The invention relates to compounds of the general formula (I)

The present invention relates to novel compounds, to pharmaceutical compositions comprising the compounds, to processes for their preparation, as well as to the use of the compounds for the preparation of a medicament which particularly acts on the central nervous system.
Many diseases of the central nervous system are influenced by the adrenergic, the dopaminergic, and the serotonergic neurotransmitter systems. For example, serotonin has been implicated in a number of diseases and conditions which originate in the central nervous system. A number of pharmacological and genetic experiments involving receptors for serotonin strongly implicate the 5-HT2c receptor subtype in the regulation of food intake (Obes. Res. 1995, 3, Suppl. 4, 449S-462S). The 5-HT2c receptor subtype is transcribed and expressed in hypothalamic structures associated with appetite regulation. It has been demonstrated that the 5-HT2c receptor agonist m-chlorophenylpiperazine (mCPP), which has some preference for the 5-HT2c receptor, reduces food intake in mice that express the normal 5-HT2c receptor while the compound lacks activity in mice expressing the mutated inactive form of the 5-HT2c receptor (Nature 1995, 374, 542-546). In a recent clinical study, a slight but sustained reduction in body weight was obtained after 2 weeks of treatment with mCPP in obese subjects (Psychopharmacology 1997, 133, 309-312). Recently, a series of pyrrolo[3,2,1-ij]quinoline derivatives was identified to be 5-HT2C receptor agonists having selectivity over the 5-HT2A receptor (Isaac M., et al., Bioorg. Med. Chem. Lett. 2000, 10, 919-921). The compounds are said to offer a novel approach to the treatment of obesity and epilepsy.
Weight reduction has also been reported from clinical studies with other xe2x80x9cserotonergicxe2x80x9d agents (see, e.g., IDrugs 1998, 1, 456-470). For example, the 5-HT reuptake inhibitor fluoxetine and the 5-HT releasing agent/reuptake inhibitor dexfenflurarnine have exhibited weight reduction in controlled studies. However, currently available drugs that increase serotonergic transmission appear to have only a moderate and, in some cases, transient effects on the body weight.
The 5-HT2c receptor subtype has also been suggested to be involved in CNS disorders such as depression and anxiety (Exp. Opin. Invest. Drugs 1998, 7, 1587-1599; IDrugs 1999, 2, 109-120).
The 5-HT2c receptor subtype has further been suggested to be involved in urinary disorders such as urinary incontinence (IDrugs 1999, 2, 109-120).
Compounds which have a selective effect on the 5-HT2c receptor may therefore have a therapeutic potential in the treatment of disorders like those mentioned above. Of course, selectivity also reduces the potential for adverse effects mediated by other serotonin receptors.
U.S. Pat. No. 3,253,989 discloses the use of mCPP as an anorectic agent.
EP-A1-863 136 discloses azetidine and pyrrolidine derivatives which are selective 5-HT2c receptor agonists having antidepressant activity and which can be used for treating or preventing serotonin-related diseases, including eating disorders and anxiety.
EP-A-657 426 discloses tricyclic pyrrole derivatives having activity on the 5-HT2c receptor and which inter alia may be used for treating eating disorders.
EP-A-655 440 discloses l-aminoethylindoles having activity on the 5-HT2c receptor and which may be used for treating eating disorders.
EP-A-572 863 discloses pyrazinoindoles having activity on the 5-HT2c receptor and which may be used for treating eating disorders.
J. Med. Chem. 1978, 21, 536-542 and U.S. Pat. No. 4,081,542 disclose a series of piperazinylpyrazines having central serotonin-mimetic activity.
J. Med. Chem. 1981. 24, 93-101 discloses a series of piperazinylquinoxalines with central serotoninmimetic activity.
WO 00/12475 discloses indoline derivatives as 5-HT2b and/or 5-HT2C receptor ligands, especially for the treatment of obesity.
WO 00/12510 discloses pyrroloindoles, pyridoindoles and azepinoindoles as 5-HT2c receptor agonists, particluarly for the treatment of obesity.
WO 00/12482 discloses indazole derivatives as selective, directly active 5-HT2c receptor ligands, preferably 5-HT2c receptor agonists, particularly for use as anti-obesity agents.
WO 00/12502 discloses pyrroloquinolines as 5-HT2c receptor agonists, particularly for use as anti-obesity agents.
WO 00/35922 discloses 2,3,4,4a-tetrahydro-1H-pyrazino[1,2-a]quinoxalin-5(6H)ones as 5HT2c agonists, which may be used for the treatment of obesity.
WO 00/44737 discloses aminoalkylbenzofurans as 5-HT2c agonists, which may be used for the treatment of obesity.
Further compounds reported to be 5HT2c receptor agonists are, for example, indazolylpropylamines of the type described in WO 00/12481; indazoles of the type described in WO 00/17170; piperazinylpyrazines of the type described in WO 00/76984; heterocycle fused xcex3-carbolines of the type described in WO 00/77001, WO 00/77002 and WO 00/77010; benzofurylpiperazines of the type described in WO 01/09111 and WO 01/09123; benzofurans of the type described in WO 01/09122; benzothiophenes of the type described in 01/09126; aminoalkylindazoles of the type described in WO 98/30548; indoles of the type described in WO 01/12603; indolines of the type described in WO 01/12602; pyrazino(aza)indoles of the type described in WO 00/44753 and tricyclic pyrroles or pyrazoles of the type described in WO 98/56768.
GB-B-1,457,005 discloses 1-piperazinyl-2-[2-(phenyl)ethenyl]-quinoxaline derivatives which exhibit anti-inflammatory activity.
Chem. Pharm. Bull. 1993, 41(10) 1832-1841 discloses 5-HT3 antagonists including 2-(4-methyl-1 -piperazinyl)-4-phenoxyquinoxaline.
GB-B-1,440,722 discloses 2-(1xe2x80x2-piperazinyl)-quinoxaline compounds having pharmaceutical activity against depression.
WO 96/11920 discloses CNS-active pyridinylurea derivatives.
WO 95/01976 discloses indoline derivatives active as 5-HT2c antagonists and of potential use in the treatment of CNS disorders.
WO 97/14689 discloses arylpiperazine cyclic amine derivatives, which are selective 5-HT1d receptor antagonists.
WO 98/42692 discloses piperazines derived from cyclic amines, which are selective antagonists of human 5-HT1a, 5-HT1d and 5-HT1b receptors.
GB-B-1,465,946 discloses substituted pyridazinyl, pyrimidinyl and pyridyl compounds which are active as xcex2-receptor blocking agents.
EP-A-711757 discloses [3-(4-phenyl-piperazin-1-yl)propylamino]-pyridine, pyrimidine and benzene derivatives as xcex1-adrenoceptor antagonists.
WO 99/03833 discloses arylpiperazine derivatives, which are 5-HT2 antagonists and 5-HT1a receptor agonists and therefore are useful as remedies or preventives for psychoneurosis.
WO 96/02525 discloses arylpiperazine-derived piperazide derivatives having 5-HT receptor antagonistic activity.
WO 99/58490 disloses aryl-hydronaphthalen-alkane amines which may effectuate partial or complete blockage of serotonergic 5-HT2c receptors in an organism.
It is an object of the present invention to provide new compounds.
Another object of the invention is a pharmaceutical composition comprising compounds for use in therapy as an active ingredient.
Finally, an object of the invention is a method of treatment or prophylaxis of a serotonin related disease, especially a disease related to the 5-HT2c receptor.
According to the invention novel compounds of the general formula (I) are provided:
wherein
R1 is hydrogen, C1-C4-alkyl, C3-4-alkenyl, C1-4-acyl, C1-4-alkoxycarbonyl, 2-hydroxyethyl, 2-cyanoethyl, tetrahydropyran-2-yl, or a nitrogen protecting group;
R2 is hydrogen, C1-4-alkyl, hydoxymethyl, C1-4-alkoxymethyl, or fluoromethyl;
R3 and R4 independently of each other are hydrogen, halogen, methyl, C1-4-alkyl, aryl, heteroaryl wherein aryl and heteroaryl residues in turn may be substituted in one or more positions independently of each other by halogen, C1-4-alkyl, C1-4-alkoxy, C1-4-alkylthio, C1-4-alkylsulphonyl, methanesulphonamido, acetyl, nitro, cyano, hydroxy, trifluoromethyl, trifluoromethoxy, trifluoromethylthio, amino, methylamino, dimethylamino, or acetamido; or
R3 and R4 together with the carbon atoms to which they are bound form a 5- or 6-membered aromatic or heteroaromatic ring, which optionally is independently substituted in one or more positions by halogen, methyl, methoxy, methylthio, methylsulphonyl, nitro, cyano, hydroxy, trifluoromethyl, trifluoromethylthio, amino, methylamino, dimethylamino or acetamido;
R5 and R6 independently of each other are hydrogen, C1-C4-alkoxy-C2-C4-alkyl, hydroxy-C2-C4-alkyl, C1-C6-alkyl, C2-C6-acyl, aryl, heteroaryl, aryl-C1-C2-alkyl, heteroaryl-C1-C2-alkyl, aryl-C1-C2-acyl, heteroaryl-C1-C2-acyl, and wherein any aryl or heteroaryl, alone or as part of another group, may be independently substituted in one or more positions by C1-4-alkyl, C1-4-alkoxy, C1-4-alkylthio, C2-4-acyl, C1-4-alkylsulphonyl, cyano, nitro, hydroxy, C2-3-alkenyl, C2-3-alkynyl, fluoromethyl, trifluoromethyl, trifluoromethoxy, halogen, dimethylamino, or methylamino; or
R5 and R6 together with the nitrogen atom to which they are bound form a saturated heterocyclic ring having 4-7 ring members which ring may contain an additional heteroatom and which may be substituted by methyl, oxo or hydroxy;
R7 is hydrogen or a substituent selected from halogen, methyl, methoxy, and ethoxy; and
n=1xe2x88x923;
and pharmaceutically acceptable salts, hydrates, geometrical isomers, tautomers, optical isomers, N-oxides and prodrug forms thereof.
In case the compounds of formula (I) can be in the form of optical isomers, the invention comprises the racemic mixture as well as the individual enantiomers as such.
In case the compounds of formula (I) contain groups which may exist in tautomeric forms, the invention comprises the tautomeric forms of the compounds as well as mixtures thereof.
In case the compounds of formula (I) can be in the form of geometrical isomers, the invention comprises the geometrical isomers as well as mixtures thereof.
In another aspect, this invention provides a method for preparing a compound of this invention. The method includes converting a compound of formula (II):
to the just-mentioned compound.
In formula (II), R3 and R4 independently of each other are hydrogen, halogen, methyl, C1-4-alkyl, aryl, heteroaryl wherein aryl and heteroaryl residues in turn may be substituted in one or more positions independently of each other by halogen, C1-4-alkyl, C1-4-alkoxy, C1-4-alkylthio, C1-4-alkylsulphonyl, methanesulphonamido, acetyl, nitro, cyano, hydroxy, trifluoromethyl, trifluoromethoxy, trifluoromethylthio, amino, methylamino, dimethylamino or acetamido; or
R3 and R4 together with the carbon atoms to which they are bound form a 5- or 6-membered aromatic or heteroaromatic ring, which may be substituted in one or more positions by halogen, methyl, methoxy, methylthio, methylsulphonyl, nitro, cyano, hydroxy, trifluoromethyl, trifluoromethylthio, amino, methylamino, dimethylamino or acetamido; and
each of Hal1 and Hal2, independently, is halogen.
In further another aspect, the invention provides the compounds according to formula (I) above for use in therapy.
Still another aspect of the invention provides a pharmaceutical composition comprising a compound according to formula (I) above as the active ingredient, preferably together with a pharmaceutically acceptable carrier and, if desired, other pharmacologically active agents.
In yet another aspect, the invention provides a method for the treatment of a human or animal subject suffering from a serotonin-related disease, particularly 5-HT2c receptor-related, especially eating disorders, particularly obesity; memory disorders, schizophrenia, mood disorders, anxiety disorders, pain, substance abuse, sexual dysfunctions, epilepsy and urinary disorders.
Another aspect of the invention provides the use of the compounds according to formula (I) above for the manufacture of a medicament for the treatment of a serotonin-related disease, particularly 5-HT2c receptor-related, especially eating disorders, particularly obesity; memory disorders; schizophrenia, mood disorders, anxiety disorders, pain, substance abuse, sexual dysfunctions, epilepsy and urinary disorders.
Finally a method for modulating 5HT2c receptor function is an aspect of the invention.
According to the present invention, a class of novel compounds has been developed which bind to the 5-HT2c receptor (agonists or antagonists) and which therefore may be used for the treatment of serotonin-related disorders.
First, the various terms used, separately and in combinations, in the above definition of the compounds having the general formula (I) will be explained.
By xe2x80x9cheteroatomxe2x80x9d is meant nitrogen, oxygen, sulphur, and in heteroaromatic rings, also selenium.
The term xe2x80x9carylxe2x80x9d includes phenyl, 1-naphthyl and 2-naphthyl.
The term xe2x80x9cheteroarylxe2x80x9d includes five- and six-membered heteroaromatic rings such as pyrrole, imidazole, thiophene, furan, selenophene, thiazole, isothiazole, thiadiazole, oxazole, isoxazole, oxadiazole, pyridine, pyrazine, pyrimidine, pyridazine, pyrazole, triazole and tetrazole.
C1-6-alkyl, which may be straight or branched, is preferably C1-4-alkyl. Exemplary alkyl groups include methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, isopentyl, hexyl, and isohexyl.
C1-4-alkoxy may be straight or branched. Exemplary alkoxy groups include methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy and tert-butoxy.
C2-4-alkenyl may be straight or branched. Exemplary alkenyl groups include vinyl, 2-propenyl and 1-methyl-2-propenyl.
C1-C4-alkoxy-C2-C4-alkyl may be straight or branched. Exemplary groups include 2-(methoxy)ethyl, 3-methoxy-1-propyl, 4-ethoxy-1-butyl and the like.
Exemplary aryl-C1-C2-acyl include benzoyl and phenylacetyl. Exemplary heteroaryl-C1-C2-acyl include nicotinoyl and 3-pyridinylacetyl and the like.
C2-4-acyl may be saturated or unsaturated. Exemplary acyl groups include acetyl, propionyl, butyryl, isobutyryl, and butenoyl (e.g. 3-butenoyl).
Halogen includes fluorine, chlorine and bromine.
Where it is stated above that aryl and heteroaryl residues may be substituted, this applies to aryl and heteroaryl per se as well as to any combined groups containing aryl or heteroaryl residues, such as heteroaryl-C1-C2-alkyl and aryl-C1-C2-acyl.
The term xe2x80x9cN-oxidesxe2x80x9d means that one or more nitrogen atoms, when present in a compound, are in N-oxide form (Nxe2x86x92O).
The term xe2x80x9cprodrug formsxe2x80x9d means a pharmacologically acceptable derivative, such as an ester or an amide, which derivative is biotransformed in the body to form the active drug. Reference is made to Goodman and Gilman""s, The Pharmacological basis of Therapeutics, 8th ed., McGraw-Hill, Int. Ed. 1992, xe2x80x9cBiotransformation of Drugs, p. 13-15.
xe2x80x9cPharmaceutically acceptablexe2x80x9d means being useful in preparing a pharmaceutical composition that is generally safe, non-toxic and neither biologically nor otherwise undesirable and includes being useful for veterinary use as well as human pharmaceutical use.
xe2x80x9cPharmaceutically acceptable saltsxe2x80x9d mean salts which are pharmaceutically acceptable, as defined above, and which possess the desired pharmacological activity. Such salts include acid addition salts formed with organic and inorganic acids, such as hydrogen chloride, hydrogen bromide, hydrogen iodide, sulfuric acid, phosphoric acid, acetic acid, glycolic acid, maleic acid, malonic acid, oxalic acid, toluenesulphonic acid, methanesulphonic acid, fumaric acid, succinic acid, tartaric acid, citric acid, benzoic acid, ascorbic acid, and the like.
R1 is preferably hydrogen or methyl. Most preferably R1 is hydrogen.
R1 may also serve as a nitrogen protecting group, and then R1 is t-butoxycarbonyl (t-BOC), benzyl, or trityl.
R2 is preferably hydrogen or methyl (especially in the 2-position of the piperazine ring).
R3 and R4 are preferably (independently) hydrogen, halogen or methyl. When R3 and R4 form a ring together with the ring carbons to which they are bound, such a ring is preferably benzene (to give quinoxaline) or thiophene (to give thieno[3,4-b]pyrazine). When substituted, the rings are preferably mono- or disubstituted, preferably by halogen or methyl.
When R7 is other than hydrogen it may occupy any available position of the phenyl ring.
The group xe2x80x94CH2N(R5)(R6) may be attached to the orto-, meta-, or the para position, relative to the alkylenedioxy side-chain, of the phenyl ring, preferably the meta position.
n in formula (I) is 1xe2x88x923 where n is the number of methylene groups n is preferably 1, having the meaning that the two oxygen atoms in formula (I) are spaced between a xe2x80x94CH2CH2xe2x80x94 group;
Preferred compounds of the general formula (I) above are:
2-(1-Piperazinyl)-3-{2-[3-(4-morpholinylmethyl)phenoxy]ethoxy}pyrazine;
2-(1-Piperazinyl)-3-{2-[3-(1-pyrrolidinylmethyl)phenoxy]ethoxy}pyrazine;
2-(1-Piperazinyl)-3-{2-[3-(4-methyl-1-piperazinylmethyl)phenoxy]ethoxy}pyrazine;
2-(1-Piperazinyl)-3-{2-[3-{(2-methoxyethyl)amino}methyl)phenoxy]ethoxy}pyrazine;
2-(1-Piperazinyl)-3-{2-[3-{(isopropylamino)methyl}phenoxy]ethoxy}pyrazine,
and their pharmacologically acceptable salts and solvates.
In another aspect, this invention relates to compounds of any of the formulae herein and their use as delineated herein, wherein R5 and R6 together with the nitrogen atom to which they are bound form a saturated heterocylic ring having 4-7 ring members, and which may contain an additional heteratom. Exemplary rings are azetidine, pyrrolidine, piperazine, homopiperazine, morpholine, thiomorpholine, or piperidine. The saturated heterocyclic ring may be substituted by methyl, oxo, or hydroxy.
As mentioned above, the compounds of the present invention are useful for the treatment (including prophylactic treatment) of serotonin-related disorders, especially 5-HT2c receptor-related, in a human being or in an animal (including e.g. pets), such as eating disorders, especially obesity; memory disorders, such as Alzheimer""s disease; schizophrenia; mood disorders, including, but not restricted to, major depression and bipolar depression, including both mild and manic bipolar disorder, seasonal affective disorder (SAD); anxiety disorders, including situational anxiety, generalised anxiety disorder, primary anxiety disorders (panic disorders, phobias, obsessive-compulsive disorders, and post-traumatic stress disorders), and secondary anxiety disorders (for example anxiety associated with substance abuse); pain; substance abuse; sexual dysfunctions; epilepsy and urinary disorders, such as urinary incontinence.
The compounds of the present invention in radiolabeled form, may be used as a diagnostic agent.
The compounds of the general formula (I) above may be prepared by a method of this invention, or by, in analogy with, a conventional method. This invention relates to methods of making compounds of any formulae herein comprising reacting any one or more of the compounds or formulae delineated herein including any processes delineated herein.
For example, as shown in Scheme 1, a compound of formula (I) may be prepared by first treating a compound of formula (II), wherein Hal is halogen and R3 and R4 are as defined above, with an appropriate piperazine of formula (III), wherein R1 and R2 have the same meaning as in formula (I) and where R1 may be a suitable nitrogen protecting group, such as trityl, benzyl or tert-butoxycarbonyl, to provide a compound of formula (IV). The reaction is carried out in a solvent, such as, acetonitrile, dioxane, tetrahydrofuran (THF), n-butanol, N,N-dimethylformamide (DMF), or in a mixture of solvents such as DMF/dioxane, optionally in the presence of a base, such as K2CO3, Na2CO3, Cs2CO3, NaOH, triethylamine, pyridine, or the like, at 0-200xc2x0 C. for 1-24 hours.
The compound of formula (IV) is reacted with a diol of formula (V), wherein n has the same meaning as in formula (I), to provide intermediate (VI). The reaction is carried out in a solvent, such as, dioxane, THF, DMF or pyridine, and the like, in the presence of a base such as K-t-BuO, Na-t-BuO, NaH, or the like, at 0-150xc2x0 C. for 1-24 hours.
Intermediate (VI) is reacted with a hydroxybenzaldehyde compound of formula (VII), wherein R7 has the same meaning as in formula (I), to provide the aldehyde intermediate (VIII). The reaction may be carried out in the presence of diethyl azodicarboxylate (DEAD) or 1,1xe2x80x2-azobis(N,N-dimethylfornamide) (cf. Tetrahedron Lett. 1995, 36, 3789-3792), preferably DEAD, and triphenylphosphine (PPh3) in a solvent such as THF or dichloromethane (Mitsunobu reaction; see: Org. React. 1992, 42, 335-656.).
Subjecting intermediate (VIII) to a standard reductive alkylation procedure (such as described in J. Org. Chem. 1996, 61, 3849-3862), with an appropriate amine of formula (IX), wherein R5 and R6 have the same meaning as in formula (I), results in a compound of this invention (I).
When R1 in formula (I) is a nitrogen protecting group as defined below, the subsequent N-deprotection may be performed under standard conditions, such as those described in Protective Groups in Organic Synthesis, John Wiley and Sons, 1991, to provide compounds of formula (I) wherein R1 is hydrogen. Nitrogen protecting groups are known in the art and include those described in T. W. Greene and P. G. M. Wuts, Protective Groups in Organic Synthesis, 2d. Ed., John Wiley and Sons (1991) and subsequent editions thereof.
An obtained compound of formula (I) may be converted to another compound of formula (I) by methods well known in the art.
The processes described above may be carried out to give a compound of the invention in the form of a free base or as an acid addition salt. A pharmaceutically acceptable acid addition salt may be obtained by dissolving the free base in a suitable organic solvent, such as ether or in a mixture of ether and methanol, and treating the solution with an acid, in accordance with conventional procedures for preparing acid addition salts from base compounds. Examples of addition salt forming acids are maleic acid, fumaric acid, succinic acid, methanesulfonic acid, acetic acid, oxalic acid, benzoic acid, hydrochloric acid, sulphuric acid, phosphoric acid, and the like.
The compounds of formula (I) may possess one or more chiral carbon atoms, and they may therefore be obtained in the form of optical isomers, e.g., as a pure enantiomer, or as a mixture of enantiomers (racemate) or as a mixture containing diastereomers. The separation of mixtures of optical isomers to obtain pure enantiomers is well known in the art and may, for example, be achieved by fractional crystallization of salts with optically active (chiral) acids or by chromatographic separation on chiral columns.
In accordance with the present invention, the compounds of formula (I), in the form of free bases or salts with physiologically acceptable acids, can be brought into suitable galenic forms, such as compositions for oral use, for injection, for nasal spray administration or the like, in accordance with accepted pharmaceutical procedures. Such pharmaceutical compositions according to the invention comprise an effective amount of the compounds of formula (I) in association with compatible pharmaceutically acceptable carrier materials, or diluents, as are well known in the art. The carriers may be any inert material, organic or inorganic, suitable for enteral, percutaneous, subcutaneous or parenteral administration, such as: water, gelatin, gum arabicum, lactose, microcrystalline cellulose, starch, sodium starch glycolate, calcium hydrogen phosphate, magnesium stearate, talcum, colloidal silicon dioxide, and the like. Such compositions may also contain other pharmacologically active agents, and conventional additives, such as stabilizers, wetting agents, emulsifiers, flavouring agents, buffers, and the like.
The compositions according to the invention can e.g. be made up in solid or liquid form for oral administration, such as tablets, pills, capsules, powders, syrups, elixirs, dispersable granules, cachets, suppositories and the like, in the form of sterile solutions, suspensions or emulsions for parenteral administration, sprays, e.g. a nasal spray, transdermal preparations, e.g. patches, and the like.
As mentioned above, the compounds of the invention may be used for the treatment of serotonin-related disorders in a human being or an animal, such as eating disorders, particularly obesity, memory disorders, schizophrenia, mood disorders, anxiety disorders, pain, substance abuse, sexual dysfunctions, epilepsy and urinary disorders. The dose level and frequency of dosage of the specific compound will vary depending on a variety of factors including the potency of the specific compound employed, the metabolic stability and length of action of that compound, the patient""s age, body weight, general health, sex, diet, mode and time of administration, rate of excretion, drug combination, the severity of the condition to be treated, and the patient undergoing therapy. The daily dosage may, for example, range from about 0.001 mg to about 100 mg per kilo of body weight, administered singly or multiply in doses, e.g. from about 0.01 mg to about 25 mg each. Normally, such a dosage is given orally but parenteral administration may also be chosen.
The specific examples below are to be construed as merely illustrative, and not limitative of the remainder of the disclosure in any way whatsoever. Without further elaboration, it is believed that one skilled in the art can, based on the description herein, utilize the present invention to its fullest extent. All publications cited herein are hereby incorporated by reference in their entirety.

Abstract: wherein R1, R2 and R3 are as described in the specification, which compounds are ligands to the serotonin 5-HT2c receptor.


The disclosure provides methods to mitigate and/or eliminate problems associated with removal of carbon-based resists from organic low k dielectrics. The methods include forming an organic low k dielectric layer over a semiconductor substrate, forming a capping layer over the organic low k dielectric layer, forming a silicon-containing resist over the capping layer, patterning the silicon-containing resist layer to expose portions of the capping layer and to form a patterned silicon oxide layer, removing the organic low k dielectric layer to form one or more openings, and removing the patterned silicon oxide layer. The silicon-containing resist facilitates efficient patterning of the organic low k-dielectric layers, and thereby increases the performance and cost-effectiveness of semiconductor devices fabricated using organic low k dielectrics.

Continuing demand for smaller and lighter electronics has created a need for advanced materials and designs. This is because current trends in electronic markets, such as the growing demand for wireless communications and portable computing, are placing an increasing emphasis on smaller/lighter device features and faster operating speeds. To ensure reliable operation of an electronic circuit, proper electrical isolation between adjacent conductors must be achieved. Proper electrical isolation mitigates high voltage arcing and leakage currents, which can be exacerbated at high frequencies. As device density on chips increases, the difficulty in achieving proper electrical isolation also increases.
As the wafer size increases and/or as transistor device size decreases, concerns over the interlayer dielectric material become more important. Current interlayer dielectric materials, such as inorganic oxides and nitrides, have beneficial aspects as well as deficiencies. It is more important to account for certain physical properties, such as unwanted diffusion, crosstalk, adequate insulation (both electrical and temperature), coefficients of thermal expansion, short channel effects, leakage, critical dimension control, drain induced barrier lowering, and the like, when making circuit designs.
Thus, there is a need in the art for materials that provide better insulation, and methods and systems for integrating those materials into the fabrication processes of semiconducting devices.

Silicon-containing resist to pattern organic low k-dielectrics


In a printer-processor, if an error occurs during execution of a print process, a corresponding error message is displayed in a display unit, and the error message and the time at which the error occurs are stored sequentially in a memory. In response to an instruction, the errors that have occurred are displayed one after another in the order stored, or in the reverse order to review the record of past errors.

The present invention relates to a method of storing and displaying error information so as to utilize the information for maintaining a photographic printer.
In current photographic printers an error message is indicated in a display attached to the photographic printer each time a fault or trouble occurs in the printer. Some kinds of errors, caused by faults such as burn-out of a printing lamp, need preparation or adjustment which can be carried out only by a maintenance service staff of the manufacturer. With such errors, the service staff asks the operator what kind of error has occurred. The staff then tries to fix the printer based on the operator s explanation. Also, in routine maintenance, the service staff usually requires the operator to explain the operational condition of the printer before checking or adjusting each section of the printer.
In order to fix the printer completely, it is important to know the record of past errors, namely the history of errors besides the present error. However, most operators cannot remember all the past error messages, or cannot explain past errors accurately.

Method of storing and displaying error information in photographic printer


The present invention provides a controller positioning structure for a vehicle in which the controller such as a shift lever can be positioned at a front to rear position that is optimum for the driver. Since the shift lever or controller is movable in the front to rear direction and stoppable at any desired position, the driver can adjust the front to rear position of the shift lever at the optimum position. Therefore, operation of the shift lever is made easy.

1. Field of the Invention
The present invention relates to an arrangement of a controller such as a shifting controller that is operated from a driver""s seat of a vehicle. More specifically, the present invention relates to a controller that can be selectively positioned within a predetermined range in a front to rear direction of the vehicle that is optimum for the driver.
2. Background Information
Typically, a shift lever that outputs a transmission signal to the transmission is located on one side of the driver""s seat in an automobile. Thus, the shift lever is provided as a xe2x80x9ccontrollerxe2x80x9d for the transmission. The shift lever often electronically operates the transmission. Specifically, by tilting the shift lever in a forward direction or in a rearward direction, an electromechanical signal is sent to the transmission, such that the driver can select a desired transmission gear. This type of arrangement is disclosed in Japanese Laid-Open Patent Application No. 6-70405. A shift lever of this type is typically located in a center console or an armrest, which is provided on one side of the driver""s seat. The front to rear position of the shift lever is fixed to the vehicle.
In view of the above, there exists a need for an improved controller structure. This invention addresses this need in the art as well as other needs, which will become apparent to those skilled in the art from this disclosure.
It has been discovered that in a conventional shift lever arrangement, the driver""s seat moves in a front to rear direction to conform to the driver""s size and driving posture. However, the front to rear position of the shift lever is fixed. As a result, when a small driver moves the driver""s seat to the most forward position, the shift lever may be positioned too far to the rear of the driver""s seat for the small driver to use comfortably. Similarly, when a large driver moves the driver""s seat to the most rearward position, the shift lever may be positioned too forward of the driver""s seat for the large driver to use comfortably. Accordingly, the front to rear position of the shift lever may not be the optimum one for the driver.
This invention has been conceived in view of the shortcomings of the conventional technology described above. Thus, one object of the present invention is to provide a controller positioning structure for a vehicle in which the controller, such as a shift lever, can be moved to an optimum front to rear position for a particular driver.
The foregoing object can be attained by providing a controller positioning structure for a vehicle, comprising a controller and a controller moving mechanism. The controller is configured to output a vehicle control signal. The controller moving mechanism is configured to be mounted adjacent a lateral side of a driver""s seat of the vehicle. The controller moving is configured to selectively move in a front to rear direction of the vehicle and to selectively stop at any desired position within a front to rear movable range. The controller moving mechanism is operatively coupled to the controller such that the controller moves in the front to rear direction of the vehicle.
These and other objects, features, aspects and advantages of the present invention will become apparent to those skilled in the art from the following detailed description, which, taken in conjunction with the annexed drawings, disclose a preferred embodiments of the present invention.

Controller positioning structure for vehicle


Methods and systems to perform a computer task in a reduced power consumption state, including to virtualize physical resources with respect to an operating environment and service environment, to exit the operating environment and enter the service environment, to place a first set of one or more of the physical resources in a reduced power consumption state, and to perform a task in the service environment utilizing a processor and a second set of one or more of the physical resources. A physical resource may be assigned to an operating environment upon an initialization of the operating environment, and re-assigned to the service environment to be utilized by the service environment while other physical resources are placed in a reduced power consumption state.

Computer systems include a plurality of physical resources that consume electrical power.
A computer system may include a system-wide power-save feature to place all or substantially all physical resources, including an instruction processor, in a reduced-power or sleep state.
During normal operation, a computer system may utilize one or more physical resources when performing a task, during which one or more other physical resources may not be utilized. For example, a data transfer between a storage device and a network may utilize the storage device and a network interface card, but may not utilize other physical resources, such as a display, a printer, a keyboard, and other physical resources.
Where a computer task may take a relatively long period of time to complete, such a as a relatively large data transfer, or where the task may be performed when the computer is not needed for other purposes, maintaining non-utilized physical resources in active states unnecessarily consumes power.
In the drawings, the leftmost digit(s) of a reference number identifies the drawing in which the reference number first appears.


The present invention relates, in general, to the treatment of estrogen-dependent diseases and disorders and, in particular, to a method of treating estrogen-dependent cancers, particularly breast cancer, with antiestrogens.

The human estrogen receptor (ER) is a member of the nuclear receptor superfamily of transcription factors (Evans, Science 240:889-895 (1988)). In the absence of hormone, it resides in the nucleus of target cells in a transcriptionally inactive state. Upon binding ligand, ER undergoes a conformational change initiating a cascade of events leading ultimately to its association with specific regulatory regions within target genes (O'Malley et al, Hormone Research 47:1-26 (1991)). The ensuing effect on transcription is influenced by the cell and promoter context of the DNA-bound receptor (Tora et al, Cell 59:477-487 (1989) (Tasset et al, Cell 62:1177-1187 (1990); McDonnell et al, Mol. Endocrinol. 9:659-669 (1995); Tzukerman et al, Mol. Endocrinol. 8:21-30 (1994)). It is in this manner that the physiological ER-agonist, estradiol, exerts its biological activity in the reproductive, skeletal and cardiovascular systems (Clark and Peck, Female Sex Steroids:Receptors and Functions (eds) Monographs on Endocrinology, Springer-Verlag, New York (1979); Chow et al, J. Clin. Invest. 89:74-78 (1992); Eaker et al, Circulation 88:1999-2009 (1993)).
In addition to these activities, estrogen has been shown to function as a mitogen in most ER-positive breast cancer cells. Thus, treatment regimens which include antiestrogens, synthetic compounds which oppose the actions of estrogen, have been effective clinically in halting or delaying the progression of the disease (Jordan and Murphy, Endocrine Reviews 11:578-610 (1990); Parker, Breast Cancer Res. Treat. 26:131-137 (1993)). The availability of these synthetic ER-modulators and subsequent dissection of their mechanism(s) of action have provided useful insights into ER action.
One of the most studied compounds in this regard is tamoxifen (Jordan and Murphy, Endocrine Reviews 11:578-610 (1990)). This compound functions as an antagonist in most ER-positive breast tumors, but displays a paradoxical agonist activity in bone and the cardiovascular system and partial agonist activity in the uterus (Kedar et al, Lancet 343:1318-1321 (1994); Love et al, New Engl. J. Med. 326:852-856 (1992); Love et al, Ann. Intern. Med. 115:860-864 (1991)). Thus, the agonist/antagonist activity of the ER-tamoxifen complex is influenced by cell context. This important observation is in apparent contradiction to long-standing models that hold that ER only exists in the cell in an active or an inactive state (Clark and Peck, Female Sex Steroids:Receptors and Functions (eds) Monographs on Endocrinology, Springer-Verlag, New York (1979)). It indicates instead that different ligands acting through the same receptor can manifest different biologies in different cells. Definition of the mechanism of this selectivity is likely to advance the understanding of processes such as tamoxifen resistance, observed in most ER-containing breast cancers, where abnormalities in ER-signaling are implicated (Tonetti and Jordan, Anti-Cancer Drugs 6:498-507 (1995)).
Using an in vitro approach, the likely mechanism for the cell selective agonist/antagonist activity of tamoxifen has been determined (Tora et al, Cell 59:477-487 (1989); Tasset et al, Cell 62:1177-1187 (1990); McDonnell et al, Mol. Endocrinol. 9:659-669 (1995); Tzukerman et al, Mol. Endocrinol. 8:21-30 (1994)). Importantly, it has been shown that tamoxifen induces a conformational change within ER which is distinct from that induced by estradiol (McDonnell et al, Mol. Endocrinol. 9:659-669 (1995); (Beekman et al, Molecular Endocrinology 7:1266-1274 (1993)). Furthermore, determination of the sequences within ER required for transcriptional activity indicate how these specific ligand-receptor complexes are differentially recognized by the cellular transcriptional machinery. Specifically, it has been shown that ER contains two activation domains, AF-1 (Activation Function-1) and AF-2, which permit its interaction with the transcription apparatus. The relative contribution of these AFs to overall ER efficacy differs from cell to cell (Tora et al, Cell 59:477-487 (1989); McDonnell et al, Mol. Endocrinol. 9:659-669 (1995); Tzukerman et al, Mol. Endocrinol. 8:21-30 (1994)). Estradiol was determined to function as both an AF-1 and an AF-2 agonist, in that it exhibited maximal activity regardless of which AF was dominant in a given cellular environment. Tamoxifen, on the other hand, functions as an AF-2 antagonist, inhibiting ER activity in cells where AF-2 is required or is the dominant activator (Tora et al, Cell 59:477-487 (1989); McDonnell et al, Mol. Endocrinol. 9:659-669 (1995); Tzukerman et al, Mol. Endocrinol. 8:21-30 (1994)). Conversely, tamoxifen functions as an agonist when AF-1 alone is required (McDonnell et al, Mol. Endocrinol. 9:659-669 (1995); Tzukerman et al, Mol. Endocrinol. 8:21-30 (1994)). Subsequently, based on their relative AF-1/AF-2 activity, four mechanistically distinct groups of ER-modulators were defined; full agonists (i.e. estradiol), two distinct classes of partial agonists, represented by tamoxifen and raloxifene, and the pure antagonists, of which ICI182,780 is a representative member (McDonnell et al, Mol. Endocrinol. 9:659-669 (1995); Tzukerman et al, Mol. Endocrinol. 8:21-30 (1994)). These results provide a mechanistic explanation for the observed differences in the biological activities of some ER-modulators and indicate that the mechanism by which ER operates in different tissues is not identical. Interestingly, the agonist activity exhibited by ER-modulators, such as estrogen and tamoxifen, in these in vitro systems reflects their activity in the reproductive tracts of whole animals. This correlation does not extend to bone, however, where estradiol, tamoxifen and raloxifene, which display different degrees of AF-1/AF-2 agonist activity, all effectively protect against bone loss in the ovariectomized rat model. Thus, with the exception of the steroidal pure antiestrogens (ie, ICI182,780), all known classes of ER modulators appear to protect against bone loss in humans and relevant animal models, while they display different degrees of estrogenic activity in other tissues (Chow et al, J. Clin. Invest. 89:74-78 (1992); Love et al, New Engl. J. Med. 326:852-856 (1992); Draper et al, Biochemical Markers of Bone and Lipid Metabolism in Healthy Postmenopausal Women. In:C. Christiansen and B. Biis (eds) Proceedings 1993. Fourth International Symposium on Osteoporosis and Consensus Development Conference, Handelstrykkeriet, Aalborg; Wagner et al, Proc. Natl. Acad. Sci. USA 93:8739-8744 (1996); Black et al, J. Clin. Invest 93:63-69 (1994)).

Method of preventing or treating estrogen-dependent diseases and disorders


A baler with a rectangular baling chamber and in which a baling piston is accommodated. A supply channel with a supply arrangement for the conveying and compressing of crop in the supply channel and for bringing the compressed harvested crop into the baling chamber and with a sensor arrangement for the determination of the loading on at least one component of the baler. The crop to be baled is pre-compressed in the supply channel by a compression fork before it is pushed into the baling chamber by a loading fork. The sensor arrangement is configured in such a way that it detects or can detect one or more values that represent the distribution of the harvested crop with respect to the width of the supply channel.

1. Field of Invention
This invention generally relates to a baler and, more particularly, to a baler having a sensor arrangement for determination of at least one value representing the throughput or distribution of harvested crop with regard to the width of the supply channel.
2. Related Technology
German Patent Reference No. DE A1 195 43 343 shows an agricultural baler for the production of large rectangular bales. This baler is provided with a weighing arrangement that weighs the finished bound bale of harvested crop. The baler is equipped with sensor technology for the determination of the relative loading value of the operating devices of the baler using strain gages, rotational speed sensors, pressure sensors or temperature sensors.
The general purpose of the present invention overcomes problems in the prior art by providing a baler delivering regularly formed bales. In the prior art, the supply of harvested crop to balers is frequently not optimal, therefore the balers routinely deliver irregularly formed bales.


To print a certified document, a user may select or a system may receive a selection of a document to be certified. The system identifies a security template to be used based on the document and/or capabilities of the print device on which the document will be printed. The system may display the document with a non-secure overlay of the selected security template, add a unique security element to the document according to the template, and cause the document to be printed at the selected print device with the added security element without permitting the added security element to be fully displayed or printed on any other device.

The process of creating a certified copy of a document requires several time- and resource-consuming steps, such as manually affixing a seal to the document. In many cases, these steps may certify the physical document—i.e., the substrate on which the information is printed—but not necessarily the information itself. For example, a seal affixed to a document may authenticate the physical paper, but it does not protect someone from altering the information printed on the paper. For documents such as birth certificates, regulatory permits, and other legal document, protecting the information is often more important than protecting the physical document itself.
This document describes improved methods and systems for generating certified copies of documents.

System for creating certified document copies


The present invention relates to a method for the polymerization of cycloolefins by ring-opening metathesis. The reaction is carried out in the presence of at least one particular catalyst, selected from the ruthenium alkylidene complexes comprising at least one 1-aryl-3-cycloalkyl-imidazolin-2-ylidene ligand and mixtures thereof. The invention also relates to a kit for implementing this method.

Polydicyclopentadiene or p-DCPD is a polyolefin that is valued for its light weight, rigidity and properties of impact strength, corrosion resistance and resistance to deformation at high temperature. It is mainly used in the manufacture of parts with large dimensions such as body elements for tractors, buses or trucks.
p-DCPD is generally obtained by ring-opening metathesis of DCPD (or ROMP for "Ring-Opening Metathesis Polymerization"), followed by crosslinking, leading to the following product:

This transformation is generally carried out in a mold by the so-called reaction injection molding (RIM) technique.
The metathesis reaction is usually carried out in the presence of catalysts based on tungsten, molybdenum or ruthenium. However, as the tungsten-based and molybdenum-based catalysts are very sensitive to moisture, those based on ruthenium are preferred.
Among the ruthenium-based catalysts used for the polymerization of cycloolefins, we may notably mention those of formula (I):

where for example: X1=X2=Cl; R1=phenyl; R2=H; L1 and L2 denote a ligand of the unsaturated nitrogen-containing heterocyclic carbene type or NHC (for "N-Heterocyclic Carbene") of formula (II):

where Ra=Rb=isopropyl or cyclohexyl and Rc=Rd=H, as described in U.S. Pat. No. 7,652,145. Other catalysts of formula (I) but comprising phosphines, or a phosphine and a saturated NHC, as ligands L1 and L2, notably comprise the Nolan II catalyst of formula:

as well as the catalysts described in document WO 00/46255. The Grubbs catalysts of first and second generation, of formula:

and the catalyst C827, of formula:

are covered by this definition. Their use in the ring-opening metathesis of cycloolefins is also described in documents U.S. Pat. Nos. 5,342,909 and 6,476,167 (Grubbs I) as well as in U.S. Pat. No. 7,329,758 (Grubbs II and C827).
Moreover, there is a report (F. B. Hamad et al., Olefin Metathesis Ruthenium Catalysts Bearing Unsymmetrical Heterocyclic Carbenes, Coordination Chemistry Reviews (2013), dx.doi.org/10.1016/j.ccr.2013.04.015) of the use of several catalysts containing a ligand of the asymmetric NHC type in ring-opening metathesis reactions, in particular the complexes of formula:
which are considered to be more effective than the Grubbs I catalyst (but less effective than the Grubbs II catalyst) in the polymerization of cyclooctadiene and to have an activity similar to the complex containing a symmetric NHC ligand illustrated above.
Other catalysts comprising an asymmetric NHC ligand have been proposed as metathesis catalysts (WO 2014/091157). However, it has never yet been suggested to use them in the polymerization of cycloolefins by ring-opening metathesis.
The applicant found that the Grubbs II catalyst led to a material having a high compressive strength, which is important for a great many applications, but that it did not allow controlled polymerization of cycloolefins and so resulted in an inhomogeneous polymer material, with bubbles. The other complexes known to date as catalysts of ring-opening metathesis of cycloolefins do not have the same drawbacks, but the compressive strength of the materials obtained is inadequate. Furthermore, for some of these complexes an organic solvent, whose environmental impact we are seeking to reduce, has to be added to the reaction mixture. Moreover, incomplete dissolution of the catalyst in the reaction mixture also leads to an inhomogeneous material, having grains that are potential weak points for the material formed.
Therefore there is still need for a method of metathesis of cycloolefins that leads to a material having a better compromise of properties (surface appearance and compressive strength) than the ruthenium complexes known for this purpose.
It would also be useful to have a catalytic system allowing better control of polymerization than some of the catalysts of the prior art that lead to excessively rapid polymerization, leading to a large increase in the viscosity of the reaction mixture even before it is introduced into the mold, or before filling of the mold or else before the catalyst is properly dispersed in the resin. This control is particularly critical in the manufacture of large moldings.
It would moreover be useful to have a method of metathesis of cycloolefins that is more environmentally friendly, in the sense that it requires no, or less, organic solvent in the reaction mixture.

Method for the polymerization of cycloolefins by means of ring-opening metathesis


A sucking cover inserted into an electric connector with terminals received therein includes a sucking portion and an insertion portion. The sucking portion has a sucking surface at the front and a catching surface at the rear. A plane sucking area is formed as a portion of the sucking surface. The sucking surface is parallel with a bottom plate of the electric connector mounted on a PCB. The catching surface is against the top of the electric connector when the sucking cover is inserted into the electric connector. The inserted portion projected from the catching surface has an inserted wall and ribs. While the inserted portion is inserted into an inserted slot of the electric connector, the electric connector can be moved while the sucked cover is moved. In SMT, this action will improve the effective of the electric connector located in a PCB.

1. Field of the Invention
This present invention relates generally to a sucking cover used in the field of the printed circuit assemblies (PCA), and more particularly to a sucking cover sucking an electric connector which is bonded to a PCB by SMT (Surface Mount Technology).
2. The Related Art
The SMT is used in the electric assembly. While an element is inserted into a PCB and welded in the PCB, the element is sucked and drawn by a vacuum sucking apparatus to the PCB. If the surface of the element is not plane, the element will not be held by the vacuum sucking apparatus, so the element is not assembled in the PCB by SMT. If the element is located in the PCB by handwork, it is dangerous and inefficiency.


The symptoms of congenital heart failure are addressed in this surgical procedure for mounting a patch in the ventricle of the heart to reduce ventricular volume. Placement of the patch is facilitated by palpating a beating heart to identify akinetic, although normal appearing, tissue. An apical patch having an oval configuration facilitates return of the heart to a normal apical shape which enhances muscle fiber efficiency and a normal writhing pumping action. An inferior patch having a triangular configuration can also be used. The patches include a semi-rigid ring, and a circumferential rim to address bleeding. Patch placement is further enhanced by creating a Fontan-type neck and use of pledged sutures. Intraoperative vascularization and valve replacement is easily accommodated. Increased injection fraction, reduced muscle stress, improved myocardial protection, and ease of accurate patch placement are all achieved with this procedure.

1. Field of the Invention
This invention relates generally to surgical methods and apparatus for addressing ischemic cardiomyopathy, and more specifically to methods and apparatus for restoring the architecture and normal function of a mammalian heart.
2. Discussion of the Prior Art
The function of a heart in an animal is primarily to deliver life-supporting oxygenated blood to tissue throughout the body. This function is accomplished in four stages, each relating to a particular chamber of the heart. Initially deoxygenated blood is received in the right auricle of the heart. This deoxygenated blood is pumped by the right ventricle of the heart to the lungs where the blood is oxygenated. The oxygenated blood is initially received in the left auricle of the heart and ultimately pumped by the left ventricle of the heart throughout the body. It can be seen that the left ventricular chamber of the heart is of particular importance in this process as it is relied upon to pump the oxygenated blood initially through a mitral valve into and ultimately throughout the entire vascular system.
A certain percentage of the blood in the left ventricle is pumped during each stroke of the heart. This pumped percentage, commonly referred to as the ejection fraction, is normally about sixty percent. It can be seen that in a heart having a left ventricular volume such as seventy milliliters, an ejection fraction of sixty percent would deliver approximately 42 milliliters of blood into the aorta. A heart with reduced left ventricular volume might have an ejection fraction of only 40% and provide a stroke volume of only 28 millimeters.
Realizing that the heart is part of the body tissue, and the heart muscle also requires oxygenated blood, it can be appreciated that the normal function of the heart is greatly upset by clotting or closure of the coronary arteries. When the coronary arteries are blocked, an associate portion of the heart muscle becomes oxygen-starved and begins to die. This is clinically referred to as a heart attack. Ischemic cardiomyopathy typically occurs as the rest of the heart dilates in an attempt to maintain the heart's output to the body.
As the ischemic area loses its contraction, the area of dilatation is restricted to the remaining muscle. The three regions of typical infraction include, 1) the anterior wall septum and anterolateral wall which are supplied by the anterior descending coronary artery; 2) the septum and inferior wall supplied by the left anterior artery and the right coronary artery which narrows due to the heart's elliptical shape; and 3) the lateral wall supplied by the circumflex artery which perfuses the lateral wall including the papillary muscle attachments to the ventricular wall.
As the ischemic cardiomyopathy progresses, the various structures of the heart are progressively involved including the septum, the apex and the anterolateral wall of the left ventricle. Within a particular wall, the blood starvation begins at the inside of the wall and progresses to the outside of the wall. It can be seen that addressing ischemic cardiomyopathy shortly after the heart attack can limit the detrimental effects to certain elements of the heart structure, as well as the inner most thicknesses of the walls defining those structures.
As a heart muscle is denied blood nourishment support, its ability to participate, let alone aid, in the cardiac pumping function, is greatly diminished and typically nil. Such muscle is commonly referred to as akinetic, meaning it does not move. In some cases the wall will form elastic scar tissue which tends to balloon in response to the pumping action. This muscle tissue is not only akinetic, in that it does not contribute to the pumping function, but it is in fact dyskinetic, in that it detracts from the pumping function.
The akinetic tissue will, in addition to not contracting, cause cardiac enlargement due to dilatation or loss of its contractile capacity. The dilatation will widen, and thereby change the fiber orientation of the remaining muscle in the left ventricle. This will make the ventricle spherical, and change it from the normal elliptical form which optimizes contraction.
The shape of the ventricle is normally elliptical or conical with an apex that allows a 60 degree fiber orientation of the muscle. This orientation ensures efficient development of intramuscular torsion to facilitate the pumping of blood. Compression of the left ventricular cavity occurs by torsional defamation which thickens the left ventricular wall. This increases progressively from the mid-ventricular wall to the apex. As a result, maintenance of the apical anchor is a central theme of cardiac contraction.
Perhaps the most notable symptom of ischemic cardiomyopathy is the reduction in the ejection fraction which may diminish, for example, from a normal sixty percent to only twenty percent. This results clinically in fatigue, and inability to do stressful activities, that require an increase in output of blood from the heart. The normal response of the heart to a reduction in ejection fraction is to increase the size of the ventricle so that the reduced percentage continues to deliver the same amount of oxygenated blood to the body. By way of example, the volume of the left ventricle may double in size. Furthermore, a dilated heart will tend to change its architecture from the normal conical or apical shape, to a generally spherical shape. The output of blood at rest is kept normal, but the capacity to increase output of blood during stress (i.e., exercise, walking) is reduced. Of course, this change in architecture has a dramatic effect on wall thickness, radius, and stress on the heart wall. In particular, it will be noted that absent the normal conical shape, the twisting motion at the apex, which can account for as much as one half of the pumping action, is lost. As a consequence, the more spherical architecture must rely almost totally on the lateral squeezing action to pump blood. This lateral squeezing action is inefficient and very different from the more efficient twisting action of the heart. The change in architecture of the heart will also typically change the structure and ability of the mitral valve to perform its function in the pumping process. Valvular insufficiency can also occur due to dilatation.
A major determinant of both cardiac oxygen requirement and efficiency is based upon a formula where stress or pressure is multiplied by the radius and divided by twice the thickness of the cardiac wall. Increasing stress reduces contractility or rejecting capacity, and raises energy requirements in the remaining contracting muscle. As the shape changes from elliptical to spherical, wall stress increases thereby demanding higher energy from the remaining cardiac muscle. This dilation, which occurs anteriorly, effects the septum, apex and anterolateral wall. Thus, the normally oval apex becomes more spherical due to 1) a loss of infarcted muscle, and 2) dilation of the remaining contracting muscle.
With inferior coronary artery involvement, the inferior wall, septum, and apex are affected. These elements form, naturally a myocardial triangle, with a base adjacent to the mitral valve, and the septum and free lateral walls forming the planes going to the cardiac apex. As the triangle becomes widened, due to loss of contracting muscle after infraction, the same form of ventricular dilatation occurs. However, instead of making the oval ventricle into a sphere in the anterior segment, with subsequent enlargement (dilatation) of the non-infarcted remaining contracting muscle, there is an increase in the triangle inferiorly. As a result, there is an increase in both the transverse diameter as well as the longitudinal dimension. Thus, inferior coronary involvement results in dilatation of the entire inferior segment.
Although the dilated heart may be capable of sustaining life, it is significantly stressed and rapidly approaches a stage where it can no longer pump blood effectively. In this stage, commonly referred to as congestive heart failure, the heart becomes distended and is generally incapable of pumping blood returning from the lungs. This further results in lung congestion and fatigue. Congestive heart failure is a major cause of death and disability in the United States where approximately 400,000 cases occur annually.
Following coronary occlusion, successful acute reperfusion by thrombolysis, (clot dissolution) percutaneous angioplasty, or urgent surgery can decrease early mortality by reducing arrhythmias and cardiogenic shock. It is also known that addressing ischemic cardiomyopathy in the acute phase, for example with reperfusion, may salvage the epicardial surface. Although the myocardium may be rendered akinetic, at least it is not dyskinetic. Post-infarction surgical revascularization can be directed at remote viable muscle to reduce ischemia. However, it does not address the anatomical consequences of the akinetic region of the heart that is scarred. Despite these techniques for monitoring ischemia, cardiac dilation and subsequent heart failure continue to occur in approximately fifty percent of post-infarction patients discharged from the hospital.
The distribution of heart failure is more common with occlusion of the left anterior descending coronary artery (LAD) due to its perfusion of the apex. But, this can also occur with inferior infarction, especially if there is inadequate blood supply to the apex due to 1) prior damage to the left anterior descending artery, or 2) inadequate blood supply due to stenosis or poor function. In general, the distribution of ischemia is 45% anterior, 40% inferior, and 15% circumflex. However, the incidence of congestive heart failure is more common in the anterior infarction.
Various surgical approaches have been taken primarily to reduce the ventricular volume. This is also intended to increase the ejection fraction of the heart. In accordance with one procedure, viable muscle is removed from the heart in an attempt to merely reduce its volume. This procedure, which is typically accomplished on a beating heart, has been used for hearts that have not experienced coronary disease, but nevertheless, have dilated due to leaking heart valves. Other attempts have been made to remove the scarred portion of the heart and to close the resulting incision. This has also had the effect of reducing the ventricular volume.
In a further procedure, a round, circular patch has been proposed for placement typically in the lateral ventricular wall. Unfortunately, providing the patch with a circular shape has allowed the dilated heart to remain somewhat enlarged with a thin and over-stressed wall section. The exact placement of the patch has been visually determined using only a visual indication where the typically white scar tissue meets the typically red normal tissue. Location of the patch has been facilitated in a further procedure where a continuous suture has been placed around the ventricular wall to define a neck for receiving the patch. The neck has been formed in the white scar tissue rather than the soft viable muscle. This procedure has relied on cardioplegia methods to stop the beating of the heart and to aid in suture placement.
In the past, the patch has been provided with a fixed or semi-rigid wall which has prevented the muscle from becoming reduced to an apical anchor which facilitates the twisting motion. The patches have had a fixed planar configuration which have prevented the lateral muscle from coapting to form an apex.
These surgical procedures have been met with some success as the ejection fraction has been increased, for example, from twenty-four percent to forty-two percent. However, despite this level of success, little attention has been paid to myocardial protection, the potential for monitoring the writhing action associated with apical structure, or the preferred structure for the patch. Failure to protect the heart during restoration of the segment has increased hospital mortality, morbidity, and irreversibly damaged some normal muscle needed to maintain the heart's output.

Anterior and inferior segment ventricular restoration apparatus and method


Disclosed is an organic electroluminescent device (organic EL device) which can achieve high efficiency and long lifetime even when driven at low voltage. The organic El device comprises at least a light-emitting layer and an electron-transporting layer between an anode and a cathode facing each other. The electron-transporting layer consists of two layers, namely, a first electron-transporting layer and a second electron-transporting layer and the first electron-transporting layer and the second electron-transporting layer are arranged sequentially in this order from the light-emitting layer side to the cathode side. The first electron-transporting layer contains an indole derivative in which the ring nitrogen atom is substituted with an aromatic group and an aromatic ring is fused to the indole ring.

An organic EL device in the simplest structure is generally constituted of a light-emitting layer and a pair of counter electrodes sandwiching the light-emitting layer and functions by utilizing the following phenomenon. Upon application of an electrical field between the electrodes, electrons are injected from the cathode and holes are injected from the anode and they recombine in the light-emitting layer; the energy level after the recombination returns from the conduction band to the valence band with release of energy in the form of light.
In recent years, organic thin films have been used in the development of organic EL devices. In particular, in order to enhance the luminous efficiency, the kind of electrodes has been optimized for the purpose of improving the efficiency of injecting carriers from the electrodes and a device has been developed in which a hole-transporting layer composed of an aromatic diamine and a light-emitting/electron-transporting layer composed of 8-hydroxyquinoline aluminum complex (hereinafter referred to as Alq3) are disposed in thin film between the electrodes. This device has brought about a marked improvement in the luminous efficiency over the conventional devices utilizing single crystals of anthracene and the like and thereafter the developmental works of organic EL devices have been focused on commercial applications to high-performance flat panels featuring self-luminescence and high-speed response.
In another effort to enhance the luminous efficiency of the device, the use of phosphorescent materials in place of fluorescent materials is investigated. The aforementioned device comprising a hole-transporting layer composed of an aromatic diamine and a light-emitting layer composed of Alq3 and many other devices utilize fluorescence. The use of phosphorescence, that is, emission of light from the excited triplet state, is expected to enhance the luminous efficiency approximately three to four times that of the conventional devices utilizing fluorescence (emission of light from the excited singlet state). To achieve this objective, the use of coumarin derivatives and benzophenone derivatives in the light-emitting layer has been investigated, but these derivatives merely produced luminance at an extremely low level. Thereafter, europium complexes were tried in utilization of the excited triplet state, but they too failed to emit light at high efficiency. The studies on utilization of phosphorescence are mostly centered on the use of organic metal complexes such as the iridium complexes mentioned in patent document 1 as phosphorescent dopants.    Patent document 1: JP 2003-515897 A    Patent document 2: JP Hei 5-214333 A    Patent document 3: JP Hei 11-162650 A    Patent document 4: JP Hei 11-176578 A    Patent document 5: JP 2005-093425 A
Further, studies are under way on enhancement of the efficiency and elongation of lifetime by means of lowering the driving voltage of the device. For example, patent document 2 discloses the use of quinolinol-based metal complexes such as Alq3. Even so, organic EL devices using such compounds require high driving voltage and show a short lifetime and there is a growing demand for electron-transporting materials capable of lowering the driving voltage, enhancing the efficiency, and elongating the lifetime still further.
Further, patent documents 3 and 4 disclose indolocarbazole compounds, but the disclosure is concerned with compounds in which the indolocarbazole skeleton is not linked to an aromatic heterocyclic group. Moreover, the documents recommend the disclosed indolocarbazole compounds for use as hole-transporting materials and commend them for their stability, but the documents do not teach at all the use of the disclosed indolocarbazole compounds as electron-transporting materials.
Further, patent document 5 discloses a scheme for improvement of the characteristics of the device by dividing an electron-transporting layer into a first electron-transporting layer and a second electron-transporting layer and using a specified compound in each layer. According to the disclosure, the intended effect can be manifested provided that the ionization potential of the first electron-transporting layer (IP1) is related to the ionization potential of the second electron-transporting layer (IP2) as IP1<IP2.

This patent is subject to a terminal disclaimer.

Organic electroluminescent device comprising a first electron-transporting layer and a second electron-transporting layer

Nippon Steel & Sumikin Chemical Co., Ltd.


A white LED illumination device can include a white LED that has unevenness in tone and is used as a light source. The white LED illumination device can emit white light with high color rendering properties without unevenness in tone and can include the above noted white LED located adjacent an optical lens. The white LED and optical lens can be arranged so that the optical axes of both are substantially aligned with each other. The white LED can include an LED chip which emits light having a peak wavelength in the blue wavelength range and a fluorescent material which can be excited by the light emitted from the LED chip to emit yellow or yellowish green fluorescence (i.e., complementary colors to blue) by use of wavelength conversion. The optical lens can have a recessed light incident surface having an opening, a light emitting surface, and a totally reflective surface positioned between the light incident surface and the light emitting surface. The inner bottom of the recessed light incident surface can include a convex shape having a convex surface. The light emitting surface can be composed of a convex portion having a center and a periphery that can be formed in different shapes or curvatures, and can include a flat surface surrounding the convex portion.

This application claims the priority benefit under 35 U.S.C. § 119 of Japanese Patent Application No. 2005-334311 filed on Nov. 18, 2005, which is hereby incorporated in its entirety by reference.
1. Field
The disclosed subject matter relates to a white LED illumination device, and in particular, relates to a white LED illumination device having a white LED as a light source. The white LED has an LED chip and a wavelength conversion material. The LED chip can emit light having a peak wavelength in, for example, the blue wavelength range. The wavelength conversion material such as a fluorescent material is excited by the light from the LED chip and performs wavelength conversion to emit, for example, yellow or yellowish green fluorescence which is a complementary color of blue.
2. Brief Description of the Related Art
LED chips generally emit light that has steep spectral characteristics (spectral distribution). Humans typically recognize the light as light with a tone approximately corresponding to its peak wavelength λp (wavelength at which maximum emission intensity is achieved). Accordingly, the LED chip emits light in an intrinsic tone caused by the material, composition, structure, and the like of the LED chip. This emitted light is generally not white light (natural light) with superior color rendering properties like that produced by the sun (which includes a wavelength component in a wide wavelength range throughout the ultraviolet, visible, and infrared regions).
There are some methods to obtain white light by using the LED chip emitting light with such spectral characteristics as a light source. In one method, three kinds of LED chips, that is, an LED chip emitting red light (red LED chip), an LED chip emitting green light (green LED chip), and an LED chip emitting blue light (blue LED chip) are employed. They are turned on at the same time, and as a result, white (W) light with a desired tone can be generated by means of additive color mixture. The tone can be adjusted by independently controlling the respective amounts of red (R) light, green (G) light, and blue (B) light which are the three primary colors and are emitted by the respective LED chips.
This method has a disadvantage in that three driving circuits are necessary to independently control the respective amounts of light emitted by the LED chips. However, there is also an advantage in that the tone of light generated by means of the additive color mixture can be successively controlled.
Another method uses a fluorescent material serving as a wavelength conversion material. This method utilizes a principle in which when a fluorescent material is irradiated with light, the fluorescent material is excited and emits light with a longer wavelength than that of the excitation light.
Specifically, for example, the fluorescent material such as YAG, TAG, or orthosilicate is available. When blue light (light having a peak wavelength in the blue wavelength range) is emitted from an LED chip made of a semiconductor material such as ZnSe, InGaN, GaN, ZnO, etc., excites the fluorescent material, the fluorescent material emits, via wavelength conversion, yellow and/or yellowish green fluorescence which are complementary colors of the blue light. Yellow light, which is generated by wavelength conversion when part of the blue light emitted from the LED chip excites the fluorescent material, can be added to or mixed with part of the blue light emitted from the LED chip to generate white light by means of the additive color mixture.
In another example, when an LED chip emits blue light, a mixture of two kinds of fluorescent materials can be employed, which emit green and red fluorescence, respectively, by wavelength conversion when excited by the blue light. Green light and red light, which are generated by wavelength conversion when part of the blue light emitted from the LED chip excites the fluorescent materials can be mixed with or added to part of the blue light emitted from the LED chip to generate white light by means of additive color mixture.
When an LED chip emits ultraviolet light, a mixture of three kinds of fluorescent materials can be employed, which emit blue, green, and red fluorescence, respectively, by wavelength conversion when excited by the ultraviolet light. Blue light, green light, and red light, which are generated by wavelength conversion when part of the ultraviolet light emitted from the LED chip excites the fluorescent materials, can be mixed together and generate white light by means of additive color mixture.
Furthermore, when the wavelength of light emitted from an LED chip and a kind of fluorescent material are appropriately selected and combined, light in various tones other than white light can also be generated.
FIG. 1 is an example of such an LED. In this LED, part of the light emitted from a light source excites a fluorescent material for wavelength conversion and generates light different in tone from the light emitted from the light source. The LED has a printed circuit board 53 in which conductive patterns 52a and 52b are formed on an insulating substrate 51. A lamp house 56 is attached to the printed circuit board 53. The lamp house 56 is provided with a bowl-shaped recessed portion 55 having a reflective surface 54 opening upward and outward. A blue LED chip 58, which can emit blue light, is mounted on the conductive pattern 52a formed on an inner bottom 57 of the recessed portion 55 (on the printed circuit board 53) via a conductive adhesive 59 to electrically connect a lower side electrode of the blue LED chip 58 to the conductive pattern 52a. An upper side electrode of the blue LED chip 58 is electrically connected to the conductive pattern 52b through an overhead wired bonding wire 60. Furthermore, a transparent resin 62, into which a fluorescent material 61 is mixed, is filled into the recessed portion 55. The blue LED chip 58 and the bonding wire 60 are sealed by the resin to be shielded from air. In this instance, when the blue light excites the fluorescent material 61, the fluorescent material 61 can emit via wavelength conversion yellow or yellowish green fluorescence, which are complementary colors of blue.
In the LED 50 with such a structure, the light emitted from the blue LED chip 58 reaches a light emitting surface 63 through the transparent resin 62 into which the fluorescent material 61 is mixed. In this case, the optical path and optical path length of the light differ according to an emission direction of the light from the blue LED chip 58. To be more specific, when L1 represents light emitted from the blue LED chip 58 in an optical axis X direction (upward) of the blue LED chip 58 toward the light emitting surface 63, d1 represents its optical path length. L2 represents light emitted from the blue LED chip 58 in a slanting upward direction from the blue LED chip 58 toward the light emitting surface 63, and d2 represents its optical path length. L2 is longer than L1, and therefore, the difference of the optical paths is represented by d2-d1.
Such difference in the optical path means that there is difference in a ratio of wavelength conversion of the light from the blue LED chip 58 by the fluorescent material. In other words, the light L1 reaching the light emitting surface 63 through the short optical path has a blue tone because it is subjected to a low ratio of wavelength conversion by the fluorescent material. On the contrary, the light L2 reaching the light emitting surface 63 through the long optical path has a yellow tone because it is subjected to a high ratio of wavelength conversion by the fluorescent material.
Accordingly, this LED emits bluish white light in a front direction and emits yellowish white light in the slanting upward direction. Also, the bluish white light is emitted from the center of the light emitting surface of the LED and the yellowish white light is emitted from the periphery of the light emitting surface of the LED. Thus, the LED has an optical characteristic with an uneven tone because the emitted white light has different tones according to its emission direction and emission portion.
By the way, it is conventionally known that a light source that evenly emits light in every direction, like the above-described LED, is optically regarded as a point source of light. This is true when the size of the light source is much smaller than the distance from which it is observed (observation distance is approximately five times or more of the size of the light source).
Consider that an illumination device for illuminating a position that is approximately five times or more of the size of the light source away is configured using the above-described LED as a light source. In this case, it is necessary to secure the illuminance of an illumination surface and improve unevenness in the tone of the light source by applying certain light-gathering means to the wide directional light emitted from the light source.
To cope with this, as shown in FIG. 2, there is an LED in which a condenser lens is provided in front of the LED in a light emission direction to collect the light to an illumination surface and even the tone of illumination light in the illumination surface.
Bluish white light emitted in a front direction of an LED 80 is refracted by an upper incident surface 82 of a lens 81 and introduced into the lens 81 while collected. The bluish white light reaches a center emitting surface 83 after passing through the lens 81, and is refracted by and gathered at the center emitting surface 83, and is emitted to the outside of the lens 81. Yellowish white light emitted in a side direction of the LED 80, on the other hand, is refracted by a side incident surface 84 of the lens 81 and introduced into the lens 81. The yellowish white light reaches a peripheral reflective surface 85 after passing through the lens 81. The light reflected (totally reflected) by the peripheral reflective surface 85 reaches a peripheral emitting surface 86, provided on the periphery of the center emitting surface 83, after passing through the lens 81. Then, the yellowish white light is emitted to the outside of the lens 81 from the peripheral emitting surface 86. In this instance, the yellowish white light emitted in the side direction of the LED 80 and emitted to the outside from the peripheral emitting surface 86 is gathered at the center of an illumination region, and is mixed with the bluish white light, which is emitted in the front direction of the LED 80 and emitted to the outside from the center emitting surface 83. Therefore, it is possible to obtain white light in even tone (for example, please see Japanese Patent Laid-Open Publication No. 2005-216782 and U.S. Patent Publication No. 2005-179064, which are hereby incorporated in their entirety by reference).
The white light in the different tones emitted in the different directions of the LED 80 are mixed on the illumination surface and the unevenness in tone is resolved so that it is possible to obtain even white light. The white light in the different tones emitted from the different sections of the LED 80, however, are incident on the illumination surface as-is. In addition to this, they are magnified through an optical system in which the light emitting surface of the LED 80 is composed of the lens 81, so that the unevenness in tone is not resolved. As a result, white light with unevenness in tone is still emitted through the illumination surface.


A combination exhaust gas post treatment/muffler device in the exhaust gas section of an internal combustion engine is provided. The exhaust gas post treatment within the muffler, which forms sulfuric acid, takes place in at least one exhaust gas post treatment/muffler module, and only that housing thereof through which flows exhaust gas that is to be cleaned is produced from ferritic or austenitic stainless steel, thus making it possible to produce the outer walls of the muffler, as well as any inner element thereof, such as a transverse wall, that is disposed externally of the exhaust gas post treatment/muffler module of unalloyed sheet steel that is coated with aluminum or some other material.

The present invention relates to a combination exhaust gas post treatment/muffler device in the exhaust gas section of an internal combustion engine, especially a diesel engine of a commercial vehicle, such as a truck or bus, and including a muffler that is spatially delimited by a front and rear end wall as well as a peripheral outer wall, and in the interior of which is built in at least one preliminary oxidation catalytic converter, which significantly increases the NO2 amount in the exhaust gas that is flowing through, and at least one exhaust gas post treatment device, whereby exhaust gas that is to undergo post treatment can be introduced into the muffler via an inlet tube, and after flowing through the preliminary oxidation catalytic converter as well as the exhaust gas post treatment device can again be conveyed out of the muffler in a cleaned and indirectly muffled state.
Combination exhaust gas post treatment/muffler devices of the aforementioned type have been disclosed, for example, in the 23rd International Viennese Motor Symposium on the 25th and 26th of Apr. 2002 and have been documented in the Progress Reports, VDI series 12 Nr. 490, volume 2, Düsseldorf, VDI publication 2002, pages 196-216. In this connection, a system was introduced where four exhaust gas post treatment modules were disposed in a muffler for parallel flow therethrough, whereby each module, enclosed in a casing, is provided with a circular cylindrical preliminary oxidation catalytic converter and, following immediately coaxially a circular cylindrical particle separator having the same diameter.
Due to the use of sulfur-containing fuels, there results during the oxidation of the exhaust gas sulfuric acid that has a very corrosive effect within the exhaust gas post treatment/muffling system. This formation of corrosion caused by sulfuric acid is counteracted by the use of high-quality austenitic stainless steel materials during the manufacture of the exhaust gas post treatment and muffling devices. However, in comparison to structural steels these austenitic stainless steels are much more expensive, and require for the processing of appropriate semi-finished articles, such as sheets or plates, also considerably more complicated and expensive tools, which on the whole thus cause relatively high manufacturing costs for such systems that are resistant to sulfuric acid. In comparison to exhaust gas post treatment/muffling systems that require no configuration that is resistant to sulfuric acid, the system costs for an embodiment that is resistant to sulfuric acid increases by a factor of 3 to 5.
It is therefore an object of the present invention to provide exhaust gas post treatment/muffling devices of the aforementioned general type with structural features that provide the possibility of remedying the problem of corrosion caused by sulfuric acid in a cost-reducing manner.

Combination exhaust gas post treatment/muffler device in the exhaust gas section of an internal combustion engine


A mounting mechanism for coupling a compressor to an automobile engine including a mounting bracket, at least one flange projecting from the outer peripheral surface of the compressor and a fastener for fastening each flange to the mounting bracket. The mounting bracket includes a vibration absorbing coupling mechanism for coupling each fastener to the mounting bracket and absorbing vibration generated by the compressor. The vibration absorbing coupling mechanism comprises at least one vibration absorbing unit having its longitudinal axis in substanially parallel alignment with the longitudinal axis of the compressor, while being in substantially perpendicular alignment with the center line of at least one of the fasteners.

A compressor, which is used in an automobile air conditioning system, is usually mounted on the engine of the automobile through a suitable mounting bracket. Referring to FIGS. 1 and 2, a conventional mounting arrangement is shown which includes four flange portions 11 extending radially from the housing of compressor 10 and bracket 20. Bracket 20 includes base portion 201 for attachment to engine 40, and flange portions 202 extending radially outwardly from base portion 201 for attachment to compressor flanges 11. Base portion 201 has a plurality of holes 22 which are formed to align with threaded holes 41 formed on the end surface of engine 40. Bracket 20 also includes flange portions 202 having threaded holes 21 which are formed to align with holes 9 formed through compressor flange portions 11. Accordingly, bracket 20 may be coupled to engine 40 by inserting threaded bolts 31 through washers 23 and holes 22 and 41. In turn, compressor 10 may be coupled to bracket 20 by inserting threaded bolts 30 through spring washers 32, washers 33 and holes 9 and 21. Compressor 10 is thus mounted on engine 40 through bracket 20.
In such a mounting construction, compressor 10 and mounting bracket 20, both of which are formed of high strength material, are directly connected through a bolt mechanism. Mechanical vibration, and more specifically vibration in the axial direction, which is generated by the operation of compressor 10, is thus transmitted directly to engine 40, causing loud noise. This noise is then transmitted from the engine compartment to the passenger compartment of the automobile.

Vibration absorbing mounting mechanism for an automotive air conditioning compressor


A heat sink assembly for removing heat from an electronic device and comprising a base, a lid in spaced relationship with and parallel to the base, and an outer wall spiraling radially outwardly about an inlet axis from an inner exit position to an outer exit position to define a tangential outlet between said exit positions. Each of a plurality of curved fins presents a concave surface and a convex surface and extends from an inner circle with radius concentric with the inlet axis to an outer circle with radius concentric with the inlet axis to define a plurality of curved channels between adjacent fins for directing the flow of cooling fluid radially from the inlet axis. Each of the curved channels is disposed at a constant distance between next adjacent fins for a major length there along from the inner circle with radius toward the outer circle with radius. That substantially constant distance extends from the inner circle with radius to a perpendicular position where the convex surface of that fin is perpendicular to the intersection of the outer circle with radius with the next adjacent fin to the convex surface.

1. Field of the Invention
The subject invention relates to a cooling assembly for cooling an electronic device such as a microprocessor or a computer chip.
2. Description of the Prior Art
These electronic devices generate a high concentration of heat, typically a power density in the range of 5 to 35 W/cm2. Accordingly, research activities have focused on developing more efficient cooling assemblies capable of efficiently dissipating the heat generated from such electronic devices, while occupying a minimum of space.
A forced air-cooled assembly typically includes a heat exchanger and a heat sink, and cools the electronic device by natural or forced convection cooling methods. The electronic device is attached to the heat sink and transfers heat thereto. The heat exchanger typically uses air to directly remove the heat from the heat sink. However, air has a relatively low heat capacity. Such forced air-cooled assemblies are suitable for removing heat from relatively low power heat sources with a power density in the range of 5 to 15 W/cm2. However, the increased computing speeds have resulted in a corresponding increase in the power density of the electronic devices in the order of 20 to 35 W/cm2, thus requiring more effective cooling assemblies.
In response to the increased heat produced by the electronic devices, liquid-cooled cooling assemblies, commonly referred to as liquid cooled units ("LCUs") were developed. The LCUs employ a heat sink in conjunction with a high heat capacity cooling fluid, like water or water-glycol solutions, to remove heat from these types of higher power density heat sources. One type of LCU circulates the cooling fluid through the heat sink to remove the heat absorbed from the heat source affixed thereto. The cooling fluid is then transferred to a remote location where the heat is easily dissipated into a flowing air stream with the use of a liquid-to-air heat exchanger and an air-moving device such as a fan or a blower. These types of LCUs are characterized as indirect cooling units since they remove heat form the heat source indirectly by a secondary working fluid. Generally, a single-phase liquid first removes heat from the heat sink and then dissipates it into the air stream flowing through the remotely located liquid-to-air heat exchanger. Such LCUs are satisfactory for a moderate heat flux less than 35 to 45 W/cm2.
The LCUs of the prior art have included an axial inlet for coolant with a diverter to direct the coolant radially outward and into fins or vanes. Examples of such are illustrated in U.S. Pat. No. 4,733,293 to Gabuzda; U.S. Pat. No. 5,597,034 to Barker, III, et al.; U.S. Pat. No. 6,196,300 to Checchetti; U.S. Pat. No. 6,219,242 to Martinez and U.S. Pat. No. 6,719,038 to Bird et al. Each patent discloses a heat sink assembly having radial fins or vanes and used in a LCU. The heat sink assemblies include a base plate with a plurality of fins having smooth sidewalls extending upwardly from the base plate. In operation, the base plate absorbs the heat from the electronic device and transfers the heat to the fins. A cooling fluid flows past the smooth walled fins, drawing the heat from the fins, thereby removing the heat from the heat sink. The flow of cooling fluid is directed parallel to the fins by a central diverter.
The U.S. Pat. No. 5,019,880, issued to Higgins, discloses a heat sink that includes a circular base with a central flow diverter having a conical shape extending upwardly from the base. A plurality of planar fins is disposed radially about the circumference of the flow diverter and extends upwardly from the base to a lid. An inlet is disposed above the lid for directing a flow of cooling fluid axially onto the flow diverter. The flow of cooling fluid then circulates radially outward to the outer periphery of the base through a plurality of flow channels defined between the planar fins.

Impingement cooled heat sink with uniformly spaced curved channels


A device for the processing and separation of biological fluids into components comprises a hollow centrifugal processing chamber (10) fitted with an inlet/outlet head (20) and preferably with an axially movable piston (18). The inlet/outlet head has two separate inlets/outlets, for instance an axial inlet (29) and a lateral outlet (40). The processing chamber (1) is fitted with an internal flow guide (30) enabling operation of the device in a continuous processing mode wherein biological fluid to be processed is continuously intaken by say the axial inlet (29) and at the same time processed components are continuously removed via say the lateral outlet (40). The continuous processing flow can be driven by an external peristaltic pump (59) and/or by axial displacement of a piston (18) in the chamber (10).

The invention relates in particular to a device, a system and a method for the processing and separation of biological fluids into components of the type known from EP-B-0 912 250 and EP-B-1 144 026. Such known devices comprise a hollow centrifugal processing chamber rotatable about an axis of rotation. The processing chamber usually has an inner cylindrical wall enclosing a space for receiving biological fluids to be processed and having an inclined upper wall leading to a neck with an inlet/outlet for biological fluid to be processed and for processed components of the fluid. The space in the hollow processing chamber for receiving biological fluids occupies the entire volume across the hollow processing chamber between facing parts of the inner cylindrical wall and along the length of the cylindrical wall, said space having a given volume delimited by a bottom of the hollow cylindrical chamber, or a variable volume delimited by the position of an axially movable member within the cylindrical wall. The device also comprises a dynamic/static inlet/outlet head or "rotary seal" mounted on the neck of the processing chamber. The inlet/outlet head has a first part rotatable with the processing chamber and a second part that remains stationary. The first and second parts of the inlet/outlet head have a sealing means allowing rotation of the first part relative to the second part. The inlet/outlet head has a central through-passage for the inlet of biological fluid to be processed and the outlet of processed/separated components of the fluid.
Typically the centrifugal processing chamber contains within its cylindrical wall an axially movable member such as a piston that defines a separation space of variable volume wherein the biological fluid to be processed and separated is received. By axially moving this member, biological fluids can be intaken or output.
This known device forms part of a system wherein the processing chamber is part of a disposable set comprising a plurality of containers for receiving on the one hand the biological fluid to be processed and separated and, on the other hand, the separated components, and optionally one or more additional containers for additive solutions.
The known device and system are suitable for processing and separating many types of biological fluids including whole blood, apheresis blood, bone marrow blood and expanded cells or stein cells. However, the quantity of biological fluid that can be processed/separated at one time is limited by the maximum volume of the processing chamber's separation space. Therefore, in order to process large volumes of biological fluids with this known device and system, it is necessary to resort to using multiple disposable sets one after another in a single apparatus, or to run several disposable sets in parallel in multiprocessing apparatus.
Other devices for processing and separating biological fluids are known, but their structure is incompatible with that of EP-B-1 144 026 and they do not achieve the same advantages as EP-B-1 144 026. For example WO 2012/137086 describes a blood centrifugal device with a rotatable inner bowl disposed within a rotatable housing defining therebetween a narrow gap for receiving the blood being processed. A stationary structure is disposed in a central recess along the central axis of the device for delivering blood from an inlet at the top to the bottom where it passes into the bottom end of the narrow gap. At the top of the gap a separator separates blood components.

Device, system and method for the continuous processing and separation of biological fluids into components