The invention relates to a compound of formula (I)

The present invention relates to novel compounds of formula I
wherein R1, R2, R3, R4, R5,R6,R8, R10 and n are as defined below. The compounds of formula I inhibit transcriptase, have a cytostatic action and are particularly suitable for treating tumors. The compounds of formula I can be obtained by growing Actinomycetales species HAG 003959, DSM 12931, in a culture medium. Accordingly, the invention relates to a process for preparing the compounds of formula I the use of the compounds for preparing a pharmaceutical for the treatment of malignant disorders and of diseases which can be treated by inhibiting transcriptase, and to pharmaceutical preparations comprising at least one compound of formula I.
Cancer is a disease of humans and animals which is in most cases fatal and which is generally caused by the uncontrolled growth of endogenous cells. Cancer is the term used for the formation of malignant tumors (malignancy), of neoplasms (tumors or carcinomas) or for the malignant degeneration and dysmaturity of white blood cells (leukemia). Cancer or tumor cells are generally formed by transformation of endogenous cells. The malignancy of the cancer cell expresses itself in the autonomy of growth, i.e. its capability of growing uninhibitedly and without integration into the organ system and infiltrating, with destruction of tissue. A sure sign of malignancy is the formation of metastases far from the tumor after hematogenic or lymphogenic spreading of tumor cells. Cancer is one of the most frequent causes of death in humans, and there is therefore a great demand for methods and agents for curing or treating malignant degenerations.
In addition to the radical approach of surgical removal of the tumor, the options for therapy of malignant tumors include radiotherapy with X-rays, xcex1-, xcex2-, xcex3-rays, immunotherapy and chemotherapy. As yet, the use of immunotherapy is limited. Chemotherapy of tumors is understood as meaning administration of cell toxins (cytostatics) for the treatment of tumors and remaining tumor cells generally after local surgical treatment or irradiation. These substances intervene specifically in certain processes of cell division, so that tissues having a high proportion of dividing cells, such as the rapidly growing tumor tissue, react sensitively. The agents used are alkylating compounds, such as, for example, cyclophosphamide (The Merck Index, 12th Ed. page 463), antimetabolites, such as methotrexate (The Merck Index, 12th Ed. page 1025), alkaloids, such as vincristine (The Merck Index, 12th Ed. page 1704) and antibiotics, such as daunomycin (The Merck Index, 12th Ed. page 479), and adriamycin (The Merck Index, 12th Ed. pages 581-582). However, owing to massive side-effects, all these agents have significant disadvantages, so that the death of the diseased person can, in many cases, only be delayed, but not prevented. Furthermore, degenerated (cancer) cells become resistant to the agents used; in this case, the conventional pharmaceuticals no longer have any cytostatic action, but they are toxic, owing to the side-effects. Furthermore, it has been found that a combined and/or sequential use of cytostatics exceeds the activity of an individual cytostatic (monotherapy), and it is therefore possible that the considerable side-effects in polychemotherapy are non-additive. For all these reasons, novel chemotherapeutics are urgently required and thus investigated world-wide.
Surprisingly, it has been found that the microorganism strain Actinomycetales species HAG 003959, DSM 12931, is capable of producing highly effective novel cytostatics which inhibit cell growth even at very low concentrations. Hereinbelow, the novel compounds are referred to as pluraflavins, and they form, together with pluraflavin derivatives, part of the subject matter of the invention. The pluraflavins are antibiotics which comprise a p-quinoid ring skeleton and various sugar building blocks. They inhibit transcription by intercalation of nucleic acid double strands and, if appropriate, additional alkylation. The ring skeleton was described for the first time by S. Kondo et al. in Journal of Antibiotics, volume 30, pages 1143-1145, 1977, as a part of pluramycin. Later, this ring skeleton was found in a plurality of antibiotics; in addition to pluramycin and neopluramycin, the compounds saptomycines (N. Abe et al. J. Antibiotics, 46, 1536-1549, 1993), ankinomycin (Y. Sato et al. J. Antibiotics 42, 149, 1989), kidamycin (N. Kanda et al. J. Antibiotics, 24, 599, 1971), hedamycin (U. Sequin et al. Tetrahedron, 34, 761, 1978) and the altromycines (G. M. Brill et al. J. Antibiotics, 43, 229-237, 1990) have been described as structurally related compounds. The prior art substances often have disadvantages which manifest themselves in an unsatisfactory efficacy, high toxicity and/or undesirable side-effects.
Accordingly, the present invention relates to compounds of formula (l)
wherein
R1 is a sugar,
R2 is xe2x80x94COOH or xe2x80x94CH2xe2x80x94Oxe2x80x94(R7)m, wherein R7 is a sugar group,
R3 is chosen from epoxide-comprising groups,
C1-C6-alkyl groups, and C2-C6-alkenyl groups, wherein said alkyl and alkenyl groups are optionally substituted with at least one OH group,
R5 is chosen from H, C1-C6-alkyl, C2-C6-alkenyl and C2-C6-alkynyl,
R4, R6, R8 and R10, are each independently chosen from H, C1-C6-alkyl, C2-C6xe2x80x94alkenyl, C2-C6xe2x80x94alkynyl, xe2x80x94X2H, and -X2R12, or
R4 and R6 together and/or R8 and R10 together are =X2,
X2 is O, NH, N-C1-C6xe2x80x94alkyl, N-C2-C6xe2x80x94alkenyl, N-C2-C6-alkynyl or S,
R12 is C1-C6xe2x80x94alkyl, C2-C6-alkenyl, C2-C6-alkynyl, aryl or acyl, and
m and n, independently of one another, are 1 or 2,
in all their stereochemical forms and mixtures of these forms in any ratio, and their physiologically acceptable salts and derivatives.
In formula (I)
C1-C6-alkyl is a straight-chain or branched alkyl having from 1 to 6 carbon atoms, for example, methyl, ethyl, isopropyl, tert-butyl and hexyl,
C2-C6-alkenyl is a straight-chain or branched alkenyl having from 2 to 6 carbon atoms, for example, allyl, crotyl and pentenyl, and
C2-C6-alkynyl is a straight-chain or branched alkynyl having from 2 to 6 carbon atoms, for example, propynyl, butynyl and pentynyl.
Aryl is an aromatic ring structure, for example, phenyl, benzyl or 1- or 2-naphthyl. Aryl may be optionally substituted, for example by halogen, such as chlorine, bromine, fluorine, by alkyl having 1-4 carbon atoms, for example, methyl, by hydroxyl, by alkoxy having 1-4 carbon atoms, for example methoxy, and/or by trifluoromethyl.
Acyl can be aliphatic or aromatic acyl groups. The aliphatic acyl has 1-7 carbon atoms, for example 1-4 carbon atoms, such as, formyl, acetyl, propionyl, butyryl, hexanoyl, acryloyl, crotonoyl, propioloyl, which can be substituted further, for example by halogen, such as chlorine, bromine, fluorine, by amino, and/or by alkylamino having 1-4 carbon atoms, such as methyl- or ethylamino groups. Aromatic acyl can, for example, be benzoyl or naphthoyl, which can also be substituted further, for example by halogen, such as chlorine, bromine, fluorine, by alkyl having 1-4 carbon atoms, for example methyl, by hydroxyl, by amino groups, such as, example ethylamino, or by alkoxy groups having 1-7 carbon atoms, such as 1-4 carbon atoms, for example methoxy.
The sugar (R1R7) is a monosaccharide (n=1) or a disaccharide (n=2), where two monosaccharides are linked glycosidically. The monosaccharide can be a hexose (C6H12O6), for example an aldohexose, such as, D-(+)-glucose, D-(+)-mannose or D-(+)-galactose. The monosaccharide can be mono-, di- or tri-substituted, independently of one another, by H, OH, NH2, NH(alkyl), N(alkyl)2, alkyl and alkoxy, where the H and/or OH of the monosaccharide can be optionally replaced by substituents. The term xe2x80x9csugarxe2x80x9d, as used herein, includes amino sugars. An amino sugar is a monosaccharide or disaccharide optionally substituted as described wherein at least one OH- or H-group of the mono- or disaccharide is replaced by an amino group such as NH2, NH(alkyl) or N(alkyl)2.
In one embodiment, m is 1.
R7 may be an aminosugar group of formula (II)
wherein
R13, R14, R16, R18, R20, R22, R24, R26 and R28, are each independently chosen from H, OH, NH2, NHalkyl, N(alkyl)2 and alkoxy, where alkyl and alkoxy have from 1 to 4 carbon atoms.
Examples of C1-C4-alkyl are, for example, methyl, ethyl, propyl, isobutyl and butyl, in particular methyl, and examples of C1-C4-alkoxy are, for example, methoxy, ethoxy, isopropoxy or butoxy, in particular methoxy.
R7 can be an aminosugar of formula (IIA):
R1 may also be an aminosugar. In one embodiment, n is 2.
R1 may be a group of formula (III)
wherein R30 to R60, independently of one another, are H, OH NH2, NHalkyl, N(alkyl)2, or alkoxy, wherein alkyl is a C1-C4 group, such as, methyl, ethyl, propyl, isobutyl and butyl, in particular methyl, and O-alkyl is C1-C4-alkoxy, for example, methoxy, ethoxy, isopropoxy or butoxy, in particular methoxy.
R1 in one embodiment, had the formula (IIIA)
R3 can be an epoxide-comprising group. The epoxide-comprising group can be a straight-chain or branched alkyl or alkenyl group having from 2 to 12 carbon atoms, such as from 2 to 6 carbon atoms, which comprise one or two epoxide rings (oxiranes). Possible examples are:
Other than an epoxide-comprising group, R3 can be a straight-chain or branched alkyl having from 1 to 12 carbon atoms, such as 1 to 6 carbon atoms, such as, for example, methyl, ethyl, isopropyl, tert-butyl, hexyl, and also, for example, octyl, dodecyl, or a straight-chain or branched alkenyl having from 2 to 12 carbon atoms, such as 2 to 6 carbon atoms, for example, allyl, crotyl, pentenyl, and also dodecenyl, where these alkyl or alkenyl groups can also be mono- or polysubstituted, for example by hydroxyl.
The invention accordingly relates to pluraflavin A of formula (IA)
to pluraflavin B of formula (IB)
and to pluraflavin E of formula (IE)
wherein hexose I is a 2,6-dideoxyaldohexose;
hexose II is a 2,3,6-trideoxy-3-dimethylaminohexose and
hexose III is a 2,3,6-trideoxy-3-amino-3-methylaldohexose, in all their stereochemical forms and mixtures of these forms in any ratio, and their physiologically acceptable salts and derivatives.
In one embodiment, the compounds are chosen from formulae (IA), (IB) and (IE),
wherein
hexose I is oliose,
hexose II is rhodosamine and
hexose III is 3-epi-vancosamine.
According to the invention, the compounds of formula I are obtainable by cultivation, for example by fermentation, of the Actinomycetales species HAG 003959, DSM 12931, or its variants or mutants, under suitable conditions in a culture medium, until at least one of the pluraflavins of formula (IA), (IB) and/or (IE) is present in the culture medium. The pluraflavins may be subsequently isolated from the culture medium and purified and, if appropriate, converted into derivatives and/or into their physiologically acceptable salts.
The invention furthermore relates to a process for preparing a compound of formula I which comprises cultivating, for example by fermenting, the microorganism Actinomycetales species HAG 003959, DSM 12931, or its variants or mutants, under suitable conditions in a culture medium, until at least one of the pluraflavins of formula (IA), (IB) and/or (IE) is present in the culture medium, isolating at least one of the pluraflavins from the culture medium and, if appropriate, converting into derivatives and/or physiologically acceptable salts.
The strain HAG 003959, DSM 12931, its mutants and/or variants are in one embodiment, cultivated in a nutrient solution (also referred to as culture medium) comprising at least one source of carbon atoms and at least one source of nitrogen atoms and the customary inorganic salts, until at least one novel pluraflavin is present in the culture medium; the pluraflavins may be subsequently isolated from the culture medium and, if appropriate, separated into the individual active components.
The cultivation can be carried out under aerobic conditions. The cultivation can be carried out at a temperature ranging from 18 to 35xc2x0 C. and at a pH ranging from 6 to 8.
In the literature, a large number of reactions for chemical derivatization of quinones have been described. Accordingly, the derivatization of the quinone forms of the present compounds can be carried out using chemical reactions which are known per se. A reduction to the hydroquinone forms of the compounds can, for example, be achieved catalytically with hydrogen, or with metal hydrides, such as aluminum hydrides or boron hydrides. A further suitable example is the conversion of quinones with hydroxylamine or with its derivatives into oximes which for their part can be further chemically converted.
The invention accordingly relates to a compound of formula (IV):
wherein R1, R2, R3 and n are as defined above, in any of its stereochemical forms and mixtures of these forms in any ratio, and a physiologically acceptable salt or derivative thereof.
The pluraflavin derivatives of formulae (IVA), (IVB) and (IVE) (below), are derived from the pluraflavins of formulae (IA), (IB) and (IE), respectively, and they also form part of this invention.
The invention furthermore relates to: a compound of formula (IVA)
a compound of formula (IVB)
and a compound of formula (IVE)
in any of their stereochemical forms and mixtures of these forms in any ratio, and a physiologically acceptable salt or derivative thereof.
Hereinbelow, the invention is described in detail, for example in at least one embodiment.
The pluraflavins according to the invention are produced by Actinomycetales species, in one embodiment, by Actinomycetales spec HAG 003959, DSM 12931. The Actinomycetales species HAG 003959, DSM 12931, has a beige-red mycelium and can be identified by conidiophores which are typical for actinomycetes.
A taxonomic examination of the microorganism Actinomycetales spec HAG 003959, DSM 12931, gave the following result of the determination of the strain: the diagnostically important fatty acid analysis by gas chromatography showed high proportions of:
Anteiso 15:0 fatty acid,
Iso 16:0 fatty acid (isopalmitic acid),
Iso 17:0 fatty acid (isomargaric acid),
Anteiso 17:0 fatty acid (anteisomargaric acid) and
cis[9] 18:1 fatty acid (oleic acid), in addition to lower concentrations of other fatty acids.
This fatty acid composition profile permits Actinomycetales HAG13 003959 (DSM 12931) to be assigned taxonomically to the genus Saccharothrix.
An isolate of the microorganism was deposited at the Deutschen Sammlung von Mikroorganismen und Zelikulturen GmbH, MascheroderWeg 1B, D 38124 Braunschweig, Germany, according to the rules of the Budapest Convention on Jul. 16, 1999 under the following number: Actinomycetales species HAG 003959, DSM 12931.
Instead of the strain Actinomycetales species HAG 003959, DSM 12931, it is also possible to use its mutants and variants which synthesize at least one compounds of the pluraflavins according to the invention. Such mutants can be produced in a manner known per se by physical means, for example irradiation, e.g. with ultraviolet or X-rays, or chemical mutagens, such as, for example, ethyl methanesulfonate (EMS), 2-hydroxy-4-methoxybenzophenone (MOB) or N-methyl-Nxe2x80x2-nitro-N-nitrosoguanidine (MNNG).
The process according to the invention can be used for fermentation on a laboratory scale (milliliter to liter range) or on an industrial scale (cubic meter scale). Unless indicated otherwise, all percentages are based on weight. In the case of liquids, mixing ratios are based on the volume, unless stated otherwise.
In one embodiment, sources of carbon atoms for aerobic fermentation are assimilable carbohydrates and sugar alcohols, such as glucose, lactose, sucrose or D-mannitol, and hydrocarbon-comprising natural products, such as, for example, malt extract. Suitable sources of nitrogen atoms for cultivation are: amino acids, peptides and proteins and their degradation products, such as peptones or tryptones, furthermore meat extracts, yeast extracts, ground seeds, for example of maize, wheat, beans, soya or cotton, distillation residues of alcohol production, meat meals or yeast extracts, but also ammonium salts and nitrates. Inorganic salts contained in the nutrient solution can, for example, be chlorides, carbonates, sulfates or phosphates of the alkali metals or alkaline earth metals, iron, zinc, cobalt and manganese.
The formation of the pluraflavins according to the invention proceeds in a culture medium which comprises about 0.1 to 5%, such as 0.3 to 2%, of glucose and 0.2 to 5%, such as 0.5 to 3%, of soya meal and 0.05 to 2%, such as 0.2 to 1.0 g/l of corn steep and 0.05 to 1.0 g/l, such as 0.1 to 0.5%, of calcium carbonate and 0.05 to 1.0 g/l, such as 0.1 to 1.0 g/l, of sodium chloride. The percentages are in each case based on the weight of the entire culture medium.
In the culture medium, Actinomycetales species HAG 003959, DSM 12931, produces a mixture of pluraflavins. Depending on the composition of the culture medium, the proportion of at least one of the pluraflavins according to the invention may vary. Furthermore, via the composition of the medium, it is possible to control the synthesis of individual pluraflavins, so that one or even more of the pluraflavins are not produced at all by the microorganism, or in an amount below the detection limit.
In one embodiment, the culture comprises one detectable pluraflavin. In further embodiments the pluraflavins A, B or E are formed.
In addition to the pluraflavins A, B and E (compounds of formula (IA), (IB) and (IE), respectively), other related compounds, which differ from the compounds represented in the formulae (IA), (IB) and (IE) in that they are glycosylated differently, are also formed in the culture medium of Actinomycetales species HAG 003959, DSM 12931. Thus, as by-product, a further pluraflavin (pluraflavin C) with a molecular weight of 974 Da and a degradation product of pluraflavin A, molecular weight 692.77, C37H44N2O11, were detected. In the latter compound, hexose I is missing; under acidic conditions, the 2,6-dideoxyaldohexose can be hydrolytically cleaved off from pluraflavin A.
The microorganism is cultivated aerobically, i.e., for example, submersed with shaking or stirring in shaker flasks or fermenters, if appropriate with introduction of air or oxygen. It can be carried out in a temperature range from approximately 18 to 35xc2x0 C., such as from approximately 25 to 32xc2x0 C., including from 27 to 30xc2x0 C. The pH generally should range from 6 to 8, such as from 6.5 to 7.5. Under these conditions, the microorganism is generally cultivated over a period ranging from 24 to 300 hours, such as from 36 to 140 hours.
Cultivation is advantageously carried out in several stages, i.e. at least one preculture is first prepared in a liquid nutrient medium, which is then inoculated into the actual production medium, the main culture, for example in the volume ratio 1:10. The preculture is obtained, for example, by inoculating a mycelium into a nutrient solution and allowing it to grow for approximately 36 to 120 hours, such as for 48 to 96 hours. The mycelium can be obtained, for example, by allowing the strain to grow for about 3 to 40 days, such as for 4 to 10 days, on a solid or liquid nutrient medium, for example malt-yeast agar or oatmeal agar.
The progress of the fermentation can be monitored by the pH of the cultures or the mycelium volume, and also by chromatographic methods, such as, for example, thin-layer chromatography or high pressure liquid chromatography or testing the biological activity. The pluraflavins according to the invention may be found in both the mycelium and in the culture filtrate. The isolation process described below generally serves to purify the pluraflavins according to the invention, such as to purify the pluraflavins A, B and E.
Isolation and/or purification of the pluraflavins according to the invention from the culture medium is carried out by known methods, taking into account the chemical, physical and biological properties of the natural products. To test the pluraflavin concentration in the culture medium or in the individual isolation stages, it is possible to use thin-layer chromatography, for example on silica gel using chloroform/methanol/-glacial acetic acid/water mixtures (for example in the ratio 8:1:1:0.2) as mobile phase, or HPLC. In the thin-layer chromatographic separation, detection can be carried out, for example, using staining reagents, such as a-naphthol/sulfuric acid, where the amount of the substance formed is expediently compared to a calibration solution.
According to the invention, pluraflavins may be isolated from either mycelium or culture medium. Generally, the mycelium is initially separated off from the culture medium by the customary methods, and the pluraflavins are subsequently extracted from the cell material using an optionally water-miscible organic solvent. The organic-solvent phase contains pluraflavins according to the invention; if appropriate, they are concentrated under reduced pressure and purified further as described below.
If appropriate, the culture filtrate is combined with the concentrate of the mycelium extract and extracted with a suitable water-immiscible organic solvent, for example with n-butanol. The organic phase is then separated off and, if appropriate, concentrated under reduced pressure. To defat the product of value, the concentrate can be diluted with an nonpolar solvent wherein the pluraflavins according to the invention are only sparingly soluble, such as, for example, with hexane, petroleum ether, diethyl ether. This causes the pluraflavins to precipitate, and the lipophilic impurities remain dissolved and are removed by customary solid-liquid phase separation. The precipitate, which contains all pluraflavins to be isolated, is dissolved in {fraction (1/30)} of the original volume of water/methanol. The precipitate is dissolved completely and is lyophilized. The lyophilizate, which is referred to as crude product hereinbelow, comprises 0.5 to 50% of pluraflavin and is used for further isolation.
The further purification of one or more of the pluraflavins according to the invention is carried out by chromatography on suitable materials, such as on molecular sieves, on normal phase carriers, such as, for example, silica gel, alumina, on ion exchangers or on adsorber resins and/or on reversed phase mediums (RP). With the aid of this chromatography, the pluraflavins are separated. The chromatography of the pluraflavins is carried out using buffered aqueous solutions or mixtures of aqueous and organic solutions.
Mixtures of aqueous or organic solutions are understood as meaning all water-miscible organic solvents, such as methanol, propanol and acetonitrile, in a concentration ranging from 10 to 80% solvent, for example from 40 to 60% solvent, or else all buffered aqueous solutions which are miscible with organic solvents. The buffers to be used may be the same as indicated above.
Separation of the pluraflavins based on their differing polarity may be carried out with the aid of reversed phase chromatography, for example on MCI(copyright) (adsorber resin from Mitsubishi, Japan) or Amberlite XAD(copyright) (TOSOHAAS), on further hydrophobic materials, such as, for example, on RP-8 or RP-18 phases. Moreover, separation can be carried out with the aid of normal phase chromatography, for example on silica gel, alumina and the like.
The chromatography of the pluraflavins may be carried out using buffered or acidified aqueous solutions or mixtures of aqueous solutions with alcohols or other water-miscible organic solvents. The organic solvent used can be propanol and acetonitrile.
Buffered or acidified aqueous solutions are understood as meaning, for example, water, phosphate buffer, ammonium acetate, citrate buffer in a concentration from 1 mM to 0.5 M, and also formic acid, acetic acid, trifluoroacetic acid or all commercial acids known to the person skilled in the art, for example, in a concentration ranging from 0.01 to 3%, such as from 0.1%.
Chromatography can be carried out using a gradient starting with 100% aqueous buffer and ending with 100% solvent; for example a linear gradient ranging from 10 to 50% using 2-propanol or acetonitrile.
Alternatively, it is also possible to carry out gel chromatography or chromatography on hydrophobic phases.
Gel chromatography can be carried out on polyacrylamide or mixed polymer gels, such as, for example, Biogel-P 2(copyright) (Biorad), Fractogel TSK HW 40(copyright) (Merck, Germany or Toso Haas, USA) or on Sephadex(copyright) (Pharmacia, Uppsala, Sweden).
The order of the chromatographies mentioned above can be reversed.
A further, highly effective purification step for pluraflavins is crystallization. The pluraflavins crystallize from solutions in organic solvents and from mixtures of water with organic solvents. Crystallization can be carried out in a manner known per se, for example by concentration or cooling of saturated pluraflavin solutions.
The pluraflavins according to the invention are stable in the solid state and in solutions having a pH ranging from 3 to 8, for example frompH 4 to 6, and they can therefore be incorporated into customary pharmaceutical preparations.
The pluraflavins of formula (I) and the derivatives derived therefrom can be converted by methods known to the person skilled in the art into the corresponding physiologically acceptable salts.
Physiologically acceptable salts of compounds of formula (I) are understood as meaning both their organic and inorganic salts, such as are described in Remington""s Pharmaceutical Sciences (17th edition, page 1418 (1985)). Based on the physical and chemical stability and the solubility, sodium, potassium, calcium and ammonium salts, inter alia, are possible embodiments of acidic groups; salts of hydrochloric acid, sulfuric acid, phosphoric acid or of carboxylic acids or sulfonic acids, such as, for example, acetic acid, citric acid, benzoic acid, maleic acid, fumaric acid, tartaric acid and p-toluenesulfonic acid, inter alia, are possible embodiments of basic groups.
The invention furthermore embraces chemical equivalents, herein also referred to as xe2x80x9cderivativesxe2x80x9d, of the compounds of formula (I) which have the same or substantially the same activity or which can be converted into the compound according to the invention. The equivalents mentioned include, for example, esters and ethers, complexes and also reduction products of the compounds according to the invention.
Esters and ether derivatives and reduction products can be prepared by processes described in the literature, for example in xe2x80x9cAdvanced Organic Synthesisxe2x80x9d, 4th edition, J. March, John Wiley and Sons, 1992. The carboxy group (formula IE, IVE) and hydroxy groups of the compounds of the formula (I) can be converted to an ester, such as C1-C4 alkyl ester, or ether group, for example, acetals and ketals of the hydroxy groups.
Stable complexes of the compounds of the formula (I) may be formed with physiologically acceptable inorganic cations, such as calcium or magnesium.
The present invention embraces all stereoisomeric forms of the compounds of formula (I). Centers of asymmetry of the compounds of formulae (IA), (IB) and (IE) can, independently of one another, in each case may have the S configuration or the R configuration. The oxiranes of the epoxide-comprising group can be in any position; for example, oxiranes which incorporate the carbon atoms 2xe2x80x2 and 3xe2x80x2. The invention includes all possible enantiomers and diastereomers, and also mixtures of at least two stereoisomeric forms, for example mixtures of enantiomers and/or diastereomers, in any ratio. Thus, the invention provides enantiomers in enantiomerically pure form, both as laevorotatory and as dextrorotatory antipodes, R and S configurations, in the form of racemates and in the form of mixtures of the two enantiomers in any ratio. If there is a cis/trans isomerism, the invention provides both the cis form and the trans form and mixtures of these forms in any ratio.
On account of their useful pharmacological properties, the compounds according to the invention are suitable for use as pharmaceuticals in human and/or veterinary medicine. They have antibiotic activity and, in addition to the antibacterial action, antimycotic, i.e. fungi-inhibiting, including phytopathogenic fungi, antiprotozoic and antiparasitic properties.
The compounds according to the invention can be used for cancerous diseases, for example as chemotherapeutics. Owing to their cytostatic properties, such as their potent antitumor activity, and an antimicrobial action, they can be used, for example, as cytostatics for malignant degenerations in animals and humans.
In the case of tumor cells which have developed resistances to conventional agents, only novel agents have a therapeutically adequate effect. Thus, the pluraflavins according to the invention and derivatives thereof of formula (I) have a potentially excellent activity even against these problem cell types.
The invention also relates to pharmaceutical preparations which comprise at least one of the pluraflavins according to the invention and/or derivatives thereof. Plurflavins may be used in a mixture with at least one suitable auxiliary or excipient. The excipients used for humans can be all pharmacologically acceptable excipients and/or auxiliaries.
The invention also relates to a process for preparing a pharmaceutical according to the invention which comprises bringing at least one compound according to the invention into a suitable administration form using a pharmaceutically suitable and physiologically acceptable excipient and, if appropriate, further suitable active compounds, additives or auxiliaries.
The pharmaceuticals according to the invention are generally administered orally, topically or parenterally, but rectal administration is also possible. Suitable solid or liquid pharmaceutical preparation forms are, for example, granules, powders, tablets, coated tablets, (micro)capsules, suppositories, syrups, emulsions, suspensions, aerosols, drops or injectable solutions in ampoule form, and preparations having a protracted release of active compound, in whose preparation excipients and additives and/or auxiliaries, such as disintegrants, binders, coating agents, swelling agents, glidants or lubricants, flavorings, sweeteners or solubilizers are customarily used. Frequently used excipients or auxiliaries which may be mentioned are, for example, magnesium carbonate, titanium dioxide, lactose, mannitol and other sugars, talc, lactoprotein, gelatin, starch, vitamins, cellulose and its derivatives, animal or vegetable oils, polyethylene glycols and solvents such as, for example, sterile water, alcohols, glycerol and polyhydric alcohols.
If appropriate, the dose units can be microencapsulated for oral administration to delay the release or to extend the release over a relatively long period of time, such as, for example, by coating or embedding the particulate active compound into suitable polymers, waxes or the like.
The pharmaceutical preparations may be produced and administered in dose units, each unit comprising as active ingredient a certain dose of at least one compound of the pluraflavins according to the invention and/or derivatives thereof. In the case of solid dose units such as tablets, capsules and suppositories, this dose can be up to approximately 200 mg, but can be approximately 0.1 to 100 mg, and in the case of solutions for injection in ampoule form up to about 200 mg, but can be about 0.1 to 100 mg, per day.
The daily dose to be administered depends on the bodyweight, age, sex and condition of the mammalian subject. However, higher or lower daily doses may also be called for. The daily dose can either be administered by being given on one occasion in the form of a single dose unit or in the form of several smaller dose units, or else being given on several occasions, at predetermined intervals, in the form of subdivided doses.
The invention is illustrated further in the examples which follow. Percentages are based on weight. In the case of liquids, mixing ratios are based on volume, unless stated otherwise.
The following are illustrative examples of the present invention but not limitative of the scope thereof.

Pluraflavins and derivatives thereof, process for their preparation and use thereof

Abstract: wherein R1 is a sugar; R2 is xe2x80x94CH2xe2x80x94Oxe2x80x94(R7)m, R7 representing a sugar, or is xe2x80x94COOH; R3 is an epoxide-comprising group, or is C1-C6-alkyl or C2-C6-alkenyl, unsubstituted or substituted by at least one OH; R5 is H, C1-C6-alkyl, C2-C6-alkenyl or C2-C6-alkynyl; R4R6, R8 and R10 independently of one another are H; C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, xe2x80x94X2H, or xe2x80x94X2R12, or R4 and R6 together and/or R8 and R10 together are =X2; X2 is O, NH, Nxe2x80x94C1-C6-alkyl, Nxe2x80x94C2-C6-alkenyl, N-C2-C6-alkynyl or S; R12 is C1-C6-alkyl, C2-C6xe2x80x94alkenyl, C2-C6-alkynyl, aryl or acyl; and m and n are 1 or 2; in any of its stereochemical forms and mixtures of these forms in any ratio, and a physiologically acceptable salt or derivative thereof. The compounds are obtainable from a culture of the microorganism Actinomycetales species HAG 003959, DSM 12931, by fermentation. Accordingly, the invention relates to a process for their preparation and to the use of the compounds as pharmaceuticals, for example as antitumor agents.


A portable device, for example an offender monitor, can utilize a GPS receiver or other location detector to provide locational information for the device. The portable device can communicate over a cellular network, for example using a radio to transmit location readings over the network. The location detector and the radio can draw power from an onboard battery. The portable device can operate in at least two modes. When charge of the battery drops below a threshold, the device can switch from the first mode of operation to the second mode to conserve power and avoid fully depleting the battery.

An offender monitor can utilize a rechargeable onboard battery for power. However, if the battery's power is exhausted, a conventional offender monitor may be susceptible to tampering during a window of time before the battery is recharged. Moreover, the offender may have an opportunity to go to an impermissible location or to otherwise perform an impermissible act that would otherwise be detected and reported by the offender monitor.
Accordingly, there are needs in the art for energy management of offender monitors. For example, need exists for a technology to avoid fully depleting battery power of an offender monitor. Need further exists for preventing an offender monitor from providing an offender with a window of time during which tampering or other improper actions may go undetected. A technology addressing one or more such needs, or some related deficiency in the art, would result in benefits that may include improved offender management, for example.

Method and system for energy management of an offender monitor


A hydrogenation method and distillate two-phase hydrogenation reactor in which the size of an upper space of the reactor is greater than that of a lower catalyst bed part. The reactor comprises 2 to 4 catalyst beds. An inner component for gas replenishment and for stripping a liquid-phase stream containing impurities is arranged between at least one adjacent catalyst bed and comprises a separator plate and exhaust pipes. The separator plate is provided with multiple downcomer through holes. The separator plate is connected with a plurality of exhaust pipes. The exhaust pipes are vertically arranged above the separator plate. The top parts of the exhaust pipes are in contact with the lower part of the upper catalyst bed.

With increasingly reinforced environmental consciousness, many countries have limited sulfur content of diesel fuel to a quite low level (10 to 15 μg/g), to reduce the emission of harmful gases, and improve air quality by means of environmental legislation. The sulfur content of diesel fuel was decreased to 15 μg/g in 2006 in USA. The sulfur content of diesel fuel was decreased to 10 μg/g in January, 2003 in Germany. The sulfur content of diesel fuel was decreased to 10 μg/g in 2008 in other countries of European Union (EU) and Japan. The national standard on the urban automotive diesel fuel of China, GB 19147-2009 was formulated according to the Europe's category III standard, which requires the sulfur content to be less than 350 μg/g. In the discharging index of the fifth stage for the automotive gasoline and diesel oil, issued by the State Ministry of Environmental Protection of China, it is required that the sulfur content in the diesel oil should be less than 10 μg/g.
The requirement for the diesel oil in the international market has been increasing constantly. However, the supply amount of high-grade feedstock oil has been decreasing. How to utilize the low-grade feedstock oil to manufacture diesel with ultralow sulfur content to meet the increasing demand has been a big challenge that the refineries have to face. To meet the challenge, on one hand, it needs to resolve the key technological difficulties, and newly construct hydrogenation apparatuses to conduct deep hydrodesulfurization for diesel; on the other hand, it needs to reduce risks and repeated investments in order to guarantee economic benefits. In the traditional hydrogenation process using a fixed bed, it is necessary to transfer hydrogen gas from gas phase to liquid phase, then the reaction between the dissolved hydrogen and sulfur compound occurs at an active centre of catalysts, thereby achieving the desulfuration purpose. During the process, the required volume of hydrogen gas is much greater than that consumed in the hydrogenation reaction. This is because, on one hand, the hydrogenation reaction is a strong exothermic reaction, which, for controlling the reaction temperature, needs a large amount of hydrogen gas and feedstock oil to pass through catalyst beds to bring away reaction heat; on the other hand, in the reaction related to three phases of gas, liquid and solid, maintaining a high hydrogen partial pressure is helpful for the hydrogenation reaction, inhibiting the production of coke and prolonging catalyst life. In addition, the hydrogen not reacted in the reaction may be retransferred to the reactor for reaction after the pressure thereof is increased by passing through a circulating hydrogen compressor. As key equipment for the hydrogenation process, the circulating hydrogen compressor has a high cost in investment and operation. In order to eliminate the circulating hydrogen and the circulating hydrogen compressor so as to reduce the investment cost of the apparatus, a liquid-phase hydrogenation technology was proposed. In the liquid-phase circulation hydrogenation process, the hydrogen gas is premixed with the feedstock oil, so that the hydrogen gas is dissolved in the feedstock oil, then the mixture is introduced into the reactor for reaction. The hydrogen gas needed during the reaction are entirely from the dissolved hydrogen without additional supplement of cool hydrogen. The liquid-phase circulation hydrogenation process possesses advantages of small reactor, low investment cost, easy control of the reaction temperature and the like. However, this liquid-phase circulation hydrogenation process also has one problem, that is, in order to meet the hydrogen gas volume needed in the hydrogenation reaction, it is necessary to use a large amount of circulation oil or additionally add a solvent to dissolve the hydrogen gas, which results in the reduction of the hydrogenation efficiency.
In the conventional fixed-bed hydrogenation process, in order to remove impurities such as sulfur, nitrogen, oxygen, and metal in the raw material or reduce the size of the feedstock oil molecules, it is necessary to carry out a catalytic hydrogenation reaction. In order to control the reaction temperature of a catalyst bed and prevent the catalyst from deactivation by carbon deposition, generally a high hydrogen-oil volume ratio is used, which certainly causes a large amount of surplus hydrogen gas after completion of the hydrogenation reaction. The surplus hydrogen gas is usually pressurized by a circulating hydrogen compressor and then mixed with new hydrogen to be reused as hydrogen feed for reaction. This process can be also defined as a gas-phase circulating, fixed-bed hydrogenation process. For this process, the investment of the circulating hydrogen compressor occupies a relatively high proportion of the whole hydrogenation device cost. The heat exchange system for hydrogen gas has a high energy consumption, so if the hydrogen gas flow in the process of hydrogenation can be reduced and the hydrogen gas circulating system and the circulating hydrogen compressor can be omitted, then the investment of enterprises can be saved, and the cost is reduced for clean fuel production.
Generally, for raw materials containing simple sulfide, the reaction rate of its hydrodesulfurization in a fixed bed hydrogenation reactor is not only related with the concentration of organic sulfide, but also affected by the factors such as wetting situation of the catalyst, concentrations of organic nitride and H2S in the reactor system, and the like. The wetting factor of the catalyst is a measurement of the infiltration degree of the catalyst surface by a liquid reactant under the condition of hydrogenation reaction. The higher is the infiltration degree of the catalyst, the higher the wetting factor of the catalyst will be, that is to say, the higher the effective availability of the catalyst will be. Under the condition that the factors including the catalyst and the like have been defined, the main factor affecting the wetting factor of the catalyst is the flow rate of the liquid in the reactor and the ratio of the flow rate of the gas to that of the liquid. It is generally considered that the increase in the flow rate of the liquid enhances the wetting effect of the catalyst, while the conventional hydrogenation process mostly utilizes a high ratio of hydrogen to oil much more than the need of the reaction, thereby decreasing the wetting effect of the catalyst, and having an adverse influence on the wetting factors. In addition, the investment of the section of hydrogen circulation during petroleum refining occupies a large proportion of the cost of the whole process.
Organic nitride is poison for the hydrogenation catalyst, which has an obvious inhibition effect on the reaction of hydrodenitrification, hydrodesulfurization, and hydrodearomatization. This inhibition effect is mainly caused by the very strong adsorption energy of some nitrides and most of the intermediate reaction product of nitrides to the active centre for hydrogenation reaction of the catalyst, which inhibits occurrence of the other hydrogenation reaction from a viewpoint of competitive adsorption. However, the impurity content of the raw material will be decreased greatly by circulating the hydrogenated product, which helps to exert the performance of the catalyst.
United State patent US20060144756A1 discloses a control system method and apparatus for two phase hydroprocessing. In a continuous liquid phase hydroprocessing, the circulating hydrogen is eliminated, and all the hydrogen needed by the hydrogenation reaction comes from the hydrogen dissolved in the liquid phase without the need of additional hydrogen gas. However, it needs to utilize a solvent or diluent with a high hydrogen solubility to dissolve hydrogen, which influences the subsequent hydrogenation efficiency.
U.S. Pat. No. 6,213,835, U.S. Pat. No. 6,428,686, and CN200680018017.3 discloses a hydrogenation process with dissolving hydrogen in advance, which controls the volume of liquid or the air pressure in the reactor by controlling the hydrogen gas amount contained in liquid feed. But these patents have not totally resolved the problem of removing the detrimental impurity such as H2S and NH3 produced in the hydrorefining reaction process, which results in a continueous accumulation of these impurities in the reactor, thereby greatly reducing the reaction efficiency, and failing to effectively handle raw material with high sulphur and nitrogen content. The above patents do not disclose the specific structure of the reactor, either.
The Chinese patent CN86108622 discloses a hydrorefining process for oil produced by cracking, wherein the volume ratio of hydrogen to oil is 200:1 to 1000:1; the Chinese patent CN93101935.4 discloses a one-stage hydrocracking method for poor-quality feedstock oil, wherein the volume ratio of hydrogen to oil is 1300:1 to 1500:1; the Chinese patent CN94102955.7 discloses a hydrorefining method for DCC gasoline, wherein the volume ratio of hydrogen to oil is 150:1 to 500:1; the Chinese patent CN96109792.2 discloses a method for producing high quality Vaseline by serial hydrogenation process, wherein the volume ratio of hydrogen to oil is 300:1 to 1400:1; and the Chinese patent CN96120125.8 discloses a method for manufacturing white oil by means of direct hydrogenation from naphthenic base straight-run, wherein the volume ratio of hydrogen to oil is 500:1 to 1500:1.
These patents are characterized in a high volume ratio of hydrogen to oil, thus the hydrogen gas circulating step and the circulating hydrogen compressor are necessary.

Distillate two-phase hydrogenation reactor and hydrogenation method


Provided are a decorative sheet having stretchability and heat resistance and an in-mold forming method capable of forming in-mold injection formed products having excellent decorative image. A decorative sheet includes an image layer and an image running prevention region in order on a resin sheet, in which the image layer is a cured image of an ink composition containing (a) a polymerizable compound, (b) a polymerization initiator, and (c) a coloring agent; the image running prevention region is a cured layer of a composition for running prevention containing (a) a polymerizable compound, and (b) a polymerization initiator; and the image running prevention region has superior heat resistance to the image layer, and an injection forming method using the decorative sheet.

1. Field of the Invention
The present invention relates to a decorative sheet and an in-mold forming method.
2. Description of the Related Art
In-mold forming is applied in a large number of fields, and is widely adopted as a method of three-dimensional decorative forming in the fields of consumer electronics, communications, general goods, and the like. In in-mold forming, a decorative sheet is fixed to an inner wall of a hollow portion of an injection forming machine, and integrated forming is performed with an image layer on the decorative sheet by injecting and forming resin. Hitherto, printing, painting, and the like have often been used in the manufacturing of such decorative sheets. However, in a case where there is a small number of copies, or a short delivery time, manufacturing the decorative sheet using the ink jet recording method is easy. The decorative sheet and formed products using the ink jet recording method are disclosed in JP2009-67860A, for example.

Decorative sheet and in-mold forming method


The present invention concerns a electrical conducting (control) device (5). It is provided that it exhibits at least one conducting-part carrier (5.2) and at least one conducting part (5.1), which is disposed at least partially on and/or for the conducting-part carrier (5.2).

One object of the present invention is an electrical conducting device according to the general terms of claim 1, in particular for heating equipment.
It is well known that graphite particles are used to insert into a synthetic material and to use as a resistance unit. In addition, carbon fibers are known to be used as heat conductors in textile heating elements. Metal wires are also known to be laid on textile surfaces and inserted as heating elements.
Electrical temperature-adjustment devices are being offered which are increasing safety requirements, high cost pressure, and the growing diversification of usages. Hence a need exists for technical solutions that comprehensively fulfill as many of these requirements as possible.


The present invention relates to wavelength tunable DBR semiconductor laser devices in which light waves generated from a plurality of laser portions (or laser channels) are combined. This type of semiconductor laser device requires that the laser channels together cover an entire desired wavelength range, allowing the oscillation wavelength to be continuously varied over this range. However, to accomplish this, it is necessary to employ highly accurate crystal growth and process techniques. Furthermore, the length of the gain region must be reduced to increase the range over which the oscillation wavelength can be continuously varied, making it difficult to achieve laser oscillation.

DBR lasers having a special grating such as an SG (Sampled Grating) or SSG (Super Structure Grating) have been developed for use as wavelength tunable semiconductor lasers to provide any wavelength within the C-band used in wavelength division multiplexer (WDM) systems. In order for these DBR lasers to oscillate at a desired wavelength, it is necessary to control currents to adjust not only the wavelength but also the phase of the light, resulting in a complicated control system. Furthermore, it has been difficult to ensure the long-term reliability of the lasers in terms of wavelength. To overcome the above problems, short cavity DBR lasers have been recently developed which do not require phase control of the light. See, for example, Selected Topics in Quantum Electronics, IEEE Journal, vol. 9, September to October 2003, pp. 1132-1137 (Nonpatent Document 1). However, the wavelength of each channel of these short cavity DBR lasers can be varied only by 10 nm or less. (This range over which the wavelength can be varied is referred to as a "wavelength tunable range".) To increase the wavelength tunable range so as to cover the entire C-band, it is necessary to array a plurality of DBR lasers. In one known semiconductor laser device, for example, the light waves from an array of DBR lasers are combined by a multi-mode interferometer (MMI) and amplified by a semiconductor optical amplifier (SOA).
FIG. 1 shows a laser chip on which a 4 channel DBR laser array, an MMI, and an SOA are monolithically integrated. This example has basically the same geometric configuration as the semiconductor laser devices of the present invention. It should be noted that the wavelength tunable semiconductor lasers of the present invention are different from conventional wavelength tunable semiconductor lasers in dimensional design, as described later in detail. In the laser chip, gain electrodes 101, 102, 103, and 104, DBR electrodes 105, 106, 107, and 108, and an SOA electrode 114 are formed on the surface of an InP substrate 100. It should be noted that in the figure, reference numerals for these electrodes (such as "101") are written beside their electrode pad portions. In the top and cross-sectional views (in FIGS. 2A to 2C described later), the portions of these electrodes directly formed in the waveguide portions, etc. are referred to as "rear DBR electrode 161", "gain electrode 162", "front DBR electrode 163", "SOA electrode 164", etc., respectively. These portions are connected to their respective electrode pads, as shown in the top view. It should be noted that in these figures, the portion of each DBR electrode on the light emitting side (or combiner side) is referred to as the "front DBR electrode", while the portion on the opposite side (or input side) is referred to as the "rear DBR electrode".
The waveguide structure is such that DBR laser channels ch1, ch2, ch3, and ch4 (or 115, 116, 117, and 118) extend in parallel to one another and are connected at the light emitting side to optical waveguides 109, 110, 111, and 112, respectively. The optical waveguides 109 to 112 are connected to an MMI combiner 113 and further connected to the SOA waveguide under the SOA electrode 114. FIG. 2A is a top view of the chip shown in FIG. 1; and FIG. 2B is a cross-sectional view of the chip shown in FIG. 2A taken along line A-B-C-D-E. Specifically, FIG. 2B shows a cross section taken along an optical path that passes through the semiconductor laser portion (from point A to point B) shown in the upper left of the figure, an optical waveguide (B-C), the optical combiner (C-D) for combining a plurality of optical waveguides, and the semiconductor optical amplifier (D-E).
The laser chip has integrated therein a rear DBR region. 138, a gain region 139, a front DBR region 140, an S-shaped waveguide region 141, an MMI region 142, and an SOA region 143. The length of the gain region is reduced to 15 μm to increase the range over which the wavelength can be continuously varied (referred to as the "continuous wavelength tunable range"). Further, front and rear end faces 144 and 145 have a low reflective film coating thereon. The DBR laser portion includes a core layer 132 of the gain region, a refractive index control core layer 134 of the rear DBR region, a refractive index control core layer 135 of the front DBR region, and a grating supply layer 136. The refractive index control core layers 134 and 135 are connected to the core layer 132, and the grating supply layer 136 is formed on the refractive index control core layers 134 and 135. The refractive index control core layer 135 of the front DBR region is also connected to one end of a core layer 137 of the low-loss optical waveguide including the S-shaped waveguide region 141 and the MMI region 142. Further, a core layer 133 of the SOA region is connected to the other end of the core layer 137.
FIG. 3 shows exemplary wavelength characteristics of the laser chip shown in FIG. 1. The four DBR laser channels ch1, ch2, ch3, and ch4 handle different wavelength regions, thereby collectively covering the entire C-band. For example, to generate 1540 nm wavelength light, currents are injected to the gain layer and the SOA layer of the channel ch2 and, at the same time, a current of 50 mA is injected to the DBR layer of the channel ch2. No current is injected to the gain layers and DBR layers of the other DBR laser channels.
[Nonpatent Document]
Selected Topics in Quantum Electronics, IEEE Journal, vol. 9, September to October 2003, pp. 1132-1137.
In order to be able to generate all the wavelengths in a desired range (e.g., the C-band), the above laser chip must be configured such that the channels (ch1 to ch4) are seamlessly connected to one another in terms of wavelength. That is, the DBR current values of these channels at which mode hopping occurs must be appropriately adjusted relative to one another. FIG. 3 above is a diagram showing the relationship between the DBR current and the oscillation wavelength (of each channel). More specifically, the figure shows the wavelength characteristics of the channels ch1, ch2, ch3, and ch4 that cover different wavelength regions. As shown in the figure, there is a jump in the wavelength characteristic curve of each channel (i.e., mode hopping) at approximately 10 mA.
To appropriately adjust the mode-hopping DBR current values of the channels relative to one another, the refractive index of each DBR layer must be set with an accuracy of ±0.002 or better and a distance Lgrt (described below) must set with an accuracy of ±0.02 μm. The distance Lgrt refers to the distance between the center portion of the one of rear grating elements closest to the gain region 139 and the center portion of the one of front grating elements closest to the gain region (wherein the rear grating elements and the front grating elements are formed in the rear DBR region and the front DBR region, respectively, and make up the grating 136). Specifically, the thickness of each DBR layer must be set with an accuracy of ±6 nm and the composition wavelength of each DBR layer must be set with an accuracy of ±10 nm, requiring highly accurate crystal growth and process techniques.
Another problem is that increasing the continuous wavelength tunable range requires the length Lgain of the gain region 139 to be reduced, making it difficult to achieve laser oscillation. FIG. 4 shows calculated values indicating the dependence of the continuous wavelength tunable range Δλcon on the distance Lgrt. It should be noted that in this example, the grating 136 is divided into two grating portions (made up of rear grating elements and front grating elements, respectively) formed within the rear DBR region 138 and the front DBR region 140, respectively, and each grating portion is spaced 5 μm apart from the gain region 139. (These grating portions sandwich the gain region 139.) The distance Lgrt is related to the length Lgain by the following equation.Lgrt=Lgain+10 μm  (1)It should be noted that the above continuous wavelength tunable range curve shown in FIG. 4 was obtained by assuming that the optical coupling coefficient κ of the grating 139 is 90 cm−1. Thus, FIG. 4 shows an exemplary relationship between the distance Lgrt and the range over which the oscillation wavelength can be continuously varied. As be seen from FIG. 4, the distance Lgrt must be set to less than 25 μm (that is, the length Lgain must be set to less than 15 μm) to achieve a continuous wavelength tunable range of more than 10 nm. This requirement is very difficult to meet if laser oscillation is to be produced. Therefore, practically, such a structure is not suitable for mass production.

Wavelength tunable semiconductor laser apparatus

Abstract: Two laser channels operate in combination, and a combiner combines the light waves emitted from these laser portions (or laser channels) so as to cover one entire wavelength range. Specifically, an inter-grating element distance Lgrt1 of the first laser portion is set larger or smaller than an inter-grating element distance Lgrt2 of the second laser portion by one half of the grating pitch. This allows these laser portions to exhibit different mode-hopping DBR current values appropriately adjusted against each other and thereby together cover a desired wavelength range.


A client device may receive encoded video via a transport stream based on a video coding protocol. When errors result in receiving the encoded video, the client device may use an Internet Protocol (IP) connection to recover from the error. For example, an encoder may insert markers inband in the transport stream, and a segmenter then segments the video using the markers. The content remains in the form of a continuous transport stream that is compatible with existing transport stream delivery mechanisms. When an error occurs, the client device can then determine a locator for a segment that can be used to recover from the error and requests the segment from a server through the IP connection. The server sends the segment to the client device at the level of the transport stream layer without adding another protocol layer to encapsulate the segment.

Broadcast or multicast delivery is frequently used to deliver video encoded using a compression standard in a transport stream, such as Motion Picture Experts Group (MPEG) transport streams, to a large number of client devices. Some delivery mechanisms include Internet Protocol television (IPTV) multicast, over-the-air broadcasts (e.g., advanced television systems committee (ATSC)), and direct-to-the-home (DTH) satellite (e.g., digital video broadcasting-satellite (DVB-S)). During the delivery, errors may result in the form of packet loss or corruption. Techniques for providing error resilience or recovery when the errors occur are needed. For example, clients may request a unicast retransmission of portions of the video. To enable this, the video is partitioned and encapsulated in an additional protocol layer, typically real-time transport (RTP). RTP encapsulation adds overhead and is not compatible with the transport stream-based delivery mechanisms used to transport the encoded video, such as the over-the-air broadcasts, satellite delivery, etc., because the RTP transport stream is a higher layer than the MPEG transport stream.

Error recovery for video delivery via a segmentation process


A pop-up sprinkler head is provided with a mechanism that shuts off the water when the nozzle portion of the riser is removed for maintenance. A stopper element reciprocally mounted in the riser moves to a shut off position when the nozzle is removed. A valve seat member and a stopper element may be provided to retrofit the riser of an existing sprinkler head.

This invention relates to irrigation devices and more particularly to pop-up sprinkler heads with means for local water shut off for maintenance. Pop-up sprinklers may require maintenance to unclog an orifice, to clean out a filter or strainer, or to replace an outlet nozzle with one of a different range or to replace one that has been so abraded that its range has become excessive. When the nozzle portion is removed for maintenance, water floods out of the sprinkler head if the water supply to the unit has not been shut off. It is often awkward for the worker to access a shut off valve. After performing necessary maintenance to the head, the water supply must be turned on to see if function is correct. When the head is fed by a sector switching valve, it may be difficult to once again feed the head even if access to the water source is readily available. It would greatly facilitate maintenance of pop-up sprinkler heads if the water supply could be automatically shut off when the nozzle is removed and turned on when the nozzle is replaced.

Pop-up sprinkler head with maintenance features


A method and system for reducing white noise in images. The method does not require knowledge of the image blur or noise statistics, and can remove noise without causing excessive image blur. The image is separated into frequency bands which are then thresholded to remove small image changes, i.e. noise, while maintaining larger changes which are signals. The thresholded components are then recombined to produce an output image with reduced white noise.

1. Field of Invention
This invention is related to noise reduction in video images. More particularly, this invention is directed to a system and method for reducing white noise in images.
2. Description of Related Art
Images, such as still images captured from video signals, can sometimes be quite noisy. This noise generally falls into one of two categories. The first category is xe2x80x9csalt and pepperxe2x80x9d noise. Salt and pepper noise is occasional, high-frequency light or dark pixels caused by electric pulses, such as from nearby engines or motors. The application of a median filter to images containing salt and pepper noise works well to clean up the noisy pixels in the image.
The second category of noise is white, or Gaussian, noise. White noise is a random noise throughout the image and is commonly seen in the xe2x80x9csnowyxe2x80x9d pictures from distant broadcast stations. Approaches to reducing white noise have been either through the application of a Wiener filter, or through averaging over several frames.
While salt and pepper and white noise each have filters that work well to clean-up the pixel errors in images, these filtering approaches may not always be practical. Specifically, the design of an optimal Wiener filter requires knowledge of the communication channel characteristics and of the particular noise statistics. Averaging images, which is a common approach to reducing white noise, requires the availability of several originally identical images. In video signals, this would require that no motion occur in the captured image. Neither of these approaches are possible if only a single image from an unknown source is available.
This invention provides systems and methods for reducing noise in images.
This invention separately provides systems and methods for reducing white noise in still images.
This invention separately provides systems and methods for decomposing a still image into a plurality of frequency bands and recomposing the still image from the filtered frequency bands.
This invention separately provides systems and methods for setting filtering parameters for a frequency band of a still image.
The various systems and methods of this invention reduce white noise by first applying band-pass filters to the image to decompose it into a sequence of frequency bands. A different threshold is then applied to each band. Small changes in the image are considered to be noise and are removed, while large changes are retained as the signal. The various threshold bands are then reassembled to produce the resultant image having reduced white noise content.
These and other features and advantages of this invention are described in or are apparent from the following detailed description of the preferred embodiments.

Method and apparatus for white noise reduction in video images


A medical device provided with at least a partial surface coating of a thermoplastic copolymer of tetrafluoroethylene and perfluoroalkylvinylether that is free of cross-linking monomers and curing agents. The fluoropolymer coating is preferably an amorphous thermoplastic, is highly inert and biocompatible, has elastomeric characteristics that provide desirable mechanical properties such as good flexibility and durability. These characteristics allow the coating to be considered “functionally transparent” because it withstands mechanical deformations required for the assembly, deployment, expansion, and placement of medical devices, without any adverse effect on the mechanical and biological functionality of the coated device. Further, its inertness, derived from the perfluorocarbon structure, contributes to its functionally transparent nature. The coating can be provided with various liquid or solid additives, can be loaded with large quantities of additives including a wide range of therapeutic agents, and has excellent drug elution characteristics when elutable additives are used. The desirable mechanical characteristics are surprising given the absence of cross-linking monomers and curing agents that would otherwise render such materials inadequately biocompatible. The perfluoroalkylvinylether may be perfluoromethylvinylether, perfluoroethylvinylether or perfluoropropylvinylether.

Surgical interventions often involve the implantation of a medical device, typically manufactured from polymeric and/or metallic materials, that is intended to provide a mechanical repair of a medical malady. While providing necessary and often life saving benefits, the implanted metal or polymer material may also produce some type of complication. Some of the more common complications include acute thrombosis; increased risk of infection immediately post procedure and/or chronically; fibrous encapsulation of the device resulting from a foreign body response and inflammation; and vascular proliferative disease resulting in an excessive, inflammatory, fibroproliferative response to injury.
In some cases therapeutic agents are administered to ameliorate complications arising from the medical implant and the disease being treated. Most often these are administered orally or through injection and result in systemic delivery. Ideally therapeutic agents would be released locally in a controlled fashion from an implant to maximize the effectiveness of the agent at the desired site without causing severe systemic side effects. A combination device, or product, that provides for local drug delivery and a mechanical solution to the medical malady may result in clinical outcomes not possible otherwise. One approach to achieving this combination is through the use of coatings applied to the surfaces of medical devices, implantable for short or long terms, wherein the coating may optionally contain therapeutic agents elutable from the coating.
Many systemic pharmacological approaches to reducing restenosis have been proposed including the use of various agents such as anticoagulants, antiplatelet agents, metalloprotease inhibitors, antiproliferative agents and anti-inflammatory agents. Many of these compounds have demonstrated some level of positive effect in animal models of restenosis. Unfortunately, the clinical application of these compounds has shown no positive indications. This ineffectiveness may be largely attributed to the inability of systemic delivery to provide effective drug concentrations at the desired site. The dose and manner in which these compounds are administered is suboptimal, necessitating the development of new delivery modalities, technologies, and materials to accomplish effective localized delivery. Furthermore, potentially useful but toxic agents that would otherwise not be considered because of problematic systemic concentration from injections or oral dosage forms, could be used in combination products with an effective localized delivery system.
While there is large potential for combination products that provide therapeutic delivery with medical devices, development has been slow. For example, the use of localized stent-based drug delivery to reduce restenosis has only recently been demonstrated in limited clinical trials. Many of the drugs being proposed for use in these combination devices have existed for many years. Paclitaxol is a prime example as it has long been used as a cancer therapy, and its effects on vascular cells have been known for some years. The slow emergence of these combination products then appears to be due to the lack of adequate materials to combine the drug and device into one medical embodiment that meets all the needs for clinical applications. Each combination product requires a suitable drug, a robust medical device, and a means to combine these two elements together in a single entity. Most often a polymer coating has been proposed as the material to combine the drug and device into a single entity. Unfortunately, many of the materials currently available have numerous shortcomings.
There is a need for biocompatible materials that can adequately retain an efficacious dose, provide for prolonged drug release, and be incorporated into the mechanical device, in the simplest possible fashion, without compromising the device functionality. Moreover, the material would truly be exemplary if it provided more benefits to the combination product than functioning solely as a matrix for the release of a therapeutic agent. Preferably, this can be accomplished without the addition of still another component, such as an adhesive material or primer coatings, or without requiring surface modification of the medical device, but rather with the polymer material itself serving as a biocompatible adhesive with or without additives.
The utilization of biodegradable materials for drug delivery such as alpha hydroxy esters is well known. These compounds have glassy or rigid amorphous states that do not meet the flexibility requirements of combination implantable device. These materials have poor adhesive properties, particularly with regard to common materials used to manufacture medical devices such as various metals and polymers such as polytetrafluoroethylene (PTFE). The biodegradable nature of these materials requires judicious use so as not to create fragmentation of the material and possibly the device as they degrade.
Silicones are among the most widely used synthetic polymers that are intended to be non-biodegradable and are found in a variety of medical applications. They are sometimes used as a matrix material for elution of therapeutic agents, and as an elastomer they offer a good degree of flexibility. See, for example, U.S. Pat. No. 6,358,556 to Ding et al. Silicones consist of at least three components: an elastomer, silica reinforcing agent, and a volatile inhibitor to stop cross-linking. However, silicones have poor bonding strengths to many medical device substrate materials, and poor long-term in vivo tensile strength. They are less biocompatible than most fluoropolymers. Silicones absorb lipids and proteins over time, have a tendency to generate particulate debris over time, and exhibit poor abrasion resistance. Curatives in the vulcanized polymer can be problematic in that they may react with additive. Other problems are known to include cracking, swelling (generally due to lipid or protein absorption), tear propagation and poor adhesion. These problems are exacerbated by the use of additives.
Various fluoropolymer materials have been proposed as drug delivery material; see, for example, EP 950386 to Llanos et al. which suggests a list of materials including PTFE. While PTFE is particularly inert and highly biocompatible, it is not elastomeric and is limited in elution capability if not used in its porous expanded form (ePTFE). Drugs are typically eluted from the interconnected void spaces of ePTFE rather than by molecular diffusion from within the polymer matrix; see, for example, U.S. Pat. No. 5,290,271 to Jemberg. EP 1192957 to Llanos et al., proposes other fluoropolymer materials comprising a first monomer chosen from the group consisting of vinylidene fluoride and a second monomer that is different from the first monomer. These materials are relatively non-durable according to examples that describe cracking of the matrix during device expansion. Likewise, these particular materials are limited in their drug loading and drug elution capabilities. The ability to bond to a variety of other materials without requisite primer coating or surface treatment of the substrate, the ability to function as an integral component of a coated medical device (without adverse effect on the device function), and the ability to aid in the manufacturing of a wide range of combination products has not been shown

Thermoplastic fluoropolymer-coated medical devices


A system and method for determining a user affinity for a category. The system calculates an affinity score based on a record of actions performed on the document by a user and a categorization of the document. This affinity score is computed by a weighted sum of factors associated with the document. The affinity score is normalized and a population threshold is applied. A predetermined percentage of the population of users associated with the document is determined and those users are said to have an affinity for at least one category assigned to the document. The system may also decay an affinity score if a user has not performed at least one action on the document. If the user performs an action on the document, however, the affinity may be reset. A user, system administrator or other user may also be enabled to decline an affinity for a category.

Many organizations have some form of employee directory and usually have made an attempt to augment this directory with personal profile attributes such as memberships, position, title or project affiliations. Many have attempted to expand each employee's profile by adding skills inventory, educational background or professional accomplishments. Many of these efforts have been successful, but most have not fulfilled their goal. The effort required to update and maintain such a profile and a subjective nature of self-description leads to inaccuracies or stale data.
Often, people who have relevant knowledge in a particular topic are not contacted because a method to search for persons with such knowledge has not been implemented. Most such people finder systems fail due to a lack of timely updates to an employee's profile. In addition, knowledgeable workers may not consider their experience to be valuable to others and may overlook this when manually completing profile forms. The result is that many manually built expertise locator systems are irrelevant or become outdated and eventually fail.
These and other drawbacks exist.

System and method for calculating a user affinity

International Business Machines Corporation


A liquid crystal display (LCD) and corresponding driving method. The LCD includes a liquid crystal display panel for displaying images, a gate driver and a source driver for supplying scan signals and analog pixel signals to gate and data lines of the liquid crystal panel, a backlight unit having a side radiation type LED array that is driven sectionally by a plurality of unit areas to irradiate light to the liquid crystal display panel, and a luminance controller for controlling a luminance of the LED array by unit areas according to surrounding units areas.

1. Field of the Invention
The present invention relates to a liquid crystal display (LCD) and its driving method, and more particularly to an LCD that comprises a side radiation type light emitting diode (LED) and corresponding driving method.
2. Description of the Related Art
An LCD is a display apparatus including a liquid crystal material with an anisotropic dielectric constant injected between upper and lower transparent insulation substrates. Further, a common electrode, a color filter and a black matrix are formed on the upper substrate, and a switching element and a pixel electrode are formed on the lower substrate. In addition, a strength of an electric field formed in the liquid crystal material is controlled by applying a different potential to the pixel electrode and the common electrode to change an alignment of molecules of the liquid crystal material to thus control an amount of light transmitted through the transparent insulation substrates, thereby displaying desired images. In addition, a thin film transistor (TFT) LCD using TFTs as switching elements is commonly used.
Further, because the LCD is a light receiving type display apparatus that does not emit light by itself, a back light unit (BLU) for uniformly sustaining a brightness of an overall screen is installed at a rear surface of the LCD panel. A BLU includes a light emitting diode array and has either a top radiation type LED or a side radiation type LED.
In addition, the BLU using the side radiation type LED has an advantage in terms of panel uniformity and color mixing of the liquid crystal display panel. However, the side radiation type LED has a problem because the light is spread to cover a large area, and thus it is not suitable to be used for sectional driving (division driving) for which light irradiation is controlled at each unit area (UA) of the LCD panel.

Liquid crystal display and method for driving the same


This invention relates to aqueous compositions for hair treatment, comprising polyorganosiloxanes A) having di- and trihydroxy-substituted aromatic groups and at least one surfactant B) selected from cationic surfactants B1) and anionic surfactants B2) in a certain weight ratio of the surfactant B) to the polyorganosiloxane A), and said aqueous compositions having a certain pH. The invention further relates to hair treatment compositions, comprising said aqueous compositions and to hair treatment processes using said aqueous compositions or hair treatment compositions.

Hair generally can be straight, wavy, curly, kinky or twisted. A human hair includes three main morphological components, the cuticle (a thin, outer-most shell of several concentric layers), the cortex (the main body of the hair), and, in case of higher diameter hair, the medulla (a thin, central core). The cuticle and cortex provide the hair strand's mechanical properties, that is, its tendency to have a wave, curl, or kink. A straight hair strand can resemble a rod with a circular cross-section, a wavy hair strand can appear compressed into an oval cross-section, a curly strand can appear further compressed into an elongated ellipse cross-section, and a kinky hair strand cross-section can be flatter still.
The primary component of hair is the cross-linked, alpha-helix protein keratin. Keratins are intermediate filament proteins found specifically in epithelial cells, e.g. human skin and hair, wool, feathers, and nails. The α-helical type I and II keratin intermediate filament proteins (KIFs) with molecular weights around 45-60 kDa are embedded in an amorphous matrix of keratin-associated proteins (KAPs) with molecular weights between 20 to 30 kDa (M. A. Rogers, L. Langbein, S. Praetzel-Wunder, H. Winter, J. Schweizer, J. Int Rev Cytol. 2006; 251:209-6); both intra- and intermolecular disulfide bonds provided by cystines contribute to the cytoskeletal protein network maintaining the cellular scaffolding. In addition to the disulfide cross-links ionic bonding or salt bridges which pair various amino acids found in the hair proteins contribute to the hair strand's outward shape.
It is known in the art that hair can be treated with functionalized silicones which deliver one or more cosmetic benefits, such as conditioning, shine and UV protection as well as color retention. Typically, these silicones are physically deposited on the fiber surface (cuticle) and therefore responsible for the outward appearance of the hair. They can be removed partially or completely by repeated washing processes. While the deposited silicones considerably improve the surface properties of hair, i.e. smoothness and friction, they do not substantially impact the shape, the mechanical properties and the release properties of the hair. Alternative hair treatment methods are available, but these often involve the use of harsh and regulated substances. There has been a need for efficient compounds for the treatment of hair which can be synthesized in a straight forward and cost efficient way, which are easy to formulate and easy to use, yielding long term stable formulations even in the presence of other performance ingredients and which are useful for strengthening of hair, for hair color retention, for hair color enhancement, for hair color protection, for shaping of hair, i.e. the curling and straightening of hair, for hair conditioning, for hair smoothening or softening, for hair straightening, and for improving manageability of the hair, in particular for improving the combability of the hair. In particular, benefits regarding the retention of artificial hair colours without the usage of strongly irritating auxiliaries should be achieved.
WO2016046178 discloses polyhydroxyaromatic silicones for the treatment of hair. It does not disclose long term stable aqueous compositions that are easy to prepare and easy to use and where the polyhydroxyaromatic polyorganosiloxanes are stably dissolved even in the presence of other performance ingredients. Only this type of formulation guarantees a straight transport into the hair and a high crosslinking power.
Accordingly there was a need for long term stable, easy to prepare and easy to use compositions which are in addition robust towards the presence of other performance ingredients and which provide a hair strengthening benefit and a hair coloration benefit accompanied by a benefit on a silicone typical hair smoothness without the usage of strongly irritating auxiliaries.
The present inventors found that aqueous compositions for hair treatment, comprising polyorganosiloxanes A) having di- and trihydroxy-substituted aromatic groups and at least one surfactant B) selected from cationic surfactants B1) and anionic surfactants B2) in a certain weight ratio of the surfactant B) to the polyorganosiloxane A), and said aqueous compositions having a certain pH can be synthesized in a straightforward and cost-efficient way, are easy to formulate and to use, have long-term stability, and are useful for strengthening of hair, for hair coloring, for hair color retention, for hair color enhancement, for hair color protection, for shaping of hair, i.e. the curling and straightening of hair, for hair conditioning, for hair smoothening or softening, for hair straightening, and for improving manageability of the hair, in particular for improving the combability of the hair.

Aqueous compositions for hair treatment comprising polyorganosiloxanes with polyhydroxyaromatic moieties


A process for preparing a pigmented polyimide article having a polyimide matrix with finely divided pigment particles uniformly dispersed therein. The process includes the steps of milling pigment particles in an organic solvent, pre-wetting the pigment particles with a thermoplastic polyamic acid precursor derived from 4,4'-oxydiphthalic dianhydride and an aromatic and/or aliphatic diamine, admixing the treated pigment particles with a polyamic acid polymerization mixture to form a dope, shaping the dope and thermally or chemically converting the shaped dope into a polyimide article containing the pigment particles uniformly dispersed therein.

This invention relates to a process for preparing a polyimide shaped article, e.g. a sheet or film, containing pigment particles, such as carbon or alumina, and having improved tensile and dielectric strength, elongation and electrical conductivity.
Pigment containing polyimide articles, such as polyimide film, are well-know in the art and are generally prepared by blending pigment particles into the polyamic acid precursor and then shaping and curing the polyamic acid to form the polyimide.
For example, Canadian Patent 708,896 discloses an electrically conductive polyimide composition prepared by blending conductive carbon particles, e.g. carbon blacks, in the precursor polyamic acid; shaping the particle containing polyamic acid into a structure; and then thermally converting the shaped structure into a polyimide containing the carbon particles.
U.S. Pat. No. 5,078,936, issued to Parish et al on Jan. 7, 1992, discloses an electrically conductive polyimide article prepared by blending carbon black and graphite in a polar solvent to form a slurry, mixing the slurry with a polyamic acid precursor to form a dope, shaping the dope into a structure and then converting the shaped structure into the polyimide article.
Normally, the blending of the pigment particles is performed while the polyamic acid is in solution in an organic solvent, such as N,N-dimethylacetamide. In order to facilitate particle dispersion and maximize wetting of the pigment particles with the polyamic acid polymer, the pigment particles are slurried in the polymer solvent in a ball, sand or Kady mill. Typically, the pigment particles have a higher density than the solvent and tend to settle and reagglomerate. In addition, the level of adhesion between the polyamic acid polymer and the pigment particles is oftentimes very low and results in lowering of the properties of the polyimide film, e.g. decreased dielectric strength, tenacity and elongation.
It has now been found that shaped polyimide articles containing pigment particles can be prepared by first pre-wetting the pigment particles in an organic solvent with a thermoplastic polyamic acid precursor derived from 4,4'-oxydiphthalic dianhydride and an aliphatic and/or aromatic diamine; admixing the precursor treated pigment particles with a polymerization mixture of an aromatic tetracarboxylic acid dianhydride and an aromatic diamine in the organic solvent and thermally or chemically converting the polyamic acid containing the pigment particles to the polyimide. Polyimide articles containing alumina prepared according to the process of the invention have improved tensile strength, elongation and dielectric strength, and polyimide articles containing carbon have improved electrical conductivity. Polyimide articles of this invention are suitable for use in electronics, copier belt, heating tape, opaque film and thermally conductive film applications.

Process for preparing a pigmented polyimide shaped article


The new and distinct cultivar of perennial Salvia plant named ‘Back to the Fuchsia’ characterized by its medium-sized, dark-pink flowers from deep purplish-red buds densely arranged in verticils and dark greyish-red calyxes and stems with intense light. The new plant has a medium height, compact, rounded habit with stiff, upright, heavily-branched stems and a strong vigorous growth rate and gray-green foliage. ‘Back to the Fuchsia’ is useful for landscaping as a specimen plant or en masse.

The present invention relates to a new and distinct cultivar of perennial Salvia plant hereinafter referred to by the cultivar name Salvia 'Back to the Fuchsia' or as the new plant. The new plant was selected from a block of seedlings resulting from an insect pollination in late spring of 2014 with the unreleased, proprietary hybrid known as "13-24-1 x OP" as the female or seed parent and the male or pollen parent is unidentified sibling of "13-24-1 x OP" in an isolation block at a wholesale perennial nursery in Zeeland, Mich., USA. Seed was collected on Jun. 11, 2014 and sown at the same nursery. The new plant was initially evaluated in the summer of 2016 and assigned the breeder code 14-10-2 through the trial process prior to assigning a cultivar name.
The new Salvia was further evaluated and asexually propagated initially by division and later by basal cuttings taken at the same nursery in Zeeland, Mich., USA in 2016. Evaluation of these and further cutting grown plants shows that Salvia 'Back to the Fuchsia' continues to be stable and produce true to type plants in successive generations of asexual propagation.


An improved structure of a feeder for supplying water and pet food is disclosed. Therein, a base has a shifting space adjacent to a side of a bowl settled in the base so as to receive a dispensing controller. A container unit equipped with a hopper and a water supplier is provided on top of the dispending controller. The dispensing controller can be shifted in the shifting space so that an opening limit is formed when projections formed on two rear ends of the dispensing controller abut against blocks provided bilaterally in the shifting space, and a closing limit is formed when a groove of the dispensing controller abuts against a stop plate formed at a rear section of the shifting space. Thus, the container unit can be easily opened to dispense pet food or closed to not dispense pet food.

1. Technical Field
The present invention relates to an improved structure of a feeder for supplying water and pet food. More particularly, the present invention relates to a control design of a feeder containing pet food (for dogs, cats and the like) so that the feeder, when used outdoors, can be easily operated to dispense or not dispense the pet food.
2. Description of Related Art
Devices for timely supplying food and water to pets (such as cats, dogs and the like) in an outdoor setting have various configurations. For example, an improved structure of a feeder for supplying water and pet food was proposed by the inventor of the present invention previously, wherein pet food is poured into the feeder through a hopper and stored in a container unit. The level of pet food in a transparent inner tube can be observed through a through slot on an outer tube. When feeding is not necessary, the outer tube can be rotated so that a knob connected to a lower end of the outer tube is simultaneously rotated. As a result, a dispensing outlet on the knob is closed to a connecting portion of a base. When feeding is desired, the outer tube can be rotated so that the dispensing outlet on the knob corresponds to the connecting portion of the base, thereby allowing the pet food to fall smoothly into a bowl settled in the base and be eaten by pets.

Structure of feeder for supplying water and pet food


A sliding rack apparatus having a rack body having supported on a slide rest and movable along a pair of slide tracks. The slide rest has a pair of rollers with a rut therebetween. The slide tracks have a convex edge in a center thereof so as to extend in the rut between the rollers. A braking device has a T-shaped plate with a rim that is pivotable between a first portion engaging the convex edge and a second position free of the convex edge.

Generally, a rack is to be fixed at a certain place to hold and store articles. However, in some special locations, such as supermarkets and storehouses, the size and number of racks are too big and any relocation and sorting of articles require large amount of time and labor, resulting in waste of time and labor force as well as increasing cost. Consequently, this kind of fixed rack is not desirable.
Therefore, an ideal and practical rack is called for to solve the above problems.
In light of this, this invention intends to propose a new rack structure.


A posture estimation device that is capable of highly precisely estimating the posture of an object comprising multiple parts. Said device (100) comprises: a posture information database (110) that for each of multiple postures, holds posture information that defines the placement of multiple parts; a fitting unit (160) that computes, for each of the parts in an image, a correlation level between the placement of the parts and the posture information; a difficulty level information table (130) that holds an estimation difficulty level that is a degree of difficulty of estimating each part position and computed on the basis of each parallel line components of each of the parts contained in the posture information; and a posture estimation unit (170) that to the correlation level, applies a weighting based on the estimation difficulty level, and on the basis of the weighted correlation level, estimates the posture of the object.

Estimation of the posture of a person based on image data from a captured moving image has been an active area of research in recent years. Estimating behavior using time series information of an estimated posture allows a posture estimation apparatus to determine the behavior of the person by computer analysis based on moving images, and can thus perform behavior analysis that does not depend on human effort. Examples of behavior analysis include detection of unexpected behavior on streets, analysis of purchasing behavior in stores, support for the enhancement of work efficiency in factories, and form coaching in sports.
It is desirable that this kind of posture estimation is performed without attaching an apparatus such as a direction sensor to a person. The reason is that if posture estimation is performed by attaching an apparatus to a person, it is difficult for a random person to be taken as an estimation target, and the cost will increase if there are a large number of estimation targets.
Therefore, as posture estimation that takes a random person as a target, as disclosed, for example, in PTL 1, technology has been proposed that estimates the orientation of the body of a person on the basis of a video obtained by photographing the person.
The technology disclosed in PTL 1 (hereunder, referred to as "related art") estimates candidates for a posture that can be assumed next (hereunder, referred to as "next candidate posture") based on the posture that was estimated the previous time (hereunder, referred to as "previous estimation posture"). The related art compares the position of each part of the next candidate posture with an image of the part in a photographed image, and retrieves a candidate posture with the highest correlation.
However, depending on the posture, a certain part of a person is hidden by another part, and a portion or all of the certain part cannot be recognized on an image (hereunder, such a state is referred to as "concealed"). According to the related art, if there is a part that is being concealed (hereunder, referred to as "concealed part") in this manner, in some cases the outlines of different postures may resemble each other, which makes it impossible to perform correct posture estimation in some cases.
Therefore, according to the related art, an area (number of pixels) that each part occupies in an image is determined with respect to the previous estimation posture, and a part whose area is less than or equal to a threshold is extracted as a concealed part. Further, according to the related art, if there is a concealed part in the previous estimation posture, the degree of freedom with respect to the posture of the concealed part is set higher than that of a part that is not concealed, and the degree of freedom with respect to the next candidate postures is expanded to increase the number of candidate postures. Therefore, according to the related art, even in a case where the previous estimation posture was erroneous due to the difficulty of estimating the position of a concealed part (the lowness of the estimation accuracy), posture estimation can be performed that takes into account a fact that the next candidate postures include a correct posture.

Posture estimation device and posture estimation method