308 discloses supports which have alternating large and small recesses in the upper edges thereof for receiving a row of bottles which are in reversed positions with respect to one another.
Specification GB 11,119 of 1898 discloses a packing case in which horizontally extending upper and lower partitions are provided for supporting bottles which are positioned vertically and upside down and pass through holes in the partitions. The holes of the lower partition each have a lining therein. Each lining comprises a sleeve in the hole in the partition and a flange which lies against the top face of the partition. The bottles are supported by the linings. The weight of each bottle presses the flange of the lining on which it bears against the top face of the partition.
The liquid in bottles which are vertical and inverted exerts a greater pressure on the bottle's seal than it does if the bottle is upright or is lying horizontally. The greater pressure that is exerted increases the possibility of leakage occurring.
To avoid this problem the case of specification 11119 could be used with the bottles horizontal. However, in such circumstances the vibrations and shocks to which the case is inevitably exposed could shake the lining out of the holes in the partitions as there is only one flange. This has the result that there can then be direct contact between the bottle and the hard partition should the case subsequently be subjected to shocks or impacts.
The present invention provided an improvement to the protective packaging disclosed in the specifications discussed and in particular an improvement in the packing case of UK specification 11,119.

Protective packaging in which wine bottles can be transported


A synchronous circuit according to an embodiment of the present invention, comprising:

This application is based upon and claims the benefit of priority from prior Japanese Patent Application No. P2002-085117, filed on Mar. 26, 2002; the entire contents of which are incorporated herein by reference.
The present invention relates to a synchronous circuit generating a synchronous clock signal by using multi-phases clock signals.
FIG. 7 is a block diagram of a synchronous circuit of a phase picking system in the related art of the present invention. The conventional synchronous circuit comprises a clock generator 1, a clock selector 2, a phase comparator 3, a phase control circuit 4, a phase information storage circuit 6, a frequency divider 7 and a deserializer 8.
The clock generator 1 includes a PLL (Phase Locked Loop) or a DLL (Delay Locked Loop) and generates a plurality of clock signals differing in phase from each other, so-called multi-phases clock signals, based on a reference signal. The phase comparator 3 detects a phase difference between received serial data and a clock signal selected by the clock selector 2 and then outputs a phase difference signal.
The phase control circuit 4 controls an edge of the clock signal to so as to be positioned in the center of the data based on the phase difference signal detected by the phase comparator 3. The phase information storage circuit 6 stores a clock-selecting signal outputted from the phase control circuit 4, and the clock selector 2 selects a suitable phase clock signal from the multi-phases clock signals according to the clock-selecting signal in the phase information storage circuit 6. The frequency divider 7, which receives the clock signal selected by the clock selector 2, generates a divided clock signal having lower frequency than the selected clock signal and supplies the divided clock signal to the phase control circuit 4, the phase information storage circuit 6 and the deserializer 8. The deserializer 8 converts a received serial data of a high bit rate, which is synchronized with the selected clock signal, into the parallel data of a low bit rate, which is synchronized with the divided clock signal obtained by the frequency divider 7, and outputting the parallel data.
Specifically, in the conventional synchronous circuit, when there is a data transition of the received serial data, a phase difference between the serial data and the selected clock signal is detected, and a phase error of the selected clock signal is adjusted according to this detection result.
A synchronous circuit according to an embodiment of the present invention, comprising:
a clock selector configured to select a suitable phase clock signal from a plurality of clock signals differing in phase from each other in accordance with a clock-selecting signal;
a phase comparator configured to compare a phase of input data with that of the selected clock signal;
a phase control circuit configured to generate a phase control signal in accordance with the comparison result obtained by the phase comparator and to generate the clock-selecting signal in accordance with a offset control signal; and
a frequency offset control circuit configured to generate the offset control signal in accordance with the phase control signal.


A power switch disposed in a housing includes a contact breaker configured to connect and disconnect a low-voltage switchgear from a power source supplying the low-voltage switchgear, a triggering device configured to disconnect the low-voltage switchgear in an overload event, a current detection device, a control device, a first evaluation device configured to evaluate an accidental arc overcurrent, and a second evaluation device configured to evaluate the accidental arc overcurrent. The power switch is configured to be activated via an overcurrent signal generated by an arc monitoring system in response to the accidental arc overcurrent. The overcurrent signal is linked to the at least one triggering signal. The second evaluation has a threshold above a threshold of the first evaluation device. The triggering device is configured to be activated via a turn-off pulse when a signal from the current detection device is above the threshold of the second evaluation device.

The cutout capability and switch-off time of a power switch in the event of an overcurrent, a short-circuit or an accidental arc are dependent on various parameters. The switching-off process is composed of the triggering time, the inherent time and the switch-off time. The triggering time is the time from the occurrence of the variable causing the triggering to the initiation of the triggering process, for example the disengagement of a switch latch. This is followed by the inherent time of the switch, which depends on the dynamic processes of the moving and opening contacts of the switch. In the case of a switch for a relatively high power range (nominal current of up to 100 kA), switch-off times can be up to 50 to 65 msec. There are power switches which include electronic triggering means (for example, DE 19743997 A1) and allow the functional configuration of the protective conditions for a switchgear to be variably adjusted. However, the switch-off times are not altered by this electronic means.
The occurrence of an accidental arc in an electrical installation can cause serious damage to persons and/or to property; such injury and damage should be limited as much as possible if not ruled out. To avoid such damage there have been proposed various measures, of which the cut-off (the extinguishing) of the accidental arc in a time shorter than the switch-off time of the feed switch is the optimum solution. The detection of accidental arcs requires current transformers which have to be added to a switchgear installation. This takes up space and is expensive. Furthermore, additional means have to be installed to extinguish an accidental arc. The additional costs of accidental arc extinguishing means are not always financially justifiable.
A publication ("New Strategy to Counteract Arc Flash Hazards" in TANSMISSION & DISTRIBUTION CONF. and EXPOSITION: LATIN AMERICA, 2006, IEEE, pages 1-6; by Santos L. F. et al.) describes an arc monitoring system, which reacts to the occurrence of an accidental arc. The system is associated with one control means, for evaluating the accidental arc overcurrent. A turn-off pulse will be issued merely if the signal from the current detection means is above a preadjustable threshold.

Power switch for preventing accidental arcs


A method of checking and acknowledging reception of a message in a two-way radio communication system without causing a reduction in the efficiency of processing the message, a storage medium on which a reception checking and acknowledging program is stored for use in the two-way radio communication system, and a two-way radio communication system and a base station for use in the two-way radio communication system is provided. If message data transmitted by a terminal device is received by a base station via a relay station and an Internet network, the base station generates reception acknowledgment data and transmits it in such a manner that when downstream message data is transmitted toward a plurality of terminal devices, the above-described reception acknowledgment data is added to the downstream message data and the resultant data is transmitted to the plurality of terminal devices.

1. Field of the Invention
The present invention relates to a method of checking reception of a message and transmitting reception acknowledgment information associated with the received message in a two-way radio communication system in which a plurality of communication terminal devices transmit and receive information to and from each other, and also to a storage medium on which a reception acknowledgment transmission program is stored for use in such a two-way radio communication system. The present invention also relates to a two-way radio communication system and a base station for use in the two-way radio communication system.
2. Discussion of the Background
In most widely-used paging systems or similar systems, a large-zone downstream radio system is employed, in which a message is transmitted in only one direction from a caller's telephone to a recipient's receiving terminal device such as a pager unit. There is no practical two-way radio communication system that allows a caller and a recipient to send and receive a message to and from each other.
Recently, a paging system has been proposed in which a called device sends a message reception acknowledgment signal to a calling device. For example, in the technique disclosed in Japanese Unexamined Patent Publication No. 61-208931, when a user of a pager unit serving as a receiving terminal device receives a message from a caller, if the user of the pager unit presses a particular button of the pager unit, data indicating the status of the called pager is sent to the caller. Japanese Unexamined Patent Publication No. 3-38122 discloses a technique in which when a pager unit receives a calling signal, a beeping sound is generated to inform a called person (user of the pager unit) of arrival of a message and an acknowledgment signal is sent to a caller.
However, the conventional techniques of checking and acknowledging reception of a message are applicable only to a one-way radio communication system in which a message is sent in only one direction from a caller to a recipient, and the techniques cannot be typically employed in a two-way radio communication system in which a message is sent in both directions. Another problem of the conventional techniques of checking and acknowledging reception of a message is that when a base station receives a reception acknowledgment signal sent from a called device, the base station immediately transfers the received acknowledgment signal to a calling device and thus the base station often encounters congestion of various data, which brings about a reduction in processing efficiency in the transmission of messages to called devices.

Method of checking and acknowledging reception of data in a two-way radio communication system


A plurality of cooling passages extending in an axial direction are formed in a transition piece so as to be aligned in a circumferential direction and the axial direction. One or more downstream side passages are formed in a downstream side region (Rd) within one circumferential region. One or more upstream side passages are formed in an upstream side region Ru within the circumferential region. The total cross-sectional area per unit circumferential length of the one or more downstream side passages is larger than the total cross-sectional area per unit circumferential length of the one or more upstream side passages.

A combustor of a gas turbine includes: a transition piece that demarcates a flow path of combustion gas; and a fuel supply unit that supplies fuel and air into the transition piece. Fuel is combusted and combustion gas generated from fuel combustion flows in the transition piece. Therefore, an inner circumferential surface of the transition piece is exposed to extremely high-temperature combustion gas.
Therefore, a plurality of cooling passages are formed between an outer circumferential surface and inner circumferential surface of a combustion liner demarcating the flow path of combustion gas, in a combustor disclosed in the following Patent Document 1, for example. A cooling medium flows in the cooling passages.

Transition piece, combustor provided with same, and gas turbine provided with combustor