There are provided novel compounds of formula (I), wherein R1, R2, X, Y, V, W and Z are as defined in the specification, and pharmaceutically acceptable salts thereof, and enantiomers and racemates thereof; together with processes for their preparation, compositions containing them and their use in therapy. The compounds are inhibitors of nitric oxide synthase and are thereby particularly useful in the treatment or prophylaxis of inflammatory disease and pain.

The present invention relates to novel phenylheteroalkylamine derivatives, processes for their preparation, compositions containing them and their use in therapy.
Nitric oxide is produced in mammalian cells from L-arginine by the action of specific nitric oxide synthases (NOSs). These enzymes fall into two distinct classesxe2x80x94constitutive NOS (cNOS) and inducible NOS (iNOS). At the present time, two constitutive NOSs and one inducible NOS have been identified. Of the constitutive NOSs, an endothelial enzyme (ecNOS) is involved with smooth muscle relaxation and the regulation of blood pressure and blood flow, whereas the neuronal enzyme (ncNOS) serves as a neurotransmitter and appears to be involved in the regulation of various biological functions such as cerebral ischaemia. Inducible NOS has been particularly implicated in the pathogenesis of inflammatory diseases. Regulation of these enzymes should therefore offer considerable potential in the treatment of a wide variety of disease states (J. E. Macdonald, Ann. Rep. Med. Chem., 1996, 31, 221-230).
Considerable effort has been expended in efforts to identify compounds that act as specific inhibitors of one or more isoforms of the enzyme nitric oxide synthase. The use of such compounds in therapy has also been widely claimed.
According to the present invention, there is provided a compound of formula (I)
wherein:
X and Y independently represent C1 to 4 alkyl, C1 to 4 alkoxy, halogen, CF3, OCF3, CN, Cxe2x89xa1CH, S(O)mCH3, S(O)pCF3, NO2 or NHCHO;
m and p independently represent an integer 0, 1 or 2;
Z represents H or fluoro;
V represents O, S(O)n or NR3;
W represents C1 to 4 alkyl, C2 to 4 alkenyl, C2 to 4 alkynyl, C3 to 6 cycloalkyl or a 4 to 8 membered saturated heterocyclic ring incorporating one heteroatom selected from O, S and N; any of said groups being optionally further substituted by C1 to 4 alkyl, C1 to 4 alkoxy, C1 to 4 alkylthio, C3 to 6 cycloalkyl; halogen or phenyl; said phenyl group being optionally further substituted by one or more substituents selected independently from halogen, C1 to 4 alkyl, C1 to 4 alkoxy, CF3, OCF3, CN or NO2;
or W represents phenyl or a five or six membered aromatic heterocyclic ring containing 1 to 3 heteroatoms independently selected from O, S and N; said phenyl or aromatic heterocyclic ring being optionally substituted by one or more substituents selected independently from halogen, C1 to 4 alkyl, C1 to 4 alkoxy, OH, CN, NO2 or NR4R5; said alkyl or alkoxy group being optionally further substituted by one or more fluorine atoms;
R1 and R2 independently represent H, C1 to 4 alkyl or C3 to 6 cycloalkyl; said alkyl group being optionally substituted by C1 to 4 alkoxy, halogen, hydroxy, NR6R7, phenyl or a five or six membered aromatic or saturated heterocyclic ring containing 1 to 3 heteroatoms independently selected from O, S and N; said phenyl or aromatic heterocyclic ring being optionally further substituted by halogen, C1 to 4 alkyl, C1 to 4 alkoxy, CF3, OCF3, CN or NO2;
or the group NR1R2 together represents a 4 to 8 membered saturated azacyclic ring optionally incorporating one further heteroatom selected from O, S or NR8; said ring being optionally substituted by C1 to 4 alkyl, C1 to 4 alkoxy or OH; said alkyl group being optionally substituted by C1 to 4 alkoxy, OH or NR9R10;
or the group NR1 R2 together represents part of a five membered aromatic azacyclic ring optionally incorporating one further N atom;
R3 represents H or C1 to 4 alkyl;
R4, R5, R6, R7, R9 and R10 independently represent H or C1 to 4 alkyl;
R8 represents H or C1 to 6 alkyl; said alkyl group being optionally substituted by C1 to 4 alkoxy, OH, NR11R12, phenyl or a five or six membered aromatic or saturated heterocyclic ring containing 1 to 3 heteroatoms independently selected from O, S and N; said phenyl or aromatic heterocyclic ring being optionally further substituted by halogen, C1 to 4 alkyl, C1 to 4 alkoxy, CF3, OCF3, CN or NO2;
R11 and R12 independently represent H or C1 to 4 alkyl;
n represents an integer 0, 1 or 2;
or a pharmaceutically acceptable salt, enantiomer or racemate thereof.
The compounds of formula (I) and their pharmaceutically acceptable salts, enantiomers and racemates have the advantage that they are inhibitors of the enzyme nitric oxide synthase (NOS). In particular, the compounds of formula (I) and their pharmaceutically acceptable salts, enantiomers and racemates have the advantage that they are inhibitors of the inducible isoform of the enzyme nitric oxide synthase (iNOS).
The invention further provides a process for the preparation of compounds of formula (I) or a pharmaceutically acceptable salt, enantiomer or racemate thereof.
According to the invention there is also provided a compound of formula (I), or a pharmaceutically acceptable salt, enantiomer or racemate thereof, for use as a medicament.
Another aspect of the invention provides the use of a compound of formula (I) or a pharmaceutically acceptable salt, enantiomer or racemate thereof, in the manufacture of a medicament, for the treatment or prophylaxis of diseases or conditions in which inhibition of nitric oxide synthase activity is beneficial.
A more particular aspect of the invention provides the use of a compound of formula (I) or a pharmaceutically acceptable salt, enantiomer or racemate thereof, in the manufacture of a medicament, for the treatment or prophylaxis of inflammatory disease.
According to the invention, there is also provided a method of treating, or reducing the risk of, diseases or conditions in which inhibition of nitric oxide synthase activity is beneficial which comprises administering to a person suffering from or at risk of, said disease or condition, a therapeutically effective amount of a compound of formula (I) or a pharmaceutically acceptable salt, enantiomer or racemate thereof.
More particularly, there is also provided a method of treating, or reducing the risk of, inflammatory disease in a person suffering from or at risk of, said disease, wherein the method comprises administering to the person a therapeutically effective amount of a compound of formula (I) or a pharmaceutically acceptable salt, enantiomer or racemate thereof.
The compounds of the present invention may also be used advantageously in combination with a second pharmaceutically active substance, particularly in combination with a selective inhibitor of the inducible isoform of cyclooxygenase (COX-2). Thus, in a further aspect of the invention there is provided the use of a compound of formula (I) or a pharmaceutically acceptable salt, enantiomer or racemate thereof, in combination with a COX-2 inhibitor for the treatment of inflammation, inflammatory disease and inflammatory related disorders. And there is also provided a method of treating, or reducing the risk of, inflammation, inflammatory disease and inflammatory related disorders in a person suffering from or at risk of, said disease or condition, wherein the method comprises administering to the person a therapeutically effective amount of a compound of formula (I) or a pharmaceutically acceptable salt, enantiomer or racemate thereof in combination with a COX-2 inhibitor.
In one preferred embodiment, V represents O. In another preferred embodiment, V represents S.
In another preferred embodiment, X and Y independently represent Br, Cl, CH3, CF3 or CN. It is particularly preferred that X represents Cl or CF3. It is also particularly preferred that Y represents Cl, CN or CF3.
Preferably, W represents an optionally substituted five or six membered aromatic heterocyclic ring containing 1 to 3 heteroatoms independently selected from O, S and N. Particular examples are those wherein W represents thienyl, furyl, imidazolyl, pyridyl, thiazolyl or triazolyl.
Preferably, R1 and R2 independently represent H or C1 to 4 alkyl optionally substituted by C1 to 4 alkoxy or hydroxy. More preferably, R1 and R2 independently represent H or methyl.
Particular compounds of the invention include:
4-chloro-2-[[(1R)-4-(methylamino)-1-phenylbutyl]oxy]benzonitrile;
R-xcex3-(2,5-dichlorophenoxy)-N-methyl-benzenebutanamine;
4-chloro-2-[[(1R)-1-phenyl-4-(1-pyrrolidinyl)butyl]oxy]-benzonitrile;
4-chloro-2-[[(1R)-4-(4-morpholinyl)-1-phenylbutyl]oxy]-benzonitrile;
4-chloro-2-[[(1R)-4-[ethyl(2-hydroxyethyl)amino]-1-phenylbutyl]oxy]-benzonitrile;
4-chloro-2-[[(1R)-1-phenyl-4-[(3-pyridinylmethyl)amino]butyl]oxy]-benzonitrile;
4-chloro-2-[[(1R)-4-[[2-(1H-imidazol-5-yl)ethyl]amino]-1-phenylbutyl]oxy]-benzonitrile;
4-chloro-2-[[(1R)-4-(1H-imidazol-1-yl)-1-phenylbutyl]oxy]-benzonitrile;
4-chloro-2-[[(1R)-4-[(2-hydroxyethyl)amino]-1-phenylbutyl]oxy]-benzonitrile;
4-chloro-2-[[(1R)-4-(cyclopropylamino)-1-phenylbutyl]oxy]-benzonitrile;
4-chloro-2-[[(1R)-4-[(3-hydroxypropyl)amino]-1-phenylbutyl]oxy]-benzonitrile;
4-chloro-2-[[(1R)-4-[[(1R)-2-hydroxy-1-methylethyl]amino]-1-phenylbutyl]oxy]-benzonitrile;
4-chloro-2-[[(1R)-4-[[(1S)-2-hydroxy-1-methylethyl]amino]-1-phenylbutyl]oxo]-benzonitrile;
4-chloro-2-[4-[[(2-fluoroethyl)amino]-1-phenylbutyl]oxy]-benzonitrile;
R-xcex4-(2,5-dichlorophenoxy)-4-fluoro-N-methyl-benzenebutanamine;
S-xcex4-(2,5-dichlorophenoxy)-4-fluoro-N-methyl-benzenebutanamine;
R-xcex3-(2,5-dichlorophenoxy)-N,4-dimethyl-benzenebutanamine;
S-xcex3-(2,5-dichlorophenoxy)-N,4-dimethyl-benzenebutanamine;
xcex4-(2,5-dichlorophenoxy)-N-methyl-2-thiophenebutanamine;
2-[(4-amino-1-phenylbutyl)amino]-4-chloro-benzonitrile;
2-[[1-(3-aminopropyl)-3-methylbutyl]amino]-4-(trifluoromethyl) benzonitrile;
2-[[4-(2,5-dichlorophenoxy)-4-phenylbutyl]methylamino]ethanol;
1-[4-(2,5-dichlorophenoxy)-4-phenylbutyl]-4-piperidinol;
1-[4-(2,5-dichlorophenoxy)-4-phenylbutyl]piperazine;
1-[4-(2,5-dichlorophenoxy)-4-(2-thienyl)butyl]4-methyl-piperazine;
4-chloro-2-[4-(methylamino)-1-(3-thienyl)butoxy]-benzonitrile;
4-chloro-2-[1-(3-furanyl)-4-(methylamino)butoxy]benzonitrile;
2-[4-amino-1-(3-furanyl)butoxy]-4-chlorobenzonitrile;
4-chloro-2-[1-(2-furanyl)-4-(methylamino)butoxy]benzonitrile;
2-[[(1R)-4-amino-1-(1-methyl-1H-imidazol-2-yl)butyl]oxy]-4-chloro-5-fluorobenzonitrile;
4-chloro-2-[4-(methylamino)-1-(2-pyridinyl)butoxy]benzonitrile;
4-chloro-5-fluoro-2-[4-(methylamino)-1-(2-pyridinyl)butoxy]benzonitrile;
4-chloro-2-[4-(ethylamino)-1-(2-pyridinyl)butoxy]benzonitrile;
2-[4-amino-1-(3-pyridinyl)butoxy]-4-chloro-benzonitrile;
4-chloro-2-[4-(methylamino)-1-(3-pyridinyl)butoxy]-benzonitrile;
4-chloro-2-[4-(ethylamino)-1-(4-pyridinyl)butoxy]-benzonitrile;
4-chloro-2-[4-(methylamino)-1-(4-pyridinyl)butoxy]benzonitrile;
4-chloro-2-[4-[(2-hydroxyethyl)amino]-1-(4-pyridinyl)butoxy]benzonitrile;
2-[4-amino-1-(2-methoxy-3-pyridinyl)butoxy]-4-chloro-benzonitrile;
2-[4-amino-1-(1,2-dihydro-2-oxo-3-pyridinyl)butoxy]-4-chlorobenzonitrile;
2-[[(1R)-4-amino-1-(3-furanyl)butyl]oxy]-4-chloro-5-fluoro-benzonitrile;
4-chloro-5-fluoro-2-[[(1R)-1-(3-furanyl)-4-(methylamino)butyl]oxy]benzonitrile;
2-[4-amino-1-(2-thiazolyl)butoxy]-4-chlorobenzonitrile;
xcex4-[2-chloro-5-(trifluoromethyl)phenoxy]-2-thiazolebutanamine;
2-[4-amino-1-(1-methyl-1H-1,2,4-triazole-5-yl)butoxy-4-chlorobenzonitrile;
xcex4-[2-chloro-5-(trifluoromethyl)phenoxy]-1-methyl-1H-1,2,4-triazole-5-butanamine;
and pharmaceutically acceptable salts, enantiomers or racemates thereof.
Unless otherwise indicated, the term xe2x80x9cC1 to 4 alkylxe2x80x9d referred to herein denotes a straight or branched chain alkyl group having from 1 to 4 carbon atoms. Examples of such groups include methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl and t-butyl.
The term xe2x80x9cC1 to 6 alkylxe2x80x9d is to be interpreted analogously.
Unless otherwise indicated, the term xe2x80x9cC3 to 6 cycloalkylxe2x80x9d referred to herein denotes a cycloalkyl group having from 3 to 6 carbon atoms. Examples of such groups include cyclopropyl, cyclopentyl and cyclohexyl.
Unless otherwise indicated, the term xe2x80x9cC2 to 4 alkenylxe2x80x9d referred to herein denotes a straight or branched chain alkyl group having from 2 to 4 carbon atoms incorporating at least one carbon-carbon double bond. Examples of such groups include ethenyl, propenyl and butenyl.
Unless otherwise indicated, the term xe2x80x9cC2 to 4 alkynylxe2x80x9d referred to herein denotes a straight or branched chain alkyl group having from 2 to 4 carbon atoms incorporating at least one carbon-carbon triple bond. Examples of such groups include ethynyl, propynyl, and butynyl.
Unless otherwise indicated, the term xe2x80x9cC1 to 4 alkoxyxe2x80x9d referred to herein denotes a straight or branched chain alkoxy group having from 1 to 4 carbon atoms. Examples of such groups include methoxy, ethoxy, n-propoxy, i-propoxy and t-butoxy.
The term xe2x80x9cC1 to 4 alkylthioxe2x80x9d is to be interpreted analogously.
Unless otherwise indicated, the term xe2x80x9chalogenxe2x80x9d referred to herein denotes fluoro, chloro, bromo and iodo.
Examples of a 4 to 8 membered saturated azacyclic ring optionally incorporating one further heteroatom selected from O, S or N include pyrrolidine, piperidine, piperazine, morpholine and perhydroazepine.
Examples of a 4 to 8 membered saturated heterocyclic ring incorporating one heteroatom selected from O, S or N include pyrrolidine, piperidine, tetrahydrofuran and perhydroazepine.
Examples of a five or six membered aromatic heterocyclic ring containing 1 to 3 heteroatoms independently selected from O, S and N include furan, thiophene, pyridine, thiazole, imidazole, oxazole, triazole, oxadiazole, thiadiazole and pyrimidine.
Examples of a five or six membered saturated heterocyclic ring containing 1 to 3 heteroatoms independently selected from O, S and N include pyrrolidine, tetrahydrofuran, piperidine and piperazine.
Examples of a xe2x80x9cC1 to 4 alkyl or C1 to 4 alkoxy optionally further substituted by one or more fluorine atomsxe2x80x9d include CF3, CF3CF2, CF3CH2, CH2FCH2, CH3CF2, CF3CH2CH2, OCF3 and OCH2CF3.
Examples of a five membered aromatic azacyclic ring optionally incorporating one further N atom include pyrrole and imidazole.
According to the invention, we further provide a process for the preparation of compounds of formula (I), or a pharmaceutically acceptable salt, enantiomer or racemate thereof which comprises:
(a) reaction of a compound of formula (II)
wherein X, Y, V and Z are as defined in formula (I), with a compound of formula (III)
wherein W, R1 and R2 are as defined in formula (I); or
(b) reaction of a compound of formula (IV)
wherein X, Y and Z are as defined in formula (I) and L1 represents a leaving group, with a compound of formula (V)
wherein R1, R2, V and W are as defined in formula (I); or
(c) reaction of a compound of formula (VI)
wherein X, Y, V, W and Z are as defined in formula (I) and L2 is a leaving group, with a compound of formula (VII)
HNR1R2xe2x80x83xe2x80x83(VII)
wherein R1 and R2 are as defined in formula (I); or
(d) reaction of a compound of formula (II)
wherein X, Y, V and Z are as defined in formula (I), with a compound of formula (VIII)
wherein R1, R2 and W are as defined in formula (I) and L3 is a leaving group; or
(e) reduction of a compound of formula (IX)
wherein X, Y, V, W and Z are as defined in formula (I) and G represents a group that upon reduction is converted into a group NR1R2; and where necessary converting the resultant compound of formula (I), or another salt thereof, into a pharmaceutically acceptable salt thereof; or converting the resultant compound of formula (I) into a further compound of formula (I); and where desired converting the is resultant compound of formula (I) into an optical isomer thereof.
In process (a), the reactants (II) and (III) are coupled together in a suitable inert solvent such as tetrahydrofuran using, for example, Mitsunobu conditions. Thus, for example, the reactants are treated with a phosphine derivative and an azo derivative at a suitable temperature, generally between 0xc2x0 C. and the boiling point of the solvent. Suitable phosphine derivatives include triphenylphosphine and tributylphosphine. Suitable azo derivatives include diethyl azodicarboxylate, diisopropyl azodicarboxylate and 1,1xe2x80x2-(azodicarbonyl)dipiperidine.
In process (b), the reaction is performed by treating a nucleophile of formula (V) with an electrophile of formula (IV) in an inert solvent. Suitable leaving groups L1 include halides, particularly fluoride. The reaction is generally performed in the presence of a non-nucleophilic base such as sodium hydride. Suitable organic solvents are those such as N-methyl-2-pyrrolidinone, tetrahydrofuran and dimethylsulfoxide. The reaction is generally conducted at a temperature between 0xc2x0 C. and the boiling point of the solvent.
Alternatively, in process (b), the reaction will take place using an appropriate palladium source such as palladium (II) acetate in the presence of a suitable phosphine ligand such as BINAP.
In process (c), the amination reaction is performed by reacting a compound of formula (VI) with an amine (VII) in an inert solvent. Suitable leaving groups L2 include sulfonate, trifluorosulfonate, tosylate and halides selected from the group chloride, bromide or iodide. The nucleophile can be a primary or secondary amine in the presence of a base. This base can be either an excess of the amine nucleophile or can be an additive to the reaction mixture. Potential basic additives are metal carbonate, especially alkali metal carbonates, metal oxides and hydroxides, and tertiary amine bases. Suitable organic solvents are those such as acetonitrile, dioxane, N,N-dimethylformamide, N-methyl-2-pyrrolidinone, tetrahydrofuran, dimethylsulfoxide, sulfolane and C1 to 4 alcohols.
In process (d), the reaction is performed by treating a nucleophile of formula (II) with an. electrophile of formula (VIII) in an inert solvent. Suitable leaving groups L3 include halides, particularly chloride or bromide. The reaction is generally performed in the presence of a non-nucleophilic base such as sodium hydride. Suitable organic solvents are those such as N-methyl-2-pyrrolidinone, tetrahydrofuran and dimethylsulfoxide. The reaction is generally conducted at a temperature between 0xc2x0 C. and the boiling point of the solvent.
In process (e), G preferably represents an azido (N3) group. The required reduction may then be achieved by treating a compound of formula (IX) with a suitable reducing agent such as Sn(II) or triphenylphosphine. Preferably the reducing agent is triphenylphosphine and the reduction is carried out in a suitable inert solvent such as tetrahydrofuran.
It will be apparent to a person skilled in the art that in the above processes it may be desirable or necessary to protect an amine, hydroxyl or other potentially reactive group. Suitable protecting groups and details of processes for adding and removing such groups may be found by reference to the standard text xe2x80x9cProtecting Groups in Organic Synthesisxe2x80x9d, 2nd Edition (1991) by Greene and Wuts. In one preferred embodiment, amine groups are protected as carbamate derivatives, for example, as t-butyloxycarbamates. Thus, compounds of formula (I) in which R1 is H are conveniently prepared by removal of a carbamate protecting group from a corresponding compound of formula (I) wherein R1 is a carbamate group, especially a t-butyloxycarbamate group. Removal of the carbamate group is conveniently effected using hydrogen chloride in dioxan.
The present invention includes compounds of formula (I) in the form of salts, in particular acid addition salts. Suitable salts include those formed with both organic and inorganic acids. Such acid addition salts will normally be pharmaceutically acceptable although salts of non-pharmaceutically acceptable acids may be of utility in the preparation and purification of the compound in question. Thus, preferred salts include those formed from hydrochloric, hydrobromic, sulphuric, phosphoric, citric, tartaric, lactic, pyruvic, acetic, succinic, fumaric, maleic, methanesulphonic and benzenesulphonic acids.
Salts of compounds of formula (I) may be formed by reacting the free base, or a salt, enantiomer or racemate thereof, with one or more equivalents of the appropriate acid. The reaction may be carried out in a solvent or medium in which the salt is insoluble or in a solvent in which the salt is soluble, for example, water, dioxane, ethanol, tetrahydrofuran or diethyl ether, or a mixture of solvents, which may be removed in vacuo or by freeze drying. The reaction may also be a metathetical process or it may be carried out on an ion exchange resin.
Certain novel intermediates of formulae (III), (V), (VI), (VIII) and (IX) form another aspect of the invention.
Compounds of formula (III) may be prepared by reaction of a compound of formula (X)
wherein R1 and R2 are as defined in formula (I), with an organometallic derivative, Wxe2x80x94M, wherein W is as defined in formula (I) and M represents a metallic residue such as lithium or magnesium-halide, or M represents a silyl residue such as SiMe3.
Compounds of formula (IX) may be prepared by:
(a) reacting a compound of formula (II), as defined above, with a compound of formula (XI)
wherein W and G are as defined above; or
(b) reacting a compound of formula (IV), as defined above, with a compound of formula (XII)
wherein V, W and G are as defined above.
Compounds of formulae (II), (IV), (VII), (X), (XI) and (XII) are either known or may be prepared using known methods. Some such methods are illustrated within the Examples that are included herein. Other suitable methods will be readily apparent to the man skilled in the art.
Intermediate compounds may be used as such or in protected form. Protecting groups and details of processes for their removal may be found by reference to the standard text xe2x80x9cProtecting Groups in Organic Synthesisxe2x80x9d, 2nd Edition (1991) by Greene and Wuts.
The compounds of the invention and intermediates thereto may be isolated from their reaction mixtures and, if necessary further purified, by using standard techniques.
The compounds of formula I may exist in enantiomeric forms. Therefore, all enantiomers, diastereomers, racemates and mixtures thereof are included within the scope of the invention. The various optical isomers may be isolated by separation of a racemic mixture of the compounds using conventional techniques, for example, fractional crystallisation, or HPLC.
Intermediate compounds may also exist in enantiomeric forms and may be used as purified enantiomers, diastereomers, racemates or mixtures.
The compounds of formula (I), and their pharmaceutically acceptable salts, enantiomers and racemates, are useful because they possess pharmacological activity in animals. In particular, the compounds are active as inhibitors of the enzyme nitric oxide synthase. More particularly, they are inhibitors of the inducible isoform of the enzyme nitric oxide synthase and as such are predicted to be useful in therapy, for example, as anti-inflammatory agents. They may also have utility as inhibitors of the neuronal isoform of the enzyme nitric oxide synthase.
The compounds and their pharmaceutically acceptable salts, enantiomers and racemates are indicated for use in the treatment or prophylaxis of diseases or conditions in which synthesis or oversynthesis of nitric oxide synthase forms a contributory part. In particular, the compounds are indicated for use in the treatment of inflammatory conditions in mammals including man.
Conditions that may be specifically mentioned are:
osteoarthritis, rheumatoid arthritis, rheumatoid spondylitis, gouty arthritis and other arthritic conditions, inflamed joints;
eczema, psoriasis, dermatitis or other inflammatory skin conditions such as sunburn;
inflammatory eye conditions including uveitis, glaucoma and conjunctivitis;
lung disorders in which inflammation is involved, for example, asthma, bronchitis, chronic obstructive pulmonary disease, pigeon fancier""s disease, farmer""s lung, acute respiratory distress syndrome;
bacteraemia, endotoxaemia (septic shock), aphthous ulcers, gingivitis, pyresis, pain, meningitis and pancreatitis;
conditions of the gastrointestinal tract including inflammatory bowel disease, Crohn""s disease, atrophic gastritis, gastritis varialoforme, ulcerative colitis, coeliac disease, regional ileitis, peptic ulceration, irritable bowel syndrome, reflux oesophagitis, damage to the gastrointestinal tract resulting from infections by, for example, Helicobacter pylori, or from treatments with non-steroidal anti-inflammatory drugs;
and other conditions associated with inflammation.
The compounds will also be useful in the treatment and alleviation of acute pain or persistent inflammatory pain or neuropathic pain or pain of a central origin.
We are particularly interested in the conditions inflammatory bowel disease, rheumatoid arthritis, osteoarthritis, chronic obstructive pulmonary disease and pain.
The compounds of formula (I) and their pharmaceutically acceptable salts, enantiomers and racemates may also be useful in the treatment or prophylaxis of diseases or conditions in addition to those mentioned above. For example, the compounds may be useful in the treatment of atherosclerosis, cystic fibrosis, hypotension associated with septic and/or toxic shock, in the treatment of dysfunction of the immune system, as an adjuvant to short-term immunosuppression in organ transplant therapy, in the control of onset of diabetes, in the maintenance of pancreatic function in diabetes, in the treatment of vascular complications associated with diabetes and in co-therapy with cytokines, for example TNF or interleukins.
The compounds of formula (I) may also be useful in the treatment of hypoxia, for example in cases of cardiac arrest and stroke, neurodegenerative disorders including nerve degeneration and/or nerve necrosis in disorders such as ischaemia, hypoxia, hypoglycaemia, epilepsy, and in external wounds (such as spinal cord and head injury), hyperbaric oxygen convulsions and toxicity, dementia, for example pre-senile dementia, Alzheimer""s disease and AIDS-related dementia, Sydenham""s chorea, Parkinson""s disease, Tourette""s Syndrome, Huntington""s disease, Amyotrophic Lateral Sclerosis, Multiple Sclerosis, Korsakoff""s disease, imbecility relating to a cerebral vessel disorder, sleeping disorders, schizophrenia, depression, pain, autism, seasonal affective disorder, jet-lag, depression or other symptoms associated with Premenstrual Syndrome (PMS), anxiety and septic shock. Compounds of formula (I) may also be expected to show activity in the prevention and reversal of drug addiction or tolerance such as tolerance to opiates and diazepines, treatment of drug addiction, treatment of migraine and other vascular headaches, neurogenic inflammation, in the treatment of gastrointestinal motility disorders, cancer and in the induction of labour.
We are particularly interested in the conditions stroke, Alzheimer""s disease, Parkinson""s disease, multiple sclerosis, schizophrenia, migraine, cancer, septic shock and pain.
Prophylaxis is expected to be particularly relevant to the treatment of persons who have suffered a previous episode of, or are otherwise considered to be at increased risk of, the disease or condition in question. Persons at risk of developing a particular disease or condition generally include those having a family history of the disease or condition, or those who have been identified by genetic testing or screening to be particularly susceptible to developing the disease or condition.
For the above mentioned therapeutic indications, the dosage administered will, of course, vary with the compound employed, the mode of administration and the treatment desired. However, in general, satisfactory results are obtained when the compounds are administered at a dosage of the solid form of between 1 mg and 2000 mg per day.
The compounds of formula (I), and pharmaceutically acceptable derivatives thereof, may be used on their own, or in the form of appropriate pharmaceutical compositions in which the compound of derivative is in admixture with a pharmaceutically acceptable adjuvant, diluent or carrier. Administration may be by, but is not limited to, enteral (including oral, sublingual or rectal), intranasal, intravenous, topical or other parenteral routes. Conventional procedures for the selection and preparation of suitable pharmaceutical formulations are described in, for example, xe2x80x9cPharmaceuticalsxe2x80x94The Science of Dosage Form Designsxe2x80x9d, M. E. Aulton, Churchill Livingstone, 1988. The pharmaceutical composition preferably comprises less than 80% and more preferably less than 50% of a compound of formula (I), or a pharmaceutically acceptable salt, enantiomer or racemate thereof.
There is also provided a process for the preparation of such a pharmaceutical composition which comprises mixing the ingredients.
The compounds of formula (I), and pharmaceutically acceptable derivatives thereof, may also be advantageously used in combination with a COX-2 inhibitor. Particularly preferred COX-2 inhibitors are Celecoxib and MK-966. The NOS inhibitor and the COX-2 inhibitor may either be formulated together within the same pharmaceutical composition for administration in a single dosage unit, or each component may be individually formulated such that separate dosages may be administered either simultaneously or sequentially.
The invention is illustrated, but in no way limited, by the following examples:


An optical ferrule comprising: (a) a body defining an end face; (b) one or more channels extending from said end face through said body, each channel adapted to receive an optical fiber; and (c) first and second alignment pin channels defined in said end face, each alignment pin channel having a center point, said center points being disposed along a first axis, said first alignment pin channel having a first cross section essentially the same as that of an alignment pin and being adapted to receive said alignment pin, said second alignment pin channel having a second cross section elongated along said first axis.

Optical fiber connectors are an essential part of substantially any optical fiber communication system. For instance, such connectors are used to join segments of fiber together, to connect fiber to active devices such as radiation sources, detectors and repeaters, and to connect fiber to passive devices, such as switches, multiplexers, and attenuators.
A typical optical fiber connector comprises housing and a ferrule assembly within the housing. The ferrule assembly comprises a ferrule, which has one or more fiber channels to accommodate fibers, and a fiber secured in each channel such that the end of the fiber is presented for optical coupling by the ferrule. The housing is designed to engage a "mating structure" having an optical path to which the fiber optically couples during mating. The mating structure may be another connector or an active or passive device as mentioned above. The optical path may be, for example, a fiber in a ferrule, a waveguide in a substrate, a lens, or an optically-transparent mass. The principal function of an optical fiber connector is to hold the fiber end such that the fiber's core is axially and laterally aligned with optical pathway of the mating structure. This way, light from the fiber is optically coupled to the optical pathway. If the cores of the mating fibers are not precisely aligned, the optical coupling suffers attenuation.
Of particular interest herein, are ferrules having alignment features such as the mechanically transferrable (MT) ferrule 200, shown in FIG. 2. The MT ferrule 200 is generally used for multi-fiber applications and thus has a row 201 of fiber channels 202, and is characterized by alignment pin channels 203 and 204 defined at each end of the front face of the ferrule. Alignment pins (not shown) are inserted in the alignment pin channels of mating ferrules such that the ferrules mate in a precise orientation, thus ensuring that the cores of fibers held in the mating ferrules are aligned.
To ensure proper alignment, the alignment pin channels are positioned to minimize angular misalignment. Specifically, referring to FIG. 2, the alignment pin channels 203, 204 have centers 203a, 204a, respectively, which are aligned along an axis 205. It is important that the axis be as close as possible to parallel with the row 201 of fiber channels 203. (In the ferrule 200 shown in FIG. 2, the row is coincident with the axis 205, although in multiple row MT ferrules this would not be the case.) Having the axis 205 parallel to the row 201 is an important parameter to ensure that the fiber cores of mating ferrules are aligned. By way of contrast, if the alignment pin channel 204′ were offset along the y axis as shown (greatly exaggerated), the axis 205′ joining the centers 203a and 204a forms an angle α with the row 201. This angle α is referred to herein as angular misalignment.
The tolerance for angular misalignment of MT ferrules has become more stringent as the use of the MT ferrule has evolved. The MT ferrule was initially introduced as a multi-mode ferrule. A multi-mode fiber has a relatively large core diameter of about 50 microns, and thus aligning the cores of mating ferrules it relatively simple compared to single mode applications. Additionally, because multi-mode applications were usually short-distance applications, relatively high loss, for instance, about 1 dB, could be tolerated. Consequently, the tolerances of a multi-mode ferrule were relatively relaxed, allowing an angular misalignment of about one degree.
As the MT ferrule evolved and was applied to single mode applications, the angular tolerance was reduced. Specifically, a single mode fiber has a relatively narrow core of about 9 microns. Accordingly, any misalignment of a single mode fiber results in significant attenuation. Additionally, given the long range applications in which single mode fibers applications are typically used, very little loss can be tolerated, for example, less than 0.2 dB. Therefore, for the MT ferrules to accommodate this low loss requirement, the angular misalignment tolerance of a single mode MT connector is about 0.5 degrees. This is significantly less than the multi-mode application. Furthermore, in certain "low loss" single mode applications this angular misalignment is further limited to just 0.2 degrees.
Despite the exacting angular misalignment tolerance and other tight tolerances of the single mode MT ferrules, Applicants have discovered several problems with their performance. In particular, performance repeatability of mated MT single mode ferrules varies considerably. For example, a particular optical coupling in mated single mode MT ferrules may be satisfactory in one instance, but when the ferrules are re-mated, its performance may drop considerably. Additionally, Applicants have discovered that the optical coupling performance between fibers varies considerably during thermal cycling of single mode MT ferrules. For example, referring to FIG. 5, the attenuation of a given optical coupling varies with temperature cycling between 60 and −10° C. Moreover, Applicants discovered an initial jump in attenuation during the initial temperature cycle. The optical coupling's performance never recovered from this initial jump, even after the temperature was lowered.
Therefore, what is needed is an MT ferrule suitable for single mode applications that provides consistent optical performance over repeated mating cycles and thermal cycles. The present invention provides this need among others.


A method for providing multi-tenant services includes receiving a request from a user, establishing tenancy information for the user, wherein the tenancy information is selected which corresponds to a tenant of the user from among multiple tenants, customizing the request according to the tenancy information established for the user, forwarding the request to an application that is not multi-tenant aware, receiving results of the request from the application, customizing the results according to the tenancy information established for the user and corresponding to the tenant of the user, and returning customized results to the user.

1. Technical Field
The present invention relates to software provided as a service, and more particularly to a system and method for processing requests from multiple tenants.
2. Discussion of Related Art
Software-as-a-Service (SaaS) lowers the cost of development, customization, deployment and operation of a software application while supporting multiple tenants over the Internet. In general, SaaS is associated with business software applications. SaaS is a Web-based software application deployed and operated as a hosted service over the Internet and accessed by users.
In a SaaS model, multi-tenancy support can be applied to four different software layers: the application, middleware, the Virtual Machine (VM), and the operating system layers. Referring to FIG. 1, for the application layer, there are four levels of SaaS maturity model. Level one 101 has a separate instance for each tenant's customized code base and it is similar to the Application Service Provider (ASP) software application model. Level two 102 has a separate instance for each tenant but the instances come from a single code base with configuration options. Level three 103 has a single instance for all tenants with configurable metadata for each tenant. Level four 104 has a load-balanced farm of identical instances with configurable metadata for its tenants.
Contract management is an example of a SaaS application of the level three type; Contracts are required in most business transactions as they constitute the binding relationships between parties. Automation of some contract management tasks in the electronic contract lifecycle creates a substantial value. This value stems from improved productivity and security, effectively aggregated contract information; accelerated contract transaction time and lifecycle processes; reduced contractual errors and risk; enabled revenue forecast and profit optimization as well as better compliance enforcement Different companies have different requirements on presentations, business rules, workflows, document flows, database and security in managing their contracts.
In most commercial electronic contract management applications available today, different customized code base has to be developed, deployed and operated to support each tenant. Few advanced commercial electronic contract management applications use a single code base with configuration options to support multi-tenants. However, typically a separate instance of the code base still needs to be deployed and operated for each tenant even in these applications to achieve scalability. Development and maintenance costs associated with a service or business model supporting a single application instance for each tenant, e.g., as in an electronic contract management application and other business applications, can render such a service unaffordable for some tenants.
Therefore, a need exists for a system and method for a non-tenant aware SaaS application supporting multi-tenancy.

System and methods to create a multi-tenancy software as a service application

International Business Machines Corporation


A method for transferring a data packet from a compressor to a decompressor said data packet including a header with header data fields. A number of the header data fields that remain constant during the data transfer are stored in the decompressor. In a compressed data packet, a header data field that varies is replaced by a compressed value identifying a data packet in a compression sequence. In the decompressor context data comprising information for relating the received compressed value to a corresponding compression sequence is maintained and the information is updated according to the received compressed values. The compressed value and the information of the corresponding compression sequence are used for mapping the compressed value into a decompressed header data field. Thus compressed data is unambiguously mapped to a full packet data header field in the decompressor side throughout the session.

The present invention relates to data transmission and especially to a method for transferring a data packet from a compressor to a decompressor, said data packet including a header with header data fields, a number of the header data fields that remain constant during the data transfer being stored in the decompressor. The method comprises sending from the compressor and receiving at the decompressor a data packet comprising information on one or more header data fields that vary during the data transfer; and decompressing the header using the stored header data fields and the received information on the one or more header data fields that vary during the data transfer. The invention also relates to access network elements implementing the invented method.
Real time services constitute an emerging set of technologies that enable voice, data and video collaboration over packet switched networks. Along the standardisation of packet switched radio systems interest in providing real time services also through wireless networks has risen. In real time services packet transmission is carried out using a number of protocols. This introduces a large protocol overhead and causes inefficient bandwidth usage. As the transmission rates in wireless systems are limited, transferring of large headers mean wasteful use of capacity.
To overcome the problem of large headers, a variety of header compression schemes have been introduced. Publication xe2x80x9cCompressing IP/UDP/RTP Headers for Low-Speed Serial Linksxe2x80x9d by S. Casner and V. Jacobson, Intemet Engineering Task Force, INTERNET-DRAFT, draft-ietf-avt-crtp-05.txt, July 1998 presents effective header compression algorithms that enable header size reduction by a magnitude. The presented header compression is based on the fact that some of the bytes in the IP, UDP and RTP headers remain constant over the life of the connection. After sending an uncompressed header these fields may be elided from the compressed headers that follow. Furthermore, differential coding is used on the changing fields to reduce their size. In RTP header the difference from packet to packet is often constant and therefore also the second order difference is zero. By maintaining both the uncompressed header and the first order differences in the session state shared between the compressor and decompressor, it is mainly necessary to indicate that the second order difference between successive packets is zero. It is also suggested that a compressor implementation might maintain state for multiple session contexts. Using a hash function on certain predefined fields to index a table of stored session contexts, and including a session context identifier in compressed packets would enable the decompressor to index a table of stored session contexts directly.
Real time services cause strict limits for transmission delays and therefore normal retransmission procedures (e.g. in Transport Control Protocol, TCP generally used for transmission of IP packets) are generally not applicable. Thus, a link in real time services in practice will be considered a simplex link. In the prior art reference, for simplex links a periodic refresh scheme is suggested. Whenever the decompressor detects an error in a packet stream, it discards all packets in that stream, and will not resume decompression until a regularly transmitted uncompressed header (refresh header) is received. This means that after a transmission error all packets until the next refresh packet are lost. In transmission links where errors occur relatively seldom this does not have much effect on the transmission throughput. Anyhow, when a link with high risk of multiple transmission errors is involved, the effect is disruptive. This is especially the case with wireless transmissions.
A publication xe2x80x9cLow-loss TCP/IP header compression for wireless networksxe2x80x9dn by Mikael Degermark, Mathias Engan, Bjxc3x6rn Nordgren and Stephen Pink, Wireless Networks 3 (1997) 375-387, J. C. Balzer A G, Science Publishers presents header compression schemes for UDP/IP and TCP/IP protocol where the problem of simplex links and lossy links have been dealt with. In the presented system the compressor sends a full header and a compression identifier, which is a small unique number also carried by compressed headers. The full header is stored as a compression state by the decompressor. The compression identifiers in compressed headers are used to lookup the appropriate compression state to use for decompression. To avoid incorrect decompression due to inconsistent compression state some further mechanisms are introduced. Each version of the compression state is associated with a generation, represented by a number, carried by full headers that install or refresh that compression state and in headers that were compressed using it. Thus the decompressor is able to detect when its compression state is out of date by comparing its generation to the generation in compressed headers. Furthermore, to avoid long periods of packet discard when full headers are lost and on the other hand to get as high compression rates as possible, the compressor starts with a short interval between full headers, and the refresh interval is exponentially increased with each refresh until a steady state refresh period is reached (compression slow-start). A modest trade-off of some header compression is also suggested.
Though the use of compression state generation facilitates easier detection of inconsistent compression states, the packets will anyhow be lost until a full header installs a proper compression state. Compression slow-start helps finding a convenient trade-off between the compression rate and acceptable recovery time, but in difficult transmission conditions, the compression rate will anyhow be compromised and the advantage of header compression will be diminish.
Now a method and network elements implementing the method have been invented, with the help of which these problems can be avoided or their effect can be reduced.
According to a first aspect of the present invention there is provided a method for transferring a data packet from a compressor to a decompressor said data packet including a header with header data fields, a number of the header data fields that remain constant during the data transfer being stored in the decompressor. The method comprises sending from the compressor and receiving at the decompressor a data packet comprising information on one or more header data fields that vary during the data transfer; decompressing the header using the stored header data fields and the received information on the one or more header data fields that vary during the data transfer. The method is characterised by sending from the compressor and receiving at the decompressor a compressed value for a header data field, said compressed value identifying the data packet in a compression sequence; maintaining in the decompressor context data comprising information for relating the received compressed value to a corresponding compression sequence, the information being updated according to the received compressed values; and using the compressed value and the information of the corresponding compression sequence for mapping the compressed value into a decompressed header data field.
The advantage of the invention is based on the fact that most of the fields in the network layer packet remain constant throughout a session. Network layer in this context refers to packet data network level protocol layers, referring to e.g. IP, UDP and RTP protocols. Furthermore, it is appreciated that changes in the fields that vary from packet to packet are predictable. Such fields are sent in a compressed form to the decompressor. Based on the prior knowledge of the anticipated changes, the decompressor will generate and maintain context data that is updated with the information from the packets that are received in the decompressor. Compressed data maps unambiguously to a change in a decompressed value in a set of consecutive data packets, a compression sequence. In the context data, information on one or more compression sequences is maintained. This information provides means for associating the received compressed data with a correct compression sequence. Using the received compressed data with the corresponding context data maintained in the decompressor enables the compressed data to be unambiguously mapped to a full packet data header field in the decompressor side throughout the session. Preferably, data packets carrying information that can not be correctly associated with any of the compression sequences of the context data maintained in the decompressor are filtered out already in the compressor side. Compared to the earlier solutions, the compression in the invented method is increased since also the varying fields that are related to identification of packets can be compressed. Still, transmission errors will have effect only on transmission of individual packets and problems in transmission of one packet do not escalate to subsequent packets. The scheme of refreshing complete header information can be designed to occur at longer intervals, or it can be abandoned altogether. Further aspects of the invention are presented in the independent claims 9, 13 and 15. Preferred embodiments are presented in the dependent claims.


The invention relates to construction principles, operating and manufacturing methods for inertial sensors, i.e., sensors for rapidly detecting movement and acceleration in all degrees of freedom in space, and for separately detecting the position with respect to the perpendicular under the action of acceleration due to gravity.

Thermodynamic sensors for detecting inclination and acceleration are known from DE 42 43 978 C1. Temperature-dependent electrical resistances of which at least one is heated are arranged in a closed fluid-filled capsule. The convective flow established in a gravitational or inertial field is evaluated.
EP 1 111 395 A1 and U.S. Pat. No. 6,722,199 B2 describe sensors for detecting rate of rotation, rotational acceleration and inclination based on the principle from DE 4243978 C1. Also known are other thermodynamic sensors wherein the temperature differences in the convective flow field are detected, for example, by thermoelements (thermopiles).
In these known sensors it is initially assumed that the measuring elements must adapt to the respective temperature of the isotherms in the convection field during an inclination or acceleration. Even if the mass of the measuring elements is small, this thermal adaptation takes a certain time. Thus, the response time of the sensors is frequently too high and the limiting frequency relatively low. In known sensors the signals for the inclination and acceleration cannot be directly discriminated.
Sensors based on density differences in fluids and methods for operating and for manufacturing said sensors are known from DE 103 48 245.8-52 of the applicant. Unlike previously described operating methods using sensor elements which adjust to a new temperature in a stationary isothermal field during a movement or change in position, in this case cyclic density fluctuations are generated by a transmitting element, received by a receiver and substantially time shifts (e.g., of the temperature variations) which are seen during movement or change in position are detected.
In claim 6 of the patent specification DE 42 43 978 C1 reference is already made to the possibility of regulating at least one of the temperature-dependent elements at constant temperature. No specific instruction as to how this operating variant can be advantageously used is found either in this patent specification nor in other relevant documents.
It is the object of this invention to describe the structure, operating mode and method of manufacture of fluid-filled thermodynamic sensors for detecting movement, acceleration and measured quantities attributable to acceleration where lateral and vertical acceleration, rate of rotation and rotational acceleration can be assigned and, under the action of acceleration due to gravity, a separate identification of position with respect to the perpendicular can be made. It is further the object of the invention to provide conditions for fast response, high limiting frequency, self-testing capability, independent after-calibration, monitoring of fluid density, best possible accuracy and long-term stability of said sensors.
The proposed sensors should be suitable for individual quantities or for a selection of or for all said quantities (inertial sensor) and preferably should be manufacturable using Microsystems technology.
When designing the sensors, broadly all acting forces and effects (inertia, Earth's attraction, centrifugal acceleration, Coriolis effect etc.) should be taken into account.
The operating modes should be described including specific circuits.

Sensors for detecting position, inclination to perpendicular, movement and acceleration based on thermodynamic effects and method for operating and for manufacturing said sensors

Abstract: Use is made of the knowledge that to maintain a common convection zone of two or more sensor elements, the power fractions supplied to these elements vary with change in position, movement and acceleration.


An earthworm collecting device that is highly effective in causing earthworms to surface from their holes during the day time or at night and come to the surface. The device generates a rasping noise and a series of vibrations that resonate through the ground. These resonating vibrations cause the earthworms to surface which then allows for easy and rapid collection.

1. Field of the Invention
This application relates generally to the procurement of earthworms for fishing bait, and has particular reference to an improved mechanical means that causes worms to leave their holes and come to the surface of the ground where they can easily be collected for use.
2. Description of the Prior Art
Devices for inducing earthworms to come out of the ground so that they can be collected for bait have been described. For example, compositions have been described which contain a substance that acts as a minor irritant to the worms, making them want to get above ground. Normally, the prepared composition is mixed with water and spread on the ground. As the soil absorbs the mixture, the worms begin to surface. An exemplary composition has been described in U.S. Pat. No. 4,556,679. Adding a chemical to the soil is not environmentally sound and may even damage the worms themselves.
Kiss (U.S. Pat. No. 4,147,256) describes a vibrational separator for harvesting worms living within a bedding apparatus using a frame and screen device which vibrates to separate the worms from their bedding material. Another harvester as described by Stevenson (U.S. Pat. No. 4,187,946) harvests worms from a trough-like bed with a digger that separates worms by raking the bedding pulling the worms toward a conveyor belt. However, both devices are expensive, not easily transported, and can't capture worms in their natural habitat or soil.
An electric worm collecting apparatus has also been described for capturing worms at the surface from soil electrically shocked (Schommer U.S. Pat. No. 3,973,354). The device consists of an electrical conducting rod having an end portion which is inserted into the ground. The rod generates an AC voltage that is channeled into the ground and surrounding soil, causing damage to the worms which may migrate to the surface.
A device is needed to collect earthworms from their natural environment using a simple and easy method that does not require preparation of caustic chemicals or the use of an elaborate apparatus, and yet is safe for the environment. The present invention embodies such a device and method using a portable vibrational device that sends sound waves through the ground to disturb the earthworms and force them to the surface for collection.

Method and device for attracting and collecting earthworms


A head cover that can be worn by health care professionals is provided. The head cover includes an anterior portion with a height h, a posterior portion with a height h2, at least one side portion or panel which may be shaped and sized so as to connect the anterior portion of the head cover and the posterior portion of the head cover, and where the at least one side portion has a contoured section t that forms all or a portion of a bottom edge of the side portion and that is shaped and sized so as to cover the ears, scalp, and sideburns of a user as required by AORN guidelines while also remaining clear of a user's eyes and field of vision.

Health care professionals often wear a surgeon's cap, a bouffant cap (i.e., hair net), or both during medical procedures to prevent contact with hazardous materials including blood or other bodily fluids. In addition, health care professionals are often required to wear a surgeon's cap or a bouffant cap (i.e., hair net) to cover their hair to protect the sterile environment. Moreover, the Association of Registered Nurses (AORN) Guidelines are undergoing revisions, and it is now recommended that head coverings should cover the head, hair, ears, facial hair, and nape of the neck to not only protect health care professionals but to maintain a sterile environment as well. However, traditional surgeon's caps do not cover the ears or the nape of the neck, requiring health care professionals to also don a bouffant cap or hair net to try to cover these regions. Bouffant caps add an additional layer of PPE which can trap heat and increase bulk. Further, bouffant caps are prone to leave red marks and indentations on the forehead after use due to the use of an elastic band to secure the bouffant caps around the head.
One solution is to don a bouffant cap only instead of a bouffant cap and surgeon's cap. However, bouffant caps generally cannot support the use of headlamps or other equipment that may be used by a health care professional. Hence, it is necessary to don both a bouffant cap and a surgeon's cap, as the surgeon's cap has sufficient bulk and structure to support headlamps and other equipment. Nevertheless, problems also exist with the use of a surgeon's cap. Namely, typical surgeon's caps only come in a few sizes and do not provide a secure enough fit for many health care professionals. In addition, although surgeon's caps may be outfitted with ties, the repetition of tying a surgeon's cap to secure its fit over an extended time period can lead to shoulder pain and other issues.
Further, many head covers used during procedures are constructed of non-wettable materials. Particularly, materials such as spunbond or meltspun polyolefin materials lack breathability and wettability, and may result in sweating in various areas of the head due to stress, temperature, and/or personal predisposition to perspiration. Thus, such head covers may cause unsanitary and uncomfortable situations as the material allows sweat to drip into the eyes and onto sterile surfaces.
Consequently, there is a need for a head cover that overcomes the aforementioned shortcomings of existing surgeon's caps and bouffant caps. In particular, a head cover that covers a health care professional's hair without the need to wear a surgeon's cap and a full bouffant cap would also be useful. Additionally, it would be beneficial to provide a head cover that fits a large portion of potential users without the need for adjustment. Furthermore, it may be beneficial to provide a head cover that has improved breathability and/or wettability.

Full coverage head cover made with wettable material


A cervical plate assembly is disclosed. The cervical plate assembly includes a base plate including: (1) at least two bone screw seats, each bone screw seat including a borehole dimensioned to receive a bone screw, and (2) a first blocking seat positioned between the at least two bone screw seats. The cervical plate assembly includes a blocking mechanism retained within the first blocking seat of the base plate. The blocking mechanism is selectively positionable between a closed position in which the blocking mechanism obstructs at least one bone screw seat to retain a bone screw with the base plate, and an open position in which the bone screw seats are unobstructed.

Certain surgical procedures require a surgeon to fuse portions of a patient's spine to each other. Implanting a cervical plate reduces a patient's range of motion, and helps relieve pain experienced by a patient. Although cervical plate implantations are used to treat radiculopathy or myelopathy, but one of ordinary skill in the art would recognize that fusion can be used for other types of surgery.
Anterior cervical plate assemblies typically include a base plate defining through openings for bone screws to anchor the base plate to a patient's spine. Some cervical plate assemblies include a blocking mechanism to prevent the bone screws from inadvertently backing out of the base plate. One type of known blocking mechanism includes an automated blocking feature, such that once a bone screw passes a predetermined threshold then the blocking mechanism is automatically activated to block the bone screws from inadvertently backing out of the plate. These automated blocking mechanisms can be complicated for surgeons to operate, and can make removal of the base plate difficult.
Other known blocking mechanisms for anterior cervical plate assemblies rely on a patient's bones to have a certain strength characteristic to withstand the blocking mechanism features. Some known types of blocking mechanisms require force for removing a screw from the blocking mechanism. However, this type of blocking mechanism can cause stripping of the screw holes for bone screws implanted in a patient's bones.
Another known type of blocking mechanism for anterior cervical plate assemblies requires additional steps to install and lock the blocking mechanism screw in the plate. In some devices, this additional step requires a specialty tool or instrument. These steps are time consuming and require the surgeon to perform additional steps during surgery, which is undesirable.
It would be desirable to provide an improved cervical plate assembly that is relatively simple to use and provides a reliable blocking function.


A diamond-shaped actuator for a flexible panel has an inter-digitated electrode (IDE) and a piezoelectric wafer portion positioned therebetween. The IDE and/or the wafer portion are diamond-shaped. Point sensors are positioned with respect to the actuator and measure vibration. The actuator generates and transmits a cancelling force to the panel in response to an output signal from a controller, which is calculated using a signal describing the vibration. A method for controlling vibration in a flexible panel includes connecting a diamond-shaped actuator to the flexible panel, and then connecting a point sensor to each actuator. Vibration is measured via the point sensor. The controller calculates a proportional output voltage signal from the measured vibration, and transmits the output signal to the actuator to substantially cancel the vibration in proximity to each actuator.

The structural vibration of a flexible panel or another flexible component can generate undesirable noise, particularly within an enclosure constructed using such panels. For instance, aluminum panels of an aircraft fuselage can vibrate when the aircraft is in flight, which in turn can generate substantial noise within the aircraft. Mitigation of such acoustical/structural resonance may include the use of passive or active damping techniques. As an example, a compliant damping mechanism may be used to dissipate vibration energy as heat. Other approaches may include the use of sound absorbing materials. Active damping techniques, by way of contrast, involve the active, targeted use of force actuators to produce an actuation force that at least partially counteracts a resonant vibration within a particular range of frequencies. However, conventional approaches to active damping may be less than optimal when used with flexible panels.

Compact active vibration control system for a flexible panel

The United States of America as represented by the Administrator of the National Aeronautics and Space Administration


An oral irrigator has a removable reservoir defining a reservoir cavity, a base unit housing a motor and a pump, and a handle for directing fluid flow from the pump removably connected to the base unit and fluidly coupled to the pump by a hose. The handle has a housing defining a slot formed in an outer wall of the housing. The slot is bounded by two opposing walls spaced apart from each other and a transverse wall at a terminal interior end of the opposing walls. The outer wall of the housing is open to the slot at lateral sides of the two opposing walls and at a base end of the opposing walls opposite the transverse wall.

Oral irrigators typically are used to clean a user's teeth and gums by discharging a pressurized fluid stream into a user's oral cavity. The fluid impacts the teeth and gums to remove debris. Countertop oral irrigator units include a large reservoir that connects to a base unit housing the pump and other internal components. These units are typically too large to be easily portable and therefore many users do not travel with countertop units. Handheld oral irrigator units are smaller than most countertop units and may include a handle housing internal components, such as a pump, motor, etc., and a reservoir integrated with the handle or connected to the handle. While handheld irrigator units are typically smaller than countertop units and more easily portable, because the reservoir is connected to the handle, it often is smaller than countertop unit reservoirs and thus may not provide as much fluid for irrigating as desired by a user.
The information included in this Background section of the specification, including any references cited herein and any description or discussion thereof, is included for technical reference purposes only and is not to be regarded subject matter by which the scope of the invention as defined in the claims is to be bound.


The pump for generating pressure or negative pressure comprises a pump chamber (32) which has a high-pressure port and a low-pressure port. Two rotors (28, 30) having at least two blades are fitted to two parallel shafts (20, 22) in the pump chamber (32) that are offset to each other, the shafts defining an axial direction. A drive (10) is arranged on an end face of the rotors (28, 30) and a housing cover (34) is arranged on the opposite side. The housing cover (34) is configured cup-shaped and the high-pressure port (42) as well as the low-pressure port (40) are integrated in the housing cover (34). The inner wall (44) of the housing cover (34) delimits the pump chamber (32) on an end face and has two axial openings (46, 48) one each adjoining by one channel (40, 42) which is integrated in the body of the housing cover (34). The axial opening (48) for the high-pressure port, in operation of the pump, is covered by one of the rotors (28, 30) for a time to enable inner compression of the delivered medium.

The invention relates to a pump for generating pressure or negative pressure, and, more particularly to a pump comprising a pump chamber which has a high-pressure port and a low-pressure port, two rotors having at least two blades and fitted to two parallel shafts in the pump chamber that are offset to each other, a drive arranged on an end face of the rotors, and a housing cover arranged on the opposite side.
With pumps of this type, the blades of the rotors engage each other without having any contact, so that a lubricate-free operation is made possible. Hence, there are manifold fields of application for such pumps. Due to the manifold application possibilities of these pumps, an optimization with respect to the size, the weight and the production costs is aimed at.
From U.S. Pat. No. 4,057,375 there is known a positive-displacement pump comprising two blade wheels which rotate in synchronism and with opposite sense of rotation, and the blades of which, due to their meshing engagement, form distinct spaces with changeable volume during the rotary motion; in these spaces, a compressed flow medium is conveyed from the low-pressure side to the high-pressure side, the flow medium being conveyed in a direction perpendicular to the two axes.
Further, in GB 2 139 287 A there is disclosed a hydraulic pump comprising two toothed wheels being in meshing engagement, which are disposed in a chamber into the envelope of which open inlet and outlet channels.
With these known pumps, the rotors are supported on both sides, i.e. on each of the two axle ends. The pump chamber is limited on both end faces by a part of the housing cover. The suction and pressure channels open into the envelope of the pump chamber.
In EP 0 389 838 A2 there is described a rotating piston pump in the form of a roots compressor having two rotors which are arranged cantilevered on two axles being parallel to each other and which make possible the continuous conveying of various incompressible flow media. The rotors are disposed in a chamber which on the side of the gear box is limited by a flat platexe2x80x94through which the axles of the rotors are passed in a fluid-tight mannerxe2x80x94and on the side facing away from the gear box is limited by a housing cover in the envelope of which are arrangedxe2x80x94guided radially to the outsidexe2x80x94connection ports for inlet and outlet.
The invention provides a pump enabling inner compression of the medium to be delivered, the pump having a space-saving and simple structure and allowing to provide the low-pressure and high-pressure openings on the housing in an end face position.
This is achieved according to the invention in that the housing cover is configured cup-shaped and the high-pressure port as well as the low-pressure port are integrated in the housing cover, the inner wall of the housing cover delimiting the pump chamber on an end face and having two axial openings for the high-pressure and the low-pressure port and the axial openings each being adjoined by one channel which is integrated in the body of the housing cover, the axial opening for the high-pressure port, in operation of the pump, being covered by one of the rotors for a time to enable inner compression of the delivered medium.
Preferably, the axial opening for the high-pressure port is significantly smaller than the axial opening for the low-pressure port. Thus, the opening for the high-pressure port can be easily covered by for a time by one of the rotors with its claw-shaped blades, in contrast to the relatively large opening for the low-pressure port through which medium is continuously delivered into the pump chamber.

Rotary pump having high and low pressure ports in the housing cover


The dispenser (1) includes a body (2) made of two separable parts (2a; 2b). The front part (2a) receives a reservoir (4), containing the product (3) to be dispensed, between an outlet opening (5) and a piston (6), which is controlled by a rod (7) that is displaceable translationally and incrementally by a mechanism (8) housed in the rear part (2b). The rod (7) includes rear catches (29a) and front catches (29b) that normally mesh with the notches (22), and elastic regions (28) between the catches that exert a restoring force on a pushbutton (9) closing the rear part (2b). Rotation of the pushbutton (9) by 90 degrees drives the cage in rotation and puts it in a position in which the catches bear on the flats (21), which disengages the mechanism. In the engaged position, any thrust on the pushbutton brings about an advancement of the rod (7) equal to one notch in a rack.

Dispensers of the type described above are already on the market. In these dispensers, the piston that pushes the product to be dispensed in the direction of the dispensing opening is mounted on the end of a threaded rod, which cooperates with a fixed nut integrally joined to the reservoir containing the product. The threaded rod is displaceable in rotation by means of a mechanism that converts the action of the user on a pushbutton of the dispenser into a rotation of slight angular amplitude; the rotation of the threaded rod, which cooperates with the aforementioned fixed nut, is converted into translation of the rod with respect to the reservoir, the amplitude of the translation being increasingly small, the smaller the rotation of the rod, on the one hand, and the smaller the pitch of the thread of the rod, on the other. For each action upon the pushbutton of the dispenser, a translation of several tenths of a millimeter is obtained, which is entirely satisfactory for dispensing the product. A dispenser of this type that can be used for a liquid product is described in particular in French Patent 2 555 471.
However, the mechanism disposed between the pushbutton and the piston is very expensive, partly because of the number of parts comprising it and partly because of the complexity of molding of the parts, as well as the difficulty of assembling the mechanism. The function of such a mechanism is irreversible; when the piston arrives in the vicinity of the reservoir dispensing opening, it cannot be made to move backward in order to refill the reservoir; the only way to reverse it would be to screw the threaded rod backward in its nut, but it is understandable that the user would not think of that. As a result, the mechanism of such a dispenser must be considered a throwaway item, and its cost considerably increases the cost price of the dispenser filled with the product to be dispensed.
To overcome these disadvantages, it has been proposed, in French Patent Application 88-05026 filed on April 15, 1988, that the support of the mechanism enabling the incremental rotational displacement of the threaded rod, which is likewise the support or the nut, includes a means of integral attachment to the reservoir, making the reservoir detachable with respect to this support; that the nut, which cooperates with the threaded rod, is slit along at least one diametral plane over the entire height of its threaded bore, with the sectors of the nut then being kept together by a flexible zone that assures the fixation of the nut on the support; and that the reservoir includes a frustoconical bearing that when the detachable reservoir is attached to the support presses against a corresponding frustoconical bearing of the nut and/or support, in order to assure the squeezing of the sectors of the nut around the threaded rod driven by the mechanism. With such a structure, the intended object can be attained, that is, to re-use the same mechanism for dispensing the product from several reservoirs in succession. Nevertheless, the mechanism itself remains the same as the type described in French Patent 2 555 471, that is, a mechanism, that is intrinsically very expensive, for the reasons already given above.

Dispenser including a translatable piston


A portable input device includes a casing, a light sensing module and a printed circuit board. The casing includes a reflecting member. The light sensing module is movably mounted on the reflecting member and exposed from the casing. The light sensing module includes a lighting member and a sensor both facing the reflecting member. The lighting member is adapted for emitting light to the reflecting member. The sensor is adapted for receiving the light reflected by the reflecting member and configured for transmitting a sensing signal. The printed circuit board is mounted on the casing and electrically connected to the light sensing module. The printed circuit board is configured for processing the sensing signal to compute a value of movement of the light sensing module moving with respect to the reflecting member.

So far, users may employ multiple different input devices to command or control an electronic device which execute or process data or information needed by the user. For instance, a remote control, which is taken as the input device, is used by the user to emit infrared to an electronic device (e.g., a television) such that the electronic device executes a certain specific program for the user accordingly.
With the development of technology, the boundary between television and computer is blurred. That is, users may not only watch television programs or films but also control multimedia programs on an operating system of the television. For instance, the operating system has a graphic interface, the user may control a cursor on the graphic interface to move to a position the user desired. Then, the user presses a button of the remote control to send a command to the operating system of the television. Specifically, the remote control comprises several buttons for controlling the movement of the cursor in a digital manner. Alternatively, the remote control may comprise a joystick to control the movement of the cursor in an analogical manner.


A method and terminal for controlling Voice Call Continuity (VCC) functions initiated by a network, are discussed. According to an embodiment, the method includes receiving, by a terminal, a VCC function notification message, the VCC function notification message including VCC enabling information indicating whether a VCC function of the terminal is to be enabled or disabled; and enabling or disabling the VCC function of the terminal based on the VCC function notification message.

1. Field of the Invention
The present invention relates to a Voice Call Continuity (VCC), and more particularly, to a method and system for controlling VCC functions initiated by a network in which the VCC functions are enabled or disabled by exchanging information regarding the VCC functions between a terminal and a network server. The present invention also relates to the terminal and network server for implementing the method.
2. Discussion of the Background Art
In general, a Voice Call Continuity (VCC) refers to a service for allowing a call path exchange of voice calls between a 3GPP Circuit Switching (CS) system (e.g., GSM, UMTS) and an IP Multimedia Subsystem (IMS). That is, the VCC refers to a type of application, namely, a home IMS application which is capable of transporting voice calls between the CS domain and IMS domain. As such, the VCC provides functions of voice call originations, voice call terminations, a domain selection and a domain transfer from the CS domain to the IMS domain or vice versa. Here, the domain transfer refers to transferring access legs for voice calls toward a User Equipment (UE) (i.e., a terminal) from the CS domain to the IMS domain or vice versa during an active session. The access leg denotes a call control leg between a VCC UE and a Domain Transfer Function (DTF) of a VCC application (server).
Through the domain transfer procedures of the VCC service, continuity for one or more voice sessions is provided between the IMS domain and CS domain while the VCC UE performs the one or more voice sessions. That is, the VCC services provides continuity to the voice call by switching from the IMS domain to the CS domain or vice versa, e.g., when the current domain for the call is not suitable or desired.
The domain transfer for a certain voice call/session from the CS domain to the IMS domain or vice versa is initiated only when a DTF is positioned (located) on a signal path of the voice call/session setup. For this, positioning of the DTF on the way of the signal path of the voice call/session setup is referred to as anchoring in IMS or anchoring.
FIG. 1 illustrates an architecture of a network for providing a VCC service.
As illustrated in FIG. 1, a VCC UE 10 denotes all types of terminals which can support the VCC service. The VCC UE can access the CS and PS (packet switched) domains. That is, when accessing the CS domain, the VCC UE uses a UE-CS (not shown) provided therein, whereas the VCC UE uses a UE-IMS (not shown) provided therein when accessing the PS domain.
A VCC application 30 is an application server for providing the VCC service, and is constituted with entities which perform a series of functions. The series of functions may include functions required to setup voice calls toward the VCC UE, and functions required to switch an access leg of the VCC UE between the CS domain and the IMS domain with maintaining (performing) an active session. Here, the series of functions can be, but are not limited to, a Domain Transfer Function 30a, a Domain Selection Function 30d, a CS Adaptation Function 30b, and a CAMEL Service Application 30c. Detailed capabilities and operations for the series of functions are described in 3GPP TS 23.206 V1.2.0.
Generally, the CS domain entities include a Visited Mobile Switching Center (VMSC) 24, a Gateway MSC (GMSC) 26, a gsmSCF, and the like. The IMS domain entities include a P-CSCF (Proxy Call Session Control Function), a S-CSCF(Serving Call Session Control Function) 20, a I-CSCF (Interrogating Call Session Control Function), a Media Gateway Control Function (MGCF) and a Home Subscriber Server (HSS) 40.
In order for the VCC UE to receive the VCC services, a registration procedure to the CS and IMS domains must previously be performed. In the related art VCC technology the CS registration and IMS registration which are associated with the VCC are as follows.
Specifically, a registration (or an attachment) to the CS domain is performed as the same as an existing registration to the CS domain. The registration to the IMS domain can be performed by the VCC UE only when an IP connectivity is available. The successive registration procedures are performed depending on a subscriber's iFC (initial Filter Criteria). The iFC refers to filter criteria which are a type of user information stored in the HSS. For a VCC subscriber, registration in a third party registration is defined to be performed to the VCC Application Server (VCC AS) 30 depending on the iFC.
FIG. 2 is a signal flowchart illustrating a procedure in which a VCC UE registers in an IMS domain according to the related art.
As illustrated in FIG. 2, a VCC UE 10 sends a REGISTER message to a S-CSCF 20 to initiate (start) a registration procedure (S1).
The S-CSCF 20 sends information related to a user of the VCC UE 10 to a HSS 40, thereby requesting subscriber information (represented as 'Cx-Put/Cx-Pull' in FIG. 2) (S2). The S-CSCF 20 receives the subscriber information from the HSS 40 (represented as 'Cx-Put/Cx-Pull Resp' in FIG. 2) (S3). The S-CSCF 20 then performs a service logic based upon the received subscriber information (e.g., using the iFC included in the subscriber information) to determine if the registration should be allowed (S4), and then selectively performs a third party registration procedure with the VCC AS 30 based on the determination result (S5). The VCC AS 30 delivers a 200 OK message to the VCC UE 10 via the S-CSCF 20 after the third party registration procedure is successfully performed (S6 and S7).
Once the VCC UE 10 completes the registration for the VCC service through steps S1 to S7, the network may adapt the following logic for calls associated with the VCC subscriber (i.e., the user of the VCC UE 10).
Call origination: when the corresponding VCC subscriber originates a call (i.e., when the call is an outgoing call), an anchoring in the IMS domain is performed for the VCC.
Call termination: when the network receives a call which the corresponding VCC subscriber terminates (i.e., when the call is an incoming call directed to the terminal), an anchoring in the IMS domain is performed for the VCC. A CS domain or IMS domain is selected (i.e., a domain selection is performed) and the call is terminated in the selected domain.
Domain selection: the corresponding VCC subscriber (i.e., the VCC UE user) selects the currently activated domain or the most suitable domain based upon operator policy.
Domain transfer: domain transfer for an ongoing call is initiated from a first domain to a second domain, e.g., from the CS domain to the IMS domain or vice versa.
As such, the VCC functions can be performed after the VCC UE 10 registers in the network (i.e., VCC AS 30). However, some times the VCC functions can not be supported or performed by the network due to particular conditions of the network, for example, network maintenance, traffic, a load of a specific external node, an internal problem of the VCC AS 30, or a temporary (or permanent) change of operator policies. In such cases, however, since there is no way or mechanism for the VCC UE 10 to know the fact that the VCC functions cannot be supported by the network according to the background art, the VCC UE 10 ends up performing or initiating unnecessarily or uselessly VCC related operations (e.g., domain selection for outgoing calls, or domain transfer therefor). This, from the perspective of the VCC UE 10, degrades the efficiency or capabilities of the VCC UE 10, e.g., it can result in a waste of resources, CPU power loss, battery consumption, radio access monitoring, or the like.

Method for controlling VCC functions initiated by network and terminal and network server thereof


An optical integrator, comprising a solid integrator rod for internally reflecting light from an illumination source and transmitting the reflected light through an exit face thereof as a rectangular beam according to a predetermined aspect ratio, and a rectangular precision metal aperture with mirrored wall surfaces for extending the focal plane of the solid integrator rod beyond the exit face.

Optical integrator rods are well known components used primarily in illumination systems for electronic projectors. An optical integrator rod is a hollow, or solid internally reflective "light pipe" which uses multiple reflections of a focused light source to obtain homogenization of round or irregular patterns of illumination and convert them into a uniform rectangular pattern. This pattern can be imaged onto a panel such as an LCD (Liquid Crystal Display) or DMD (Digital Micromirror Device) by a relay lens system and then projected to a screen. Thus, the optical integrator rod is used to improve uniformity and efficiently match the aspect ratio of the illumination source to the panel.
There are two basic types of reflective integrators: a "tunnel" type made of four mirrors, and a solid glass integrator or "solid rod integrator". This latter type is more efficient than the former since it works on lossless multiple reflections using TIR (the Total Internal Reflection) of the glass rod.
As a practical measure adopted to improve handling and reduce chips in the glass, opticians normally require a chamfer on the sharp edges of the glass rod. This chamfer (or the micro chips that result if the chamfer is absent) are imaged onto the panel and may show up as defects on the edges of the final image. To prevent this, the state of the art is to either over fill the panel or provide a thin output aperture plate over the end of the rod that is smaller than the glass. This precision plate guarantees dimensional accuracy, and sharp comers, but because it masks the defects and chamfers, it is necessarily smaller than the output face, and therefore restricts some of the illumination. This figure often amounts to about 10% of the useable light.
In order to improve efficiency and brightness, prior art optical integrator rods require an output face that presents a clear, sharp and unobstructed illumination to be imaged onto the panel by the relay lens. Because the focus of the relay lens must be sharp at the aperture for efficiency, it is also often sharp enough to pick up dust and defects at the focal point (e.g. glass defects and particles on the glass output face). A common solution to this problem is to move the aperture plate out a small distance, in order to ensure that the depth of focus of the lens does not focus the dust or defects onto the panel and the projection screen. However, this solution further exacerbates the problem of decreased efficiency and light output resulting from use of a precision aperture.


A new and distinct Dracaena cultivar named ‘Dragonrayo’ is disclosed, characterized by dark green leaves, with a high gloss apperance. Plants grow rapidly. The new variety is a Dracaena, typically produced as an ornamental plant.

The new cultivar is the product of chance discovery. The new variety originated as a naturally occurring whole plant mutation of an unpatented, unnamed variety of Dracaena reflexa.
The new variety was discovered by the inventor, Ruud A. M. Scheffers, a citizen of the Netherlands, in 2006 in a commercial greenhouse belonging to the inventor in Honselersdijk, The Netherlands. After identifying the new variety as a potentially interesting selection, the inventor continued confidential testing and propagation of 'Dragonrayo' assessing stability of the unique characteristics of this variety.
Asexual reproduction of the new cultivar 'Dragonrayo' was first performed at the commercial greenhouse of the inventor in Honselersdijk, The Netherlands by vegetative cuttings in 2006. Access to all plants was restricted, as plants were kept in a locked greenhouse not open to the public. Through subsequent propagation by vegetative cuttings, multiple generations have been reproduced, which have shown that the unique features of this cultivar are stable and reproduced true to type.


A low-power data conversion system for converting a serial digital data input signal (DIN) to an analog output signal (Vout) by generating the serial digital data input signal (DIN) at a first sample rate (fsin) in a burst mode, wherein the sampling frequency of the serial digital data input signal (DIN) has a predetermined ratio to the frequency of an external reference clock signal (SLEEPCLK or WCLK). The serial digital data input signal (DIN) is converted into parallel format. A FIFO system temporarily stores a predetermined number of samples (Din) of the parallel format digital data input signal. The samples (Din) have a first sample rate (fsin). The samples (Din) are converted to an analog output signal (Vout).

The present invention relates generally to low power audio DAC systems, for example, audio DAC systems adapted to be used in portable audio systems to play back digital audio data in analog format (for example by decoding it from compressed MP3 format or by receiving it in PCM (pulse code modulation) format supplied by a digital signal processor), while minimizing power consumption. The invention also relates more particularly to such audio DAC systems which include a sample rate converter in an audio digital to analog converter ("audio DAC") wherein the audio DAC is not required to be locked in synchronization with the sampling rate of the audio input data.
Audio digital to analog converters (DAC) are widely used in various applications, such as cell phones and MP3 players, wherein the digital audio samples are played back by means of speakers and/or headphones. Because audio signals are increasingly stored and processed in digital format, the number of applications of audio DACs are increasing.
Normally, a digital signal processor performs a decoding if the original audio data are compressed, and then processes and transfers the decoded and processed audio data to the audio DAC continuously at the audio data sampling rate. The audio DAC receives the audio data and plays it at a rate derived from the externally provided operating clock rate. Typically, the operating clock rate is 512, 256 or 128 times the audio sampling rate. The DSP (digital signal processor) can operate very fast, so it does not have to run continuously to accomplish the required decoding and processing tasks. Unfortunately, the continuous audio data transfer from the DSP to the audio DACs of the prior art requires that the DSP remain in a "powered up" mode even though there are not any other actions presently required to be performed by the DSP. Under these conditions, circuitry and associated software not related to the audio data transfer from the DSP continue to consume and therefore waste power.
An audio DAC ordinarily consists of two parts, including a digital processing circuit which interpolates (and sometimes performs other processing on) the incoming audio data. The interpolated data may be processed by a digital delta-sigma modulator, the output of which typically is provided as an input to an analog DAC. In conventional audio DACs, the audio data is interpolated by multi-stage interpolation filters and then is fed into a digital delta-sigma modulator. The digital delta-sigma modulator is used to reduce the audio data word width and push quantization noise out of the audio band to reduce distortion caused by nonlinearity of an analog DAC section of the audio DAC. The reduced width audio data words are converted into analog signals by the analog DAC.
Various analog audio sources often are sampled at various different sample frequencies and the sampled signals then are digitized to produce various audio signals which can be readily edited, reproduced and processed easily in digital format without introducing nearly as much distortion and noise as would be introduced if the same editing, reproducing and processing were to be performed on the same audio signals in analog format.
Ordinarily, audio DACs operate at clock signal rates that are locked in synchronization with the digital audio input sampling rates, in order to avoid pitch shift artifacts. The effect of the pitch shift artifacts is that the tone at the analog output is not exactly at the frequency it is supposed to be. For example, if the DAC is operating at 48.5 kHz while playing a 1 kHz tone recorded at 48 kHz, the tone at the DAC output will be 1.01 kHz instead of 1 kHz. There are several typical sampling rates for digital audio data, so clock signals related to those typical sampling rates need to be available for clocking the audio DAC to enable it to "play back" the received digital audio at different audio sampling rates. To achieve high quality audio output, the clock signals being utilized need to have low jitter. The jitter of the DAC clock has an FM modulation effect on the audio signals. For example, if the jitter is sinusoidal and the playback audio signal is a tone, there will be two "side tones" at each side of the main audio tone, and the distance of each side tone to the main audio tone is equal to the jitter frequency. In some applications, it is difficult to provide analog DAC clock signals that meet the foregoing requirements. That is, a low jitter clock signal which has a frequency related to the audio sampling rate is not conveniently available in some applications.
Normally, in the prior art a clock signal having a frequency that is directly related to the sampling rate is needed. Otherwise, a PLL (phase locked loop) must be used to generate a sampling-rate-related clock signal from a clock signal that is not directly related to the sampling rate. However, it would be highly desirable for some audio DAC applications that any reference signal, such as the output of a free-running oscillator, could be used for controlling the operating rate of the analog DAC section of an audio DAC.
Sample rate converters are necessary for interfacing between devices receiving and/or producing digital signals having different sample rates, in order to avoid audio sample dropping or sample repeating which results in highly undesirable audible "popping" or "clicking" sounds. Even for two devices that receive and/or produce digital signals having the same nominal sample rates but which are based on two asynchronous clocks, it is necessary to use an asynchronous sample rate converter to accomplish interfacing between the two devices in order to avoid audio sample dropping or repeating.
In asynchronous sample rate converters it is not necessary that the sample rate of the output signal be synchronized with the sample rate of the input signal. Asynchronous sample rate converters each receive a stream of input samples, process them, and produce output samples when requested, and can be used to convert between any two sample rates irrespective of whether the ratio of the two sample rates is an integer or is a rational number, and irrespective of whether the two sample rates are synchronized.
Because of this feature, an asynchronous sample rate converter can decouple a first digital audio device producing a digital output having a first sample rate from a second digital audio device which is intended to receive the output of the first digital audio device and sample it at a second sample rate. For example, the sample rate of an audio source device might be 48 kHz, and the desired sample rate for an audio destination device might also be 48 kHz, but the clock signals of the audio source device and the audio destination device might be independent and therefore asynchronous. In this case, even though the nominal sample rates both are 48 kHz, a very small drift or difference between the frequencies of the two above-mentioned 48 kHz clock signals will accumulate and cause the above-mentioned undesirable/annoying sample dropping or sample repeating if a synchronous sample rate converter is used.
One asynchronous sample rate converter is disclosed in the assignee's co-pending patent application "ASYNCHRONOUS SAMPLE RATE CONVERTER AND METHOD" Ser. No. 10/325,202, filed Dec. 20, 2002 by Xianggang Yu, Terry L. Sculley and Jung-Kuei Chang, Published Jun. 24, 2004 as Publication No. US 2004/0120361 A1.
There is an unmet need for a way to reduce power consumption of a system including an audio DAC system and a host processor such as a DSP.
There also is an unmet need for a way to avoid the need to continuously maintain a DSP of a system including an audio DAC system and the DSP in a powered up mode.
There also is an unmet need for a way to provide improved flexibility in the transfer of audio data from a DSP to an audio DAC system.

Low-power high-performance audio DAC system including internal oscillator, FIFO memory, and ASRC