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1. A method for modulating the activity of a cardiac ryanodine receptor calcium channel comprising contacting a cardiac ryanodine channel with an amount of a fragment of a skeletal dihydropyridine receptor polypeptide or derivative, homologue or analogue sufficient to modulate the activity of said ryanodine channel. 2. The method according to claim 1 wherein said method comprises the additional step of determining the activity of said cardiac ryanodine calcium channel. 3. The method according to claim 1 or 2 wherein said modulation is upregulation. 4. The method according to claim 3 wherein said fragment is applied at a concentration in the range of about 1 nm to about 10 μM. 5. The method according to claim 1 or 2 wherein said modulation is down-regulation. 6. The method according to claim 5 wherein said fragment is applied at a concentration in excess of about 10 μM. 7. The method according to any one of claims 1-6 wherein said fragment comprises at least five contiguous amino acid residues of the peptide sequence: Thr Ser Ala Gin Lys Xaa Xaa Xaa Xaa Glu Glu Xaa Xaa Arg Ser Lys Xaa Xaa Xaa Xaa Xaa (SEQ ID NO:1) and the RKRRK motif. 8. The method according to claim 7 wherein said peptide sequence corresponds to any one of the following peptide sequences: (i) Thr Ser Ala Gln Lys Ala Lys Ala Glu Glu Arg Lys Arg Arg Lys Met Ser (SEQ ID NO: 3) Lys Gly Leu (ii) Thr Ser Ala Gln Lys Ala Lys Ala Glu Glu Arg Lys Arg Arg Lys Met Ser (SEQ ID NO: 4) Arg Gly Leu (iii) Thr Ser Ala Gln Lys Ala Lys Ala Glu Glu Arg Lys Arg Arg Lys Met Ser (SEQ ID NO: 2) Arg Gly Leu (iv) Thr Ser Ala Gln Lys Ala Lys Ala Glu Glu Arg Lys Arg Arg Lys Met Ala (SEQ ID NO: 8) Arg Gly Leu (v) Thr Ser Ala Gln Lys Ala Lys Ala Glu Glu Arg Lys Arg Arg Lys Met Ser (SEQ ID NO: 9) Xaa Gly Leu (vi) Thr Ser Ala Gln Lys Ala Lys Ala Glu Glu Arg Lys Arg Arg Lys Met Ala (SEQ ID NO: 10) Xaa Gly Leu or a functional derivative, homologue or amologue thereof. 9. The method according to claim 1-8, wherein said peptide sequence comprises at least 10 contiguous amino acid residues and more preferably at least 15-20 contiguous amino acid residues. 10. The method according to claim 9 wherein said fragment is a basic charged fragment. 11. A method for identifying a peptide or non-peptide modulator of a cardiac ryanodine calcium channel comprising: (i) incubating an amount of a fragment of a skeletaldihydropyridine receptor polypeptide or a homologue, analogue or derivative thereof that modulates cardiac ryanodine channel activity in the presence of a functional cardiac ryanodine calcium channel under conditions appropriate for calcium channel activity to be modulated and determining the activity of the channel; (ii) incubating a candidate peptide or non-peptide compound in the presence of said functional cardiac ryanodine calcium channel under conditions appropriate for calcium channel activity to be modulated by said dihydropyridine receptor polypeptide fragment or a homologue, analogue or derivative thereof and determining the activity of the channel; and (iii) comparing the activity at (i) and (ii). 12. The method according to claim 11 wherein said modulation is up-regulation. 13. The method according to claim 12 wherein said fragment is applied at a concentration in the range of about 1 nm to about 10 μm. 14 The method according to claim 13, wherein said modulation is down-regulation. 15. The method according to claim 14, wherein said fragment is applied at a concentration in excess of about 10 μM. 16. The method according to any one of claims 11-15 wherein said fragment comprises the peptide sequence: Thr Ser Ala Gln Lys Xaa Xaa Xaa Xaa Glu Glu Xaa Xaa Arg Ser Lys (SEQ ID NO: 1) Xaa Xaa Xaa Xaa Xaa and the RKRRK motif. 17. The method according to any one of claims 11 to 16, wherein said peptide sequence corresponds to any one of the following peptide sequences: (i) Thr Ser Ala Gln Lys Ala Lys Ala Glu Glu Arg Lys Arg Arg Lys Met Ser (SEQ ID NO: 3) Lys Gly Leu (ii) Thr Ser Ala Gln Lys Ala Lys Ala Glu Glu Arg Lys Arg Arg Lys Met Ser (SEQ ID NO: 4) Arg Gly Leu (iii) Thr Ser Ala Gln Lys Ala Lys Ala Glu Glu Arg Lys Arg Arg Lys Met Ser (SEQ ID NO: 2) Arg Gly Leu (iv) Thr Ser Ala Gln Lys Ala Lys Ala Glu Glu Arg Lys Arg Arg Lys Met Ala (SEQ ID NO: 8) Arg Gly Leu (v) Thr Ser Ala Gln Lys Ala Lys Ala Glu Glu Arg Lys Arg Arg Lys Met Ser (SEQ ID NO: 9) Xaa Gly Leu (vi) Thr Ser Ala Gln Lys Ala Lys Ala Glu Glu Arg Lys Arg Arg Lys Met Ala (SEQ ID NO: 10) Xaa Gly Leu or a functional derivative, homologie or amalogue thereof. 18. The method according to any one of calims 11-17, wherein said peptide comprises at least 10 contiguous amino acid residues and more preferably at least 15-20 contiguous amino acid residues. 19. The method according to claim 18, wherein said fragment is a basic charged fragment. 20. A process comprising: (i) identifying candidate agonists and antagonists of a cardiac ryanodine calcium channel; (ii) determining those compounds at (i) that actually activate or inhibit the activity of a cardiac ryanodine channel; (iii) determining which compounds at (ii) have higher binding affinities for said cardiac ryanodine calcium channel than any one of SEQ ID NOs: 1-10; and (iv) optionally, determining the sites of interaction between those compounds at (iii) and said cardiac ryanodine calcium channel. 21. A method of determining whether a cardiac ryanodine channel is open or has a high channel open probability said method comprising contacting a cardiac ryanodine channel with an amount of a fragment of a skeletal dihydropyridine receptor polypeptide for a time and under conditions sufficient for binding to ryanodine to occur and determining the binding of said peptide to ryanodine, wherein binding of said peptide to ryanodine indicates a high channel open probability and wherein non-specific peptide binding of peptide to the channel pore indicates a low channel open probability. 22. The method according to claim 25 wherein said fragment comprises at least 5 contiguous amino acid residues of the peptide sequence: Thr Ser Ala Gin Lys Xaa Xaa Xaa Xaa Glu Glu Xaa Xaa Arg Ser Lys Xaa Xaa Xaa Xaa Xaa (SEQ ID NO:1) and the RKRRK motif. 23. The method according to claim 22, wherein said peptide sequence corresponds to any one of the following peptide sequence: (i) Thr Ser Ala Gln Lys Ala Lys Ala Glu Glu Arg Lys Arg Arg Lys Met Ser (SEQ ID NO: 3) Lys Gly Leu (ii) Thr Ser Ala Gln Lys Ala Lys Ala Glu Glu Arg Lys Arg Arg Lys Met Ser (SEQ ID NO: 4) Arg Gly Leu (iii) Thr Ser Ala Gln Lys Ala Lys Ala Glu Glu Arg Lys Arg Arg Lys Met Ser (SEQ ID NO: 2) Arg Gly Leu (iv) Thr Ser Ala Gln Lys Ala Lys Ala Glu Glu Arg Lys Arg Arg Lys Met Ala (SEQ ID NO: 8) Arg Gly Leu (v) Thr Ser Ala Gln Lys Ala Lys Ala Glu Glu Arg Lys Arg Arg Lys Met Ser (SEQ ID NO: 9) Xaa Gly Leu (vi) Thr Ser Ala Gln Lys Ala Lys Ala Glu Glu Arg Lys Arg Arg Lys Met Ala (SEQ ID NO: 10) Xaa Gly Leu or a functional derivative, homologue or amalogue thereof. 24. The method according to any one of claims 21-23 wherein said peptide comprises at least 10 contiguous amino acid residues and more preferably at least 15-20 contiguous amino acid residues. 25. The method according to claim 24 wherein said fragment is a basic charged fragment. 26. A method of treatment of cardiac dysfunction in a human or animal subject comprising administering an effective amount of a fragment of a skeletal dihydropyridine receptor polypeptide comprising a RKRRK motif for a time and under conditions sufficient for enhanced cardiac contraction to occur thereby rectifying said cardiac dysfunction. 27. The method according to claim 30 wherein said cardiac dysfunction is myocardial contractile failure, ischemic heart disease, systemic inflammatory states such as sepsis, cardiac hypertrophy (calcium overload), cardiomyopathy such as arrhythmogenic right ventricular dysplasia type-2 (ARVD2), and drug (e.g. cocaine)-induced cardiomyopathy, infarction, dysrhythmia, congestive heart failure, or heart attack. 28. The method according to claim 32 or 33 wherein said fragment comprises at least 5 contiguous amino acid residues of the peptide sequence: Thr Ser Ala Gln Lys Xaa Xaa Xaa Xaa Glu Glu Xaa Xaa Arg Ser Lys (SEQ ID NO: 1) Xaa Xaa Xaa Xaa Xaa and the RKRRK motif. 29. The method according to claim 34 wherein said peptide sequence corresponds to any one of the following peptide sequences: (i) Thr Ser Ala Gln Lys Ala Lys Ala Glu Glu Arg Lys Arg Arg Lys Met Ser (SEQ ID NO: 3) Lys Gly Leu (ii) Thr Ser Ala Gln Lys Ala Lys Ala Glu Glu Arg Lys Arg Arg Lys Met Ser (SEQ ID NO: 4) Arg Gly Leu (iii) Thr Ser Ala Gln Lys Ala Lys Ala Glu Glu Arg Lys Arg Arg Lys Met Ser (SEQ ID NO: 2) Arg Gly Leu (iv) Thr Ser Ala Gln Lys Ala Lys Ala Glu Glu Arg Lys Arg Arg Lys Met Ala (SEQ ID NO: 8) Arg Gly Leu (v) Thr Ser Ala Gln Lys Ala Lys Ala Glu Glu Arg Lys Arg Arg Lys Met Ser (SEQ ID NO: 9) Xaa Gly Leu (vi) Thr Ser Ala Gln Lys Ala Lys Ala Glu Glu Arg Lys Arg Arg Lys Met Ala (SEQ ID NO: 10) Xaa Gly Leu or a functional derivative, homologue or amalogue thereof. 30. The method according to any one of claims 26-29 wherein said peptide comprises at least 10 contiguous amino acid residues and more preferably at least 15-20 contiguous amino acid residues. 31. The method according to claim 38 wherein said fragment is a basic charged fragment. 32. The use of a fragment of a skeletal dihydropyridine receptor peptide comprising at least 5 contiguous amino acid residues of the peptide set forth in any one of SEQ ID NOs: 1-10 and the RKRRK motif or a functional homologue, analogue, or derivative thereof, to modify the activity of cardiac ryanodine calcium channel, thereby modifying defective calcium signaling. 33. Use according to claim 32 wherein said peptide comprises at least 10 contiguous amino acid residues and more preferably at least 15-20 contiguous amino acid residues. 34. Use according to claim 32 or 33 wherein said defective calcium signaling induces chronic hypertrophy, dilated cardiac myopathy or heart failure. 35. Use according to claim 32 or 33 wherein said peptide or homologue, analogue or derivative thereof is administered as a dosage that can enhance contractile force, and further increase intracellular calcium concentration (i.e. [Ca2+]i) during systole, and further decrease [Ca2+]i during diastole. 36. Use according to claim 35 wherein said peptide or a homologue, analogue or derivative thereof induces at least about a 3% or 5% increase in systolic [Ca2+]i relative to the systolic [Ca2+]i. 37. Use according to claim 35 wherein said peptide or a homologue, analogue or derivative thereof induces at least about a 3% or 5% decrease in diastolic [Ca2+]i relative to the diastolic [Ca2+]i. 38. Use according to either claim 36 or 37 wherein said systolic [Ca2+]i is increased, or diastolic [Ca2+]i is decreased, by at least about 10% or 15%, and still more preferably by at least about 20%, 25%, 30%, 40% or 50%, relative to the systolic [Ca2+]i or diastolic [Ca2+]i respectively. 39. Use according to any one of claims 32-38 wherein said administered peptide induces an improvement in the efficiency of cardiac contraction. 40. Use according to claim 39 wherein said cardiac contraction is enhanced by inducing at least about a 5% or 10% increase in preload-recruitable stroke work at within 0.5-1.0 hr following administration. 41. Use according to claim 40 wherein said cardiac contraction is enhanced by about 15%, 20%, 30%, 40%, 50%, 55%, 60% or 70%. 42. The use of a fragment of a skeletal dihydropyridine receptor polypeptide comprising at least 5 contiguous amino acid residues of the peptide set forth in any one of SEQ ID NOs: 1-10 and a RKRRK motif or a homologue, analogue or derivative thereof in the manufacture of a medicament for the treatment of cardiac dysfunction in a human or animal subject. 43. Use according to claim 41 wherein said cardiac dysfunction is myocardial contractile failure, ischemic heart disease, systemic inflammatory states such as sepsis, cardiac hypertrophy (calcium overload), cardiomyopathy such as arrhythmogenic right ventricular dysplasia type-2 (ARVD2), and drug (e.g. cocaine)-induced cardiomyopathy, infarction, dysrhythmia, congestive heart failure, or heart attack. 44. Use according to claim 50 or 51 wherein said peptide comprises at least 10 contiguous amino acid residues and more preferably at least 15-20 contiguous amino acid residues. 45. A pharmaceutical composition comprising a fragment of a skeletal dihydropyridine receptor polypeptide, which peptide comprises at least about 5 contiguous amino acid residues of the peptide set forth in any one of SEQ ID NOs: 1-10 amd a RKRRK motif or a functional homologue, analogue or derivative thereof together with one or more pharmaceutically acceptable carriers and/or diluents. 46. The pharmaceutical composition according to claim 45 wherein said peptide comprises at least 10 contiguous amino acid residues and more preferably at least 15-20 contiguous amino acid residues. 47. The pharmaceutical composition of claim 45 or 46 when used according to the method of any one of claims 25-30. |
<SOH> BACKGROUND TO THE INVENTION <EOH>Bibliographic details of the publications referred to in this specification are collected at the end of the description. Reference herein to prior art, including any one or more prior art documents, is not to be taken as an acknowledgment, or suggestion, that said prior art is common general knowledge in Australia or forms a part of the common general knowledge in Australia. Excitation-contraction coupling is essential to the functioning of striated muscles, such as cardiac and skeletal muscles, linking electrical excitation to mechanical activity. Key components of excitation-contraction coupling are the dihydropyridine receptor (DHPR), a voltage-dependent Ca 2+ channel of the transverse tubule (TT), and the Ca 2+ release channel or ryanodine receptor (RyR) of the sarcoplasmic reticulum (SR) membrane that opens to release calcium from the SR into the cytoplasm. Different isoforms of both RyRs and DHPRs exist in cardiac and skeletal muscle cells. In particular, the RyR1 and DHPR-isoform 3 are predominant in skeletal muscle and the RyR2 and DBPR-isoform 1 are predominant in cardiac cells. There is only about 70% identity between RyR1 and RyR2 amino acid sequences. In skeletal muscle, it is known that the ryanodine receptor (RyR1) is activated by a protein-protein interaction with a 138 amino acid cytoplasmic loop between repeats II and III of the DHPR α-1 subunit (Tanabe et al., 1990 , Nature 346:567-568). A region of the skeletal DHPR cytoplasmic loop that is sufficient to activate skeletal muscle RyR1-mediated calcium release has been determined to reside within 20 amino acids from Thr 671 to Leu 690 (El Hayek et al., 1995 , J. Biol. Chem. 270:22116-22118; Dulhunty et al., 1999 , Biophys. J. 77:189-203; and Gurrola et al., 1999 , J. Biol. Chem. 274:7879-7886). There are four DHPR molecules located in a tetrad configuration of DHPRs opposite every second RyR1 polypeptide in skeletal muscle, in a strict geometrical alignment that is considered to be important for normal excitation-contraction coupling. During excitation of the DHPR, such as by electrical stimulation, this protein-protein interaction presumably induces a conformational shift in the RyR1 polypeptide that results in channel opening, thereby causing calcium efflux from the SR. Accordingly, excitation-contraction coupling in skeletal muscle is essentially a calcium-independent process. In contrast, excitation-contraction coupling in cardiac muscle involves a calcium-induced calcium release (CICR) mechanism (Niggli, 1999 , Annu Rev Physiol 61:311-335). The opening of cardiac DHPR calcium channels following their excitation results in a small amount of extracellular calcium influx into cardiac myocytes via the voltage-dependent L-type calcium channels (i.e. cardiac DHPRs) that are activated during each action potential. This initial signal acts as a trigger for subsequent CICR from the intracellular calcium stores in the SR. The secondary calcium release from the SR occurs via the cardiac RyR2 calcium release channels. In most mammals, CICR amplifies the initial signal trigger several-fold, consistent with the stoichiometry of cardiac RyR2 molecules to cardiac DHPR of about 16:1. Notwithstanding that cardiac CICR requires an initial elevation of cytosolic Ca 2+ to trigger calcium release from the SR, it does not appear to become self-sustaining. This is because CICR possibly propagates only between cardiac myocytes that are overloaded with calcium, however is normally localized to individual cells. Additionally, the force of cardiac muscle contraction increases proportionately with [Ca 2+ ] i between about 3×10 −7 M [Ca 2+ ] i and about 10 −6 M [Ca 2+ ] I , suggesting that CICR is not an all or nothing response. In contrast to excitation-contraction coupling in skeletal myocytes, it is not known whether or not there is any direct protein-protein interaction between cardiac DHPR and cardiac RyR2 in vivo, however the cytoplasmic loop of the skeletal DHPR α-1 subunit does bind to cardiac RyR2 in two hybrid assays (Osterland et al., 1999 , Biophys. J. 76:A467-(abstract)) and the 20-mer peptide (i.e. Thr 671 to Leu 690 ) of the skeletal DHPR α-1 subunit cytoplasmic loop binds to RyR2 in surface plasmon resonance studies (O'Reilly and Ronjat, 1999 , Biophys. J. 76:A466-(abstract)). Compelling data indicate that the relationship between skeletal and cardiac DHPRs and RyRs channels is different. For example, cardiac RyR2 expressed in dyspedic myocytes that lack skeletal RyR1 but contain skeletal DHPR α-1 subunit, cannot support skeletal type excitation-contraction coupling. Additionally, isolated RyR2 channels are not activated by the entire 138-amino acid cytoplasmic loop between repeats II and III of cardiac or skeletal DHPR α-1 subunits (Lu et al., 1994 , J. Biol. Chem. 269:6511-6516). Additionally, the 20-mer peptide (i.e. Thr 671 to Leu 690 ) of the skeletal DHPR α-1 subunit cytoplasmic loop has been shown not to induce Ca 2+ release from cardiac SR, or to enhance [ 3 H]ryanodine binding to cardiac RyR2 channels (El Hayek, et al., 1995, supra), despite the fact that it is a high affinity activator of skeletal muscle RyR1 channels. Moreover, these available data suggest that the 20-mer peptide (i.e. Thr 671 to Leu 690 ) of the skeletal DHPR α-1 subunit cytoplasmic loop cannot activate cardiac RyR2 channels, such as, for example, by prolonging their open time or frequency of opening. Stern (1992 , FASEB J. 6:3092-3100) proposed that Ca 2+ synapses (i.e. localized domains of very high Ca 2+ near the site of Ca 2+ entry and release) functionally link the activities of DHPRs and RyRs in cardiac tissue. Each Ca 2+ synapse allows local control of the RyR2 by virtue of the high local Ca 2+ concentration, so as to produce the observed high signal amplification without spreading of the Ca 2+ release signal across the entire cell or between cells. As a consequence, the number of release units recruited during each signal could be quantitatively graded with the trigger calcium release. This proposal is consistent with the observation of calcium sparks of short duration (about 50 ms) and limited spatial spread (about 1.5 μm) during stimulation of cardiac myocytes (Cheng et al., 1993 , Science 262:740-744). Myocardial contractile failure is a common cause of morbidity and mortality in patients with ischemic heart disease, congestive heart failure, and systemic inflammatory states such as sepsis. Accumulating evidence indicates that contractile failure is associated with dysregulation of myoplasmic calcium flux. Reduced Ca 2+ sensitivity of the myofilaments or a deterioration of calcium signalling, such as, for example, by deterioration or disruption of the calcium synapse, deterioration of the RyR2, or deterioration of the DHPR, may lead to a decline in the force of cardiac contractions. Several Ca 2+ signal pathways are adversely affected during cardiac failure or cardiac hypertrophy (with calcium overload observed in end-stage heart failure). An elevated resting Ca 2+ concentration, reduced Ca 2+ transient amplitude, slowed relaxation, and altered Ca 2+ pump in the SR have been observed in failing or hypertrophic cardiac tissue. More particularly, hypertrophied as well as failing hearts show decreased excitation-contraction coupling efficiencies compared to normal hearts (Gomez et al., 1997 , Science 276:755-756). However, individual DHPRs and RyRs in failing or hypertrophic hearts appear normal, suggesting that the link between these two calcium signal proteins may be defective. This view is supported by the restoration of normal excitation-contraction coupling in hypertrophic cells or following congestive heart failure by the application of β-adrenergic agonists to prolong the open time of cardiac DHPRs. Additionally, hyperphosphorylation of RyR2 in failing human hearts results in defective channel function. In addition, cardiac output can be boosted in acute situations, such as after heart attack, by “inotropic agents” that enhance excitation-contraction coupling. Discrete areas of heart muscle are damaged during ischaemic episodes, causing reduced cardiac output. Blood supply to essential organs such as the brain can be maintained by asking the remaining healthy heart muscle to contract more strongly. This is currently done by drugs which mimic beta adrenergic stimulation and increase cAMP levels to stimulate DHPR activity and excitation-contraction coupling. In the long term increased cAMP levels can become toxic and lead to calcium overload. |
<SOH> SUMMARY OF THE INVENTION <EOH>This specification contains nucleotide and amino acid sequence information prepared using the program PatentIn Version 3.1, presented herein after the bibliography. Each nucleotide or amino acid sequence is identified in the sequence listing by the numeric indicator <210> followed by the sequence identifier (e.g. <210>1, <210>2, etc). The length, type of sequence (DNA, protein (PRT), etc) and source organism for each nucleotide or amino acid sequence are indicated by information provided in the numeric indicator fields <211>, <212> and <213>, respectively. Nucleotide and amino acid sequences referred to in the specification are defined by descriptor “SEQ ID NO:” followed by the numeric identifier. For example, SEQ ID NO: 1 refers to the information provided in the numeric indicator field designated <400>1, etc. Reference herein to the consensus sequence set forth in SEQ ID NO: 1 shall be taken to include a reference to any one or more of the amino acid sequences set forth in SEQ ID Nos: 2-7 used to compile said consensus sequence. Throughout this specification, unless the context requires otherwise, the word “comprise”, or variations such as “comprises” or “comprising”, will be understood to imply the inclusion of a stated step or element or integer or group of steps or elements or integers but not the exclusion of any other step or element or integer or group of elements or integers. As used herein the term “derived from” shall be taken to indicate that a specified integer may be obtained from a particular source albeit not necessarily directly from that source. In work leading up to the present invention, the inventors sought to identify novel means for modulating CICR in cardiac tissue, so as to provide for improved treatment regimes for cardiac failure and/or cardiac hypertrophy. Surprisingly, although no physical connection between cardiac DHPRs and cardiac RyRs has been established, the present invention provides small fragments of the skeletal or cardiac DHPR polypeptides, such as, for example, small basic charged peptides, that can activate cardiac RyR2 channels. More particularly, the present inventors have shown that the 20-mer peptide (i.e. Thr 671 to Leu 690 ) of the skeletal DHPR α-1 subunit cytoplasmic loop produces significant activation of RyR2 channels at −40 mV (negative potentials induce calcium release from the SR) and strong inhibition at +40 mV. Activation of cardiac RyR2 was observed at concentrations as low as 1 nM peptide, significantly less than the peptide concentration required to activate skeletal muscle RyR1. Additionally, the inhibition of cardiac RyR2 channels was significantly greater than that observed for skeletal RyR1 channels at 3×10 −7 M cytoplasmic Ca 2+ . Accordingly, one aspect of the present invention provides a method for modulating the activity of a cardiac ryanodine receptor (RyR2) calcium channel comprising contacting a cardiac RyR2 with an amount of a fragment of a dihydropyridine receptor (DHPR) polypeptide, such as, for example, a basic charged fragment, sufficient to modulate the activity of said RyR2. More preferably, the present invention provides a method for modulating the activity of a cardiac ryanodine receptor (RyR2) calcium channel comprising contacting a cardiac RyR2 with an amount of a fragment of a dihydropyridine receptor (DHPR) polypeptide, such as, for example, a basic charged fragment, sufficient to modulate the activity of said RyR2, and determining the activity of said cardiac RyR2 calcium channel. It will be apparent from the preceding discussion that one embodiment of the invention is directed to a method for enhancing the activity of a cardiac RyR2 calcium channel comprising contacting a cardiac RyR2 with an amount of a fragment of a dihydropyridine receptor (DHPR) polypeptide sufficient to enhance the activity of said RyR2, and determining the activity of said cardiac RyR2 calcium channel. As exemplified herein and without limiting the invention to any theory or mode of action or effective peptide concentration, the present inventors have shown that, for isolated cardiac RyR2 in a lipid bilayer, both the frequency of channel openings and the duration of each channel opening is enhanced by the application of up to about 1 nM peptide to about 10 μM peptide. At high peptide concentrations, the activity of channels that opened first declines slightly however the activity of other channels is more pronounced, presumably reflecting a microheterogeneity in RyR2 channel sensitivities to peptide. It will also be apparent from the preceding discussion that another embodiment of the invention is directed to a method for inhibiting the activity of a cardiac RyR2 calcium channel comprising contacting a cardiac RyR2 with an amount of a fragment of a dihydropyridine receptor (DHPR) polypeptide sufficient to inhibit the activity of said RyR2, and determining that said cardiac RyR2 calcium channel lacks activity. As exemplified herein and without limiting the invention to any theory or mode of action or effective peptide concentration, the present inventors have shown that, for isolated cardiac RyR2 in a lipid bilayer, the frequency of channel openings particularly at +40 mV is reduced by a concentration in excess of about 10 μM peptide, possibly as a consequence of peptide binding within the pore of the RyR2 channel at a site that is distinct from the site at which it binds during channel activation. A second aspect of the invention provides a method for identifying a peptide modulator of a cardiac RyR2 calcium channel comprising: (i) incubating an amount of a fragment of a dihydropyridine receptor polypeptide or a homologue, analogue or derivative thereof that modulates cardiac RyR2 channel activity in the presence of a functional cardiac RyR2 calcium channel under conditions appropriate for calcium channel activity to be modulated and determining the activity of the channel; (ii) incubating a candidate peptide in the presence of said functional cardiac RyR2 calcium channel under conditions appropriate for calcium channel activity to be modulated by said dihydropyridine receptor polypeptide or a homologue, analogue or derivative thereof and determining the activity of the channel; (iii) comparing the activity at (i) and (ii); and (iv) preferably selecting those peptides having comparable or enhanced modulation of channel activity at (ii) relative to (i). In an alternative embodiment, this aspect of the invention provides a method for identifying a peptide modulator of a cardiac RyR2 calcium channel comprising: (i) incubating an amount of a fragment of a dihydropyridine receptor polypeptide or a homologue, analogue or derivative thereof that modulates cardiac RyR2 channel activity in the presence of a functional cardiac RyR calcium channel under conditions appropriate for calcium channel activity to be modulated and determining the activity of the channel; (ii) incubating a candidate peptide and an amount of said dihydropyridine receptor polypeptide or a homologue, analogue or derivative thereof that modulates cardiac RyR2 channel activity in the presence of a functional cardiac RyR2 calcium channel under conditions appropriate for calcium channel activity to be modulated by said dihydropyridine receptor polypeptide or a homologue, analogue or derivative thereof and determining the activity of the channel; (iii) comparing the activity at (i) and (ii); and (iv) preferably selecting those peptides having comparable or enhanced modulation of channel activity at (ii) relative to (i). A third aspect of the present invention provides a method of determining whether a cardiac RyR2 channel is open or has a high channel open probability said method comprising contacting a cardiac RyR2 channel with an amount of a fragment of a dihydropyridine receptor (DHPR) polypeptide or homologue, analogue or derivative for a time and under conditions sufficient for binding to said channel to occur and determining the binding of said peptide to said channel, wherein binding of said peptide to said channel indicates a high channel open probability and wherein non-specific peptide binding indicates a low channel open probability. A fourth aspect of the present invention provides a method of treatment of cardiac dysfunction in a human or animal subject comprising administering an effective amount of a fragment of a dihydropyridine receptor (DHPR) polypeptide or homologue, analogue or derivative for a time and under conditions sufficient for enhanced cardiac contraction to occur thereby rectifying said cardiac dysfunction. A fifth aspect of the present invention provides a pharmaceutical composition comprising a fragment of a dihydropyridine receptor polypeptide, which peptide comprises at least about 5 contiguous amino acid residues of the peptide set forth in any one of SEQ ID NOs: 1-10 or a homologue, analogue or derivative thereof together with one or more pharmaceutically acceptable diluents. Single and three letter abbreviations used throughout the specification are defined in Table 1. TABLE 1 Single and three letter amino acid abbreviations Three-letter One-letter Amino Acid Abbreviation Symbol Alanine Ala A Arginine Arg R Asparagine Asn N Aspartic acid Asp D Cysteine Cys C Glutamine Gln Q Glutamic acid Glu E Glycine Gly G Histidine His H Isoleucine Ile I Leucine Leu L Lysine Lys K Methionine Met M Phenylalanine Phe F Proline Pro P Serine Ser S Threonine Thr T Tryptophan Trp W Tyrosine Tyr Y Valine Val V Any residue or as Xaa X otherwise defined |
Arrayed waveguide interferometer |
The invention relates to an arrayed waveguide interferometer, which can be used as core components for optical communication network, optical information transmission, spectrum measurement, sensors, laser devices or integrated photoelectric devices. The arrayed waveguide interferometer includes an input-waveguide, an output-waveguide and a waveguide-array which acts as a coupling component between the input-waveguide and the output-waveguide. All of the optical waveguides are formed in a corporeal carrier, and haves straight-line shape and/or curve shape. |
1. An arrayed waveguide interferometer comprising an input-waveguide, an output-waveguide, and a waveguide-array which acts as a coupling component between the input-waveguide and the output-waveguide, wherein said waveguide-array composed of at least two optical waveguides and formed on a carrier, and said carrier is a plane substrate. 2. The arrayed waveguide interferometer according to claim 1, wherein the optical path difference of optical waves which are input from the input end of the input-waveguide and reach the output end of the output waveguide via two adjacent optical waveguides in the waveguide-array is a multiple of the wavelength of the optical wave to be output from the output-waveguide. 3. The arrayed waveguide interferometer according to claim 0.1, wherein the optical path difference of optical waves which_are input from the input end of the input-waveguide and reach the output end of the output-waveguide via two adjacent optical waveguides in the waveguide-array is an integral multiple of the wavelength of the optical wave to be output from the output-waveguide. 4. The arrayed waveguide interferometer according to claim 1, wherein the optical waveguides in the waveguide-array, the input-waveguide, and the output-waveguide are straight-line type of optical waveguides, and the range of the crossing angle between the input-waveguide and output-waveguide is from 0 to 180 degree. 5. The arrayed waveguide interferometer according to claim 1, wherein the optical waveguides in the waveguide-array are curve type of optical waveguides, the input-waveguide and the output-waveguide are straight-line type of optical waveguides, and the range of the crossing angle between the input-waveguide and output-waveguide is from 0 to 360 degree. 6. The arrayed waveguide interferometer according to claim 1, wherein parts of the optical waveguides in the waveguide-array, the input-waveguide, and the output-waveguide are straight-line type of optical waveguides and the other parts are curve type of optical waveguides. 7. The arrayed waveguide interferometer according to claim 1, wherein all the optical waveguides in the waveguide-array, the input-waveguide, and the output-waveguide are curve type of optical waveguides. 8. The arrayed waveguide interferometer according to claim 1, wherein the carrier is a three-dimensional structure. |
<SOH> BACKGROUND OF THE INVENTION <EOH>Conventional interferometer includes Fabry-Perot interferometer, Mach-Zehnder interferometer, Michelson interferometer and so on which have been wildly used in various technical fields such as spectrum analysis, laser devices, precise measurement, and photoelasticity analysis. A lot of fiber sensors such as fiber-stress-sensor, fiber-strain-sensor, fiber-temperature-sensor, fiber-magnetic-field-sensor and the like also use sensibility-enhanced fiber as a part of above mentioned interferometer to carry out sensing. In recent years, as the development of optical communication network, there exists the need to various active and passive optical components, such as wavelength demultiplexer/multiplexer (WDMUX/WMUX), wavelength-selective switches (WSS), wavelength-selective router (WSR), wavelength-selective coupler (WSC), wavelength add/drop multiplexer (WADM), optical isolator, narrow band high-stable laser, etc. However, above applications have strict requirements to a lot of parameters such as channel space, the number of total channels, insertion loss, return loss, degree of channel isolation, size of components and compatibility with fibers and the like. Conventional interferometers could not sufficiently satisfy those requirements. For example, the wavelength demultiplexer made of Fabry-Perot interferometer may achieve very high wavelength resolution because it depends on multi-beam interference. However, one demultiplexer of above described type corresponds to only one channel. The degree of integration of this type of wavelength demultiplexer is low and the insertion loss is relatively high. As waveguide Mach-Zehnder interferometer and Michelson. Interferometer employ double-beam interference, their wavelength resolutions are low. The multiplexer/demultiplexer made of waveguide Mach-Zehnder interferometer need a channel space of more than 10 nm, which confines its use in double wavelength system or systems with large channel space. Further, if multilayer interference filters are made to achieve the effect of narrow band filter that meet the requirements of optical communication network, such a filter will suffer the disadvantages of complex structure, high cost, large size and low integration. Therefore, the number of channels will be limited. Above disadvantages limit the application of conventional interferometers in optical communication. Thus, a lot of new components, for example, arrayed waveguide grating (AWG), fiber Bragg-grating (FBG) and the like, have been developed for optical communication network. Among these new components, AWG generates optical path difference by means of waveguide-array so that optical waves having different wavelength may separately diffract in space and then couple into different channels. However, AWG does not have a modularized structure although it can contain more number of optical channels. FBG periodically modulates its refractive index along the axial direction of the fiber and generates Bragg-reflection. FBG is a narrow stop band filter or a narrow band reflector and has a modularized structure. Only one FBG is added if the adding of one channel is needed. However, such a FBG have to be manufactured with special processing technique so as to modulate its refractive index. |
<SOH> SUMMARY OF THE INVENTION <EOH>The present invention has been developed to overcome above disadvantages in prior art. It is therefore an object of the present invention to provide an arrayed waveguide interferometer which is capable of constructing various optical network devices, sensing devices, optical spectrum measuring instruments, laser devices, integrated opto-electronic devices and the like so that the problem of building narrow band waveguide-type interferometers can be solved. To achieve above object, according to an aspect of the present invention, an arrayed waveguide interferometer comprises an input-waveguide, an output-waveguide, and a waveguide-array which acts as a coupling component between the input-waveguide and the output-waveguide, wherein said waveguide-array composed of at least two optical waveguides and formed on a carrier, and said carrier is a plane substrate. Preferably, the optical path difference of optical waves which are input from the input end of the input-waveguide and reach the output end of the output-waveguide via two adjacent optical waveguides in the waveguide-array is a multiple of the wavelength of the optical wave to be output from the output-waveguide. Preferably, the optical path difference of optical waves which are input from the input end of the input-waveguide and reach the output end of the output-waveguide via two adjacent optical waveguides in the waveguide-array is an integral multiple of the wavelength of the optical wave to be output from the output-waveguide. Preferably, the optical waveguides in the waveguide-array, the input-waveguide, and the output-waveguide are straight-line type of optical waveguides, and the range of the crossing angle between the input-waveguide and output-waveguide is from 0 to 180 degree. Preferably, the optical waveguides in the waveguide-array are curve type of optical waveguides, and the input-waveguide and the output-waveguide are straight-line type of optical waveguides, and the range of the crossing angle between the input-waveguide and output-waveguide is from 0 to 360 degree. Preferably, parts of the optical waveguides in the waveguide-array, the input-waveguide, and the output-waveguide are straight-line type of optical waveguides and the other parts are curve type of optical waveguides. Preferably, all the optical waveguides in the waveguide-array, the input-waveguide, and the output-waveguide are curve type of optical waveguides The carrier may be a three-dimensional structure. Next, the principle of the present invention will be described. Optical waves in the input-waveguide are coupled to the output-waveguide by means of the waveguide-array that consists at least two optical waveguides. Each optical waveguide in the waveguide-array introduces a certain optical path difference. Therefore, all beams of optical waves are interferentially overlapped in the output-waveguide. Only the optical wave of which wavelength meet a certain conditions can generate constructive interference, and comes out from the output-waveguides. Therefore, this kind of interferometer is called as arrayed waveguide interferometer (AWI) based on such a structure characteristic. Unlike AWG, the arrayed waveguide interferometers according to the present invention depends on multi-beam interference, but not multi-beam diffraction. The arrayed waveguide interferometers of the present invention can achieve very high wavelength resolution due to multi-beam interference. The wavelength resolution of the arrayed waveguide interferometers may typically be 1/n of the output center wavelength, where n is the number of optical waveguides contained in the waveguide-array. In the case where the output center wavelength is 1500 nm, the number of optical waveguides contained in the waveguide-array typically is 10,000 so as to obtain a wavelength resolution of 0.15 nm. The arrayed waveguide interferometer according to the present invention provides following advantages and effects in comparison to the prior art. The arrayed waveguide interferometers of the present invention use multi-beam interference such that the interferometers can obtain very high wavelength resolution and very narrow channels space. Further, modularization structure is achieved such that only one module is added if the adding of one channel is needed. For the same device, insertion loss due to interfaces between components does not increase as the number of the channel increases. Furthermore, the arrayed waveguide interferometers of the present invention can be used to constitute various optical network devices, sensors, and measuring instruments, such as optical wave multiplexers/demultiplexers, optical switches, couplers, routers, optical isolators, optical spectrum analyzer, sensors, and reflectors. The arrayed waveguide interferometers can be volume produced by using of optical mask technique used in large scale integrated circuit, thereby reducing the size and ensuring good repeatability. |
Molded polyester for housing |
A biodegradable plastic material that can provide long-term reliability, even though being formed of a biodegradable polyester material, and a shaped article obtained therefrom. A biodegradable plastic material is treated with a compound being capable of reacting with active hydrogen in the biodegradable plastic, and a shaped biodegradable plastic article obtained from the material. |
1. A biodegradable plastic material that is treated with a compound capable of reacting with active hydrogen in the biodegradable plastic material. 2. The biodegradable plastic material according to claim 1, characterized by being a biodegradable polyester material. 3. The biodegradable plastic material according to claim 1, characterized by being a copolymer of a biodegradable polyester and a biodegradable polymer having an amino group or/and an amide linkage, or a mixture of a biodegradable polyester and a biodegradable polymer having an amino group or/and an amide linkage. 4. The biodegradable plastic material according to claim 1, characterized in that said biodegradable plastic material treated with a compound capable of reacting with active hydrogen has an acid value of 0.5 or less. 5. The biodegradable plastic material according to claim 1, characterized in that, after aging for 48 hours under conditions at a constant temperature and at a constant humidity in which the temperature is 80° C. and the relative humidity is 80%, an increase of an acid value is 0.2 or less and a lowering of a molecular weight is 10% or less. 6. The biodegradable plastic material according to claim 1, characterized in that the active hydrogen is derived from one atomic group or two or more atomic groups selected from a carboxyl group, a hydroxyl group, an amino group, and an amide linkage in the biodegradable plastic material. 7. The biodegradable plastic material according to claim 1, characterized in that said compound capable of reacting with active hydrogen is a crosslinking agent having a carbodiimide group. 8. The biodegradable plastic material according to claim 7, characterized in that said crosslinking agent having a carbodiimide group is dicyclohexylcarbodiimide or diisopropylcarbodiimide. 9. The biodegradable plastic material according to claim 1, characterized by containing a silicate. 10. The biodegradable plastic material according to claim 9, characterized in that said silicate has a silicon dioxide content of 50% or more. 11. The biodegradable plastic material according to claim 9, characterized in that said silicate is in a form of particles having a mean particle size of 50 μm or less. 12. A shaped biodegradable plastic article that is obtained by shaping a biodegradable plastic material treated with a compound capable of reacting with active hydrogen in the biodegradable plastic material. 13. The shaped biodegradable plastic article according to claim 12, characterized in that said biodegradable plastic material is a biodegradable polyester material. 14. The shaped biodegradable plastic article according to claim 12, characterized in that said biodegradable plastic material is a copolymer of a biodegradable polyester and a biodegradable polymer having an amino group or/and an amide linkage, or a mixture of a biodegradable polyester and a biodegradable polymer having an amino group or/and an amide linkage. 15. The shaped biodegradable plastic article according to claim 12, characterized by being a housing for an electrical appliance. 16. The shaped biodegradable plastic article according to claim 12, characterized in that said biodegradable plastic material treated with a compound capable of reacting with active hydrogen has an acid value of 0.5 or less. 17. The shaped biodegradable plastic article according to claim 12, characterized in that, after aging for 48 hours under conditions at a constant temperature and at a constant humidity in which the temperature is 80° C. and the relative humidity is 80%, an increase of an acid value is 0.2 or less and a lowering of a molecular weight is 10% or less. 18. The shaped biodegradable plastic article according to claim 12, characterized in that the active hydrogen is derived from one atomic group or two or more atomic groups selected from a carboxyl group, a hydroxyl group, an amino group, and an amide linkage in the biodegradable plastic material. 19. The shaped biodegradable plastic article according to claim 12, characterized in that said compound capable of reacting with active hydrogen is a crosslinking agent having a carbodiimide group. 20. The shaped biodegradable plastic article according to claim 19, characterized in that said crosslinking agent having a carbodiimide group is dicyclohexylcarbodiimide or diisopropylcarbodiimide. 21. The shaped biodegradable plastic article according to claim 12, characterized by containing a silicate. 22. The shaped biodegradable plastic article according to claim 21, characterized in that said silicate has a silicon dioxide content of 50% or more. 23. The shaped biodegradable plastic article according to claim 21, characterized in that said silicate is in a form of particles having a mean particle size of 50 μm or less. 24. A method for producing a shaped biodegradable plastic article, characterized by shaping a mixture obtained by adding and mixing a compound capable of reacting with active hydrogen to a biodegradable plastic material before, during, or after being molten. 25. The method for producing a shaped biodegradable plastic article according to claim 24, characterized in that said shaping is conducted by one of film extrusion, extrusion, and injection molding. 26. A method for producing a shaped biodegradable plastic article, characterized by shaping a resultant mixture obtained by adding a compound capable of reacting with active hydrogen and a silicate, simultaneously or individually, to a biodegradable plastic material before, during, or after being molten and mixing. 27. The method for producing a shaped biodegradable plastic article according to claim 26, characterized in that said shaping is conducted by one of film extrusion, extrusion, and injection molding. 28. The method for producing a shaped biodegradable plastic article according to claim 26, characterized in that said silicate has a silicon dioxide content of 50% or more. 29. The method for producing a shaped biodegradable plastic article according to claim 26, characterized in that said silicate is in a form of particles having a mean particle size of 50 μm or less. |
<SOH> BACKGROUND ART <EOH>Plastics penetrate any fields of life and industry, and the production rate of plastics has reached about 100,000,000 tons in the world per year. Most of the used plastics are disposed of, and it is regarded as one cause of disturbing the environment of the earth. Currently, as a method for solving this problem, plastic recycling and utilization of biodegradable polymers are most attracting attention. With respect to the plastic recycling, “The Household Appliances Recycling Law” was enforced in April, 2001 for recycling used electric appliances, but almost no recovery or recycling is carried out in waste of household electric appliances other than the four types of large-size electric appliances, i.e., television sets, refrigerators, air-conditioners, and washing machines, and there is no regal regulations. For this reason, almost all used electric appliances are disposed of as non-combustible waste. A great number of appliances sold even in a small size result in much waste collectively. There is now a lack of places for disposing of waste and therefore the above fact is a serious problem. As an example of a method for disposing of waste usually employed currently, there is a method of shredding waste. However, the disposing of waste by shredding merely reduces the volume of the waste, and, when the resultant waste shredded is buried in the ground, it remains as it is for several tens years or hundreds years, and hence the problem is not fundamentally solved. When shreds are presumed to be recycled as materials, all parts are together ground into small pieces and therefore, for example, useful materials, such as copper, are mixed with other less useful materials and hence reduced in purity, leading to a disadvantage in that the recovery efficiency is low. On the other hand, it is considered that utilization of biodegradable polymers has the following two advantages. The first one is that, when an electric appliance has a structure such that a housing or structure body part formed from a biodegradable material, which occupies most of the volume of the electric appliance, and non-biodegradable parts, such as electronic parts, substrates, and the like, are joined together by, for example, a screw or a inserting structure, and they are easily separated from each other, parts to be recycled and parts which can be disposed of as they are can be individually dealt with by dismounting the electric appliance to some extent, and therefore it is expected that the recovery efficiency is increased. The second one is that, when the top surface of a housing for, for example, radio sets, microphones, hanging-type TV sets, keyboards, Walkmans, portable phones, radio cassette players, or earphones is formed from a biodegradable material, that is, a portion that a human body is frequently in contact with is formed from a biodegradable material, there can be provided electric appliances having excellent safety, as compared to ones using synthetic resins. However, all types of biodegradable polymers cannot be used in the above applications, and those to be used in a housing and structure materials for electric appliances must have physical properties required for the applications. The present inventors have found that it is a requirement that no lowering of the physical properties occur after the biodegradable polymer is held in an atmosphere in which, for example, the temperature is 80° C. and the humidity is 80% for 48 hours. The biodegradable polymer is an organic material which is decomposed by action of the natural world or the living organisms and assimilated, and it has been developed as an ideal material acclimatized to the environment. Examples of biodegradable polymers include polysaccharide derivatives, such as cellulose, starch, dextran, and chitin; peptides, such as collagen, casein, fibrin, and gelatin; polyamino acids; polyvinyl alcohol; polyamide, such as nylon 4 and a nylon 2-nylon 6 copolymer; and aliphatic polyester. Aliphatic polyester resins as representative examples of biodegradable polymers generally have a lower melting point, and hence do not have satisfactory physical properties (especially heat resistance and impact resistance) suitable for practical shaped articles. Therefore, various studies are made on addition of inorganic filler, improvement of the crystallization rate by addition of a crystal nucleating agent, and blend of a biodegradable resin having elastic properties with a lower glass transition point, and, with respect to the shaped articles using these plastics, several patent applications have already been filed (e.g., Unexamined Japanese Patent Application Laid-Open Specification Nos. Hei 3-290461, Hei 4-146952, and Hei 4-325526). These shaped articles are used in films and packaging materials, which do not particularly require durability. On the other hand, in the application of biodegradable aliphatic polyester resins to housing for electric appliances, electronic appliances and the like, not only heat resistance but also long-term reliability (durability under conditions at a constant temperature and at a constant humidity) are required. Electric appliances and electronic appliances individually have different duration of the product life, and small-size audio products must maintain their physical properties for 3 to 7 years under conditions at a relative humidity of 80% at 30° C. Taking into consideration the conditions under which electric appliances and electronic appliances are used at various temperatures and humidity, general biodegradable polyester has a problem of long-term reliability as mentioned above, and therefore cannot be used in the housing for electric appliances, electronic appliances, and the like. Currently, biodegradable polymers, especially aliphatic polyester resins are being utilized as materials in agriculture, forestry, and fisheries (e.g., film, plant pot, fishing line, and fish net), materials in civil engineering works (e.g., water retention sheet, plant net, and sandbag), and the fields of packaging and container (difficult to recycle since soil and food adhere to them). When using the biodegradable polyester resins in the housing for electric appliances and electronic appliances, it is a minimum requirement that no lowering of the physical properties occur for 48 hours or longer under conditions at a constant temperature and at a constant humidity (such that, for example, the temperature is 80° C. and the relative humidity is 80%) as mentioned above. In general biodegradable polyester, for example, polylactic acid having most excellent heat resistance, when the shaped article is subjected to aging test at a temperature of 80° C. at a relative humidity of 80% for 48 hours, the molecular weight is 60% lowered due to hydrolysis (see Comparative Example 1 below), so that the application of this polyester to housing materials for household electric appliances is difficult. As a cause of the lowering of the physical properties, i.e., hydrolysis, it is known that, for example, in polyester, a carboxyl group at a terminal of a polymer chain catalytically hydrolyzes an ester linkage in a molecular chain. The present inventors have attempted to create a plastic material which is advantageous not only in that, for securing long-term reliability, active hydrogen in a functional group having active hydrogen in the biodegradable plastic, such as a carboxyl group or a hydroxyl group, is inhibited from catalytically hydrolyzing a main chain during use of the product comprised of the plastic material to maintain the physical properties (e.g., strength, hydrolysis resistance, and heat resistance), but also in that the plastic material is decomposed after being disposed of due to hydrolysis and microorganisms generally present in the natural world. It is an object of the present invention to provide a biodegradable plastic material which can secure long-term reliability, particularly a biodegradable polyester material, and further a shaped article obtained therefrom. |
<SOH> BRIEF DESCRIPTION OF THE DRAWINGS <EOH>FIG. 1A is a graph obtained by plotting the time (day) and the temperature (° C.) where an increase of an acid value is 0.2 or less and lowering of a molecular weight is 10% or less in Example 5. FIG. 1B is a graph obtained by plotting a logarithm of the time (log(day)) and a reciprocal of the temperature (1/temperature: 1/K) where the increase of the acid value is 0.2 or less and the lowering of the molecular weight is 10% or less in Example 5. FIG. 2A is a graph obtained by plotting the time (day) and the temperature (° C.) where an increase of an acid value is 0.2 or less and lowering of a molecular weight is 10% or less in Example 6. FIG. 2B is a graph obtained by plotting a logarithm of the time (log(day)) and a reciprocal of the temperature (1/temperature: 1/K) where the increase of the acid value is 0.2 or less and the lowering of the molecular weight is 10% or less in Example 6. FIG. 3A is a graph obtained by plotting a change of the acid value versus the time (day) during which the physical properties of the biodegradable polyester are retained at individual temperatures in Example 6. In the figure, a solid square indicates the results in the aging at 85° C., an open rhomb at 80° C., an open triangle at 75° C., and an open square at 70° C. The relative humidity is 80%. FIG. 3B is a graph obtained by plotting a reduction rate (%) of the weight average molecular weight versus the time (day) during which the physical properties of the biodegradable polyester are retained at individual temperatures in Example 6. In the figure, the solid square indicates the results in the aging at 85° C., the open rhomb at 80° C., the open triangle at 75° C., and the open square at 70° C. The relative humidity is 80%. detailed-description description="Detailed Description" end="lead"? |
Cosmetic compositions containing a starch and an ester and the use thereof |
The present invention relates to a cosmetic composition comprising: a cosmetically acceptable medium, at least one starch and at least one ester selected from (1) liquid esters from a C3-C30 carboxylic acid and a C1-C30 alcohol, with at least one from the acid or the alcohol is branched or possesses at least one carbon-carbon double bond; and (2) esters from a C7-C30 aromatic acid having a carboxylic group that is directly linked to the aromatic ring, and a C1-C30 alcohol. The inventive composition is substantially free of soap. This composition has a “melting” texture and can be easily rinsed off. Hair treated with this composition has a soft feel with no residues. The inventive composition is preferably suitable for washing and/or conditioning keratinous materials, such as hair or skin. |
1. A cosmetic composition, comprising: a cosmetically acceptable medium, at least one starch, at least one carboxylic ester in an amount of up to 10% based on the weight of said cosmetic composition wherein said carboxylic ester is selected from 1) liquid esters of a C3-C30 carboxylic acid and a C1-C30 alcohol, wherein at least one of said acid or said alcohol is branched or possesses at least one carbon-carbon double bond, 2) esters of a C7-C30 aromatic acid and a C1-C30 alcohol, wherein said aromatic acid has carboxyl group directly bonded to said aromatic acid's ring; at least 30% by weight of water relative to the total weight of said composition, and up to 20% by weight of fatty phase relative to the total weight of said composition, with the provisos that said cosmetic composition is substantially free from fatty acid soap, said cosmetic composition is free of nonsilicone cationic polymer if said starch is a starch phosphate, and said carboxylic ester is not isopropyl palmitate or diisopropyl adipate, if said cosmetic composition further comprises at least one thickener and less than 3% by weight of surfactant relative to the weight of the composition. 2. The cosmetic composition of claim 1, wherein said starch is a corn starch, rice starch, manioc starch, tapioca starch, barley starch, potato starch, wheat starch, sorghum starch, or pea starch. 3. The cosmetic composition of claim 1, wherein said starch is modified by one or more of the following reactions. 4. The cosmetic composition of claim 1, wherein said starch is monostarch phosphates, distarch phosphates, tristarch phosphate or a mixture thereof. 5. The cosmetic composition of claim 1, wherein said starch is an amphoteric starch. 6. The cosmetic composition of claim 1, wherein said carboxylic ester is octyldodecyl behenate; isocetyl behenate; isocetyl lactate; isostearyl lactate; linoleyl lactate; oleyl lactate; isostearyl octanoate; isocetyl octanoate; decyl oleate; isocetyl isotearate; isocetyl laurate; isocetyl stearate; isodecyl octanoate; isodecyl oleate; isononyl isononanoate; isostearyl palmitate; myristyl isostearate; octyl isononanoate; 2-ethylhexyl isononate; octyl isostearate; octyldodecyl erucate; isopropyl palmitates, 2-ethylhexyl palmitate, 2-octyldecyl palmitate, branched alkyl myristates such as isopropyl myristate, t-butyl myristate, 2-octyldodecyl myristate, hexyl isostearate, butyl isostearate, isobutyl stearate; 2-hexyldecyl laurate; diisopropyl sebacate; diisopropyl adipate; diisostearyl adipate; octyldodecyl stearoyl stearate; pentaerythrityl tetraisononanoate; pentaerythrityl tetraisostearate; triisopropyl citrate; triisostearyl citrate; or trioctyldodecyl citrate. 7. The cosmetic composition of claim 6, wherein said carboxylic ester is isopropyl palmitate, 2-ethylhexyl palmitate, 2-octyldecyl palmitate, branched alkyl myristates such as isopropyl myristate, t-butyl myristate, and 2-octyldodecyl myristate, hexyl isostearate, butyl isostearate, isobutyl stearate; 2-hexyldecyl laurate, or isononyl isononanate. 8. The cosmetic composition according of claim 1, wherein said carboxylic ester is a C12-C15 alkyl benzoate, isostearyl benzoate, octyldodecyl benzoate, behenyl benzoate, or 2-ethylhexyl benzoate. 9. The cosmetic composition of claim 1, further comprising at least one hair benefit agent. 10. The cosmetic composition of claim 1, wherein said starch is present at a concentration ranging from 0.01% to 20% by weight relative to the total weight of the composition. 11. The cosmetic composition of claim 1, wherein said carboxylic ester is present at a concentration ranging from 0.001% to less than 10% by weight relative to the total weight of the composition. 12. The cosmetic composition of claim 9, wherein said hair benefit agent is present at a concentration ranging from 0.001% to 20% by weight relative to the total weight of the composition. 13. The cosmetic composition of claim 9, further comprising at least one surfactant selected from an anionic, nonionic, amphoteric, cationic surfactant or a mixtures thereof. 14. The cosmetic composition of claim 9, further comprising a cationic surfactant or a mixtures thereof. 15. The cosmetic composition of claim 13, wherein said surfactant is present at a concentration from 0.01% to 50% by weight relative to the total weight of the composition. 16. The cosmetic composition of claim 1, wherein said cosmetic composition is a shampoo, conditioner, composition for perming, straightening, coloring or bleaching the hair, rinse-off composition to be applied between the two steps of a perming or hair-straightening operation, styling gel, styling spray, styling mousse or washing composition for the body. 17. A method of washing or caring for keratinous materials by applying said cosmetic composition according to claim 1 to keratinous materials. 18. A method of treating or conditioning keratinous materials by applying said cosmetic composition according to claim 1 to keratinous materials. 19. The method of washing and caring keratinous materials of claim 17, wherein said cosmetic composition is a shampoo, conditioner, composition for perming, straightening, coloring or bleaching the hair, rinse-off composition to be applied between the two steps of perming or hair-straightening operation, gel, spray, mousse, lotion, cream emulsion or washing composition for body. 20. The method of washing or caring keratinous materials of claim 17, further comprising rinsing said cosmetic composition with water. 21. The method of washing and caring keratinous materials of claim 18, wherein said cosmetic composition is a shampoo, conditioner, composition for perming, straightening, coloring or bleaching the hair, rinse-off composition to be applied between the two steps of perming or hair-straightening operation, gel, spray, mousse, lotion, cream emulsion or washing composition for body. 22. The method of washing or caring keratinous materials of claim 18, further comprising rinsing said cosmetic composition with water. 23. The cosmetic composition of claim 1, wherein said at least one starch is a plurality of starches. 24. The cosmetic composition of claim 10, wherein said starch is present at a concentration ranging from 0.05% to 15% by weight relative to the total weight of the composition. 25. The cosmetic composition of claim 24, wherein said starch is present at a concentration ranging from 0.1% to 10% by weight relative to the total weight of the composition. 26. The cosmetic composition of claim 1, wherein said at least one carboxylic ester is a plurality of carboxylic esters. 27. The cosmetic composition of claim 11, wherein said carboxylic ester is present at a concentration ranging from 0.01% to 8% by weight relative to the total weight of the composition. 28. The cosmetic composition of claim 27, wherein said carboxylic ester is present at a concentration ranging from 0.05% to 6% by weight relative to the total weight of the composition. 29. The cosmetic composition of claim 9, wherein said at least one hair benefit agent is a plurality hair benefit agents. 30. The cosmetic composition of claim 12, wherein said hair benefit agent is present at a concentration ranging from 0.01% to 10% by weight relative to the total weight of the composition. 31. The cosmetic composition of claim 1, further comprising at least one surfactant selected from an anionic, nonionic, amphoteric, cationic surfactant or a mixture thereof. 32. The cosmetic composition according to claim 13, wherein said at least one surfactant is a plurality of surfactants. 33. The cosmetic composition of claim 31, wherein said at least one surfactant is a plurality of surfactants. 34. The cosmetic composition of claim 15, wherein said surfactant is present at a concentration ranging from 0.1% to 40% by weight relative to the total weight of the composition. 35. The cosmetic composition of claim 34, wherein said surfactant is present at a concentration ranging from 0.5% to 30% by weight relative to the total weight of the composition. 36. The cosmetic composition of claim 31, wherein said surfactant is present at a concentration ranging from 0.01% to 50% by weight relative to the total weight of the composition. 37. The cosmetic composition of claim 36, wherein said surfactant is present at a concentration ranging from 0.1% to 40% by weight relative to the total weight of the composition. 38. The cosmetic composition of claim 35, wherein said surfactant is present at a concentration ranging from 0.5% to 30% by weight relative to the total weight of the composition. 39. The cosmetic composition of claim 3, wherein said reaction is pregelatinization, oxidation, crosslinking, esterification or thermal treatment. 40. The cosmetic composition of claim 9, wherein said hair benefit agent is a vegetable oil, animal oil, mineral oil, synthetic oil, wax, ceramide, psedoceramide, silicone, cationic polymer, sunscreen or vitamin. 41. The method of washing or caring for keratinous materials of claim 17, wherein said cosmetic composition further comprises at least one hair benefit agent. 42. The method of washing or caring for keratinous materials of claim 41, wherein said cosmetic composition further comprises at least one surfactant. 43. The method of treating or conditioning keratinous materials of claim 18, wherein said cosmetic composition further comprises at least one hair benefit agent. 44. The method of treating or conditioning keratinous materials of claim 43, wherein said cosmetic composition further comprises at least one surfactant. 45. A method of washing or caring keratinous materials by applying said cosmetic composition of claim 9 to keratinous materials. 46. A method of washing or caring keratinous materials by applying said cosmetic composition of claim 13 to keratinous materials. 47. A method of treating or conditioning keratinous materials by applying said cosmetic composition of claim 9 to keratinous materials. 48. A method of treating or conditioning keratinous materials by applying said cosmetic composition of claim 13 to keratinous materials. 49. The cosmetic composition of claim 1, wherein a ratio of said liquid ester of a C3-C30 carboxylic acid and a C1-C30 alcohol to said starch is less than or equal to 1.5. 50. The cosmetic composition of claim 49, wherein said ratio is less than 1. 51. The cosmetic composition of claim 1, wherein a ratio of said ester of a C7-C30 aromatic acid and a C1-C30 alcohol to said starch is less than 2.5. 52. The cosmetic composition of claim 51, wherein said ratio is less than 2. 53. The cosmetic composition of claim 1, wherein said cosmetic composition has a pH of between 4 and 8. 54. The cosmetic composition of claim 53, wherein said pH is between 5 and 7. 55. The cosmetic composition of claim 13, further comprising at least one additive. 56. The cosmetic composition of claim 55, wherein said additive is a thickener, fragrance nacreous agent, preservative, silicone, nonsilicone sunscreen, vitamin, provitamin, anionic or nonionic polymer, protein, protein hydrolyzate, 18-methyleicosanoic acid, hydroxy acid, or panthenol. 57. The cosmetic composition of claim 56, wherein said additive is present at a concentration ranging from 0.001% to 20% by weight relative to the total weight of said cosmetic composition. 58. The cosmetic composition of claim 1, wherein said carboxylic ester is not isopropyl palmitate or diisopropyl adipate if said cosmetic composition further comprises a phosphorylated starch derivative, at least one thickener, and less than 3% by weight of surfactant relative to the weight of the composition. |
<SOH> BACKGROUND OF THE INVENTION <EOH>The present invention relates to new cosmetic compositions comprising: a cosmetically acceptable medium, at least one specific carboxylic ester, and at least one starch. It is well known that hair which has been sensitized (i.e., damaged and/or embrittled) to various degrees under the action of atmospheric agents or under the action of mechanical or chemical treatments, such as coloring, bleaching and/or perming, is often difficult to disentangle and to style, and lacks softness. Proposals have already been made for the treatment of keratin materials ,for example, hair with cosmetic compositions containing thickening polysaccharides such as, starch or celluloses. Such compositions, however, have drawbacks such as problems of rinsability, problems of stability to acidic pH, difficulties in distribution on the keratin materials, and inadequate cosmetic properties. Recommendations have already been made to use cationic polymers in compositions for washing or caring for keratin materials such as the hair in order to facilitate the disentangling of the hair and to impart to it softness and suppleness. The use of cationic polymers for this purpose presents a variety of drawbacks. Owing to their high affinity for the hair, some of these polymers are deposited to a substantial extent in the course of repeated uses, and lead to undesirable effects such as an unpleasant heavy feel, a stiffening of the hair, and an interfiber adhesion which impacts styling. Proposals have already been made to use oils such as vegetable or animal oils or else fatty acid esters as a conditioner. However, the keratin materials treated with these compositions usually have a critical greasy feel. In summary, it is found that state of the art cosmetic compositions do not give complete satisfaction. |
<SOH> SUMMARY OF THE INVENTION <EOH>The applicant has now found that the combination of a starch with a specific carboxylic ester allows these drawbacks to be remedied. Consequently, following the major research efforts, it has now been found by the applicant that the use of compositions, preferably haircare compositions, based on a specific ester and a starch allows the problems set out above to be limited or even suppressed. The hair is easy to disentangle and is smooth from root to tip, with an improvement in the hold of the style. Moreover, this combination imparts a “melting” texture to the cosmetic compositions: that is, a texture which disappears rapidly into the hair. Hair treated with this composition has a soft feel with no residues. Moreover, the compositions of the invention, when applied to the skin, for example, in the form of a foam bath or shower gel, provide an improvement in the softness of the skin. One aspect of the present invention provides new cosmetic compositions comprising: a cosmetically acceptable aqueous medium; at least one starch; at least one carboxylic ester in an amount of up to 10% based on the weight of the cosmetic composition wherein the carboxylic ester is selected from 1) liquid esters of a C3-C30 carboxylic acid and a C1-C30 alcohol, wherein at least one of the acid or the alcohol is branched or possesses at least one carbon-carbon double bond, or 2) esters of a C7-C30 aromatic acid and a C1-C30 alcohol, wherein the aromatic acid has carboxyl group directly bonded to the aromatic acid's ring;, at least 30% by weight of water relative to the total weight of the composition; and up to 20% by weight of fatty phase relative to the total weight of the composition, with the provisos that the composition is substantially free from fatty acid soap, the composition is free of nonsilicone cationic polymer if the starch is a starch phosphate, and, the carboxylic ester is not isopropyl palmitate or diisopropyl adipate, if the composition comprises a phosphorylated starch derivative, at least one thickener, and less than 3% by weight of surfactant. Second aspect of the present invention provides new cosmetic compositions comprising: a cosmetically acceptable aqueous medium; at least one starch; at least one carboxylic ester in an amount of up to 10% based on the weight of the cosmetic composition wherein the carboxylic ester is selected from 1) liquid esters of a C3-C30 carboxylic acid and a C1-C30 alcohol, wherein at least one of the acid or the alcohol is branched or possesses at least one carbon-carbon double bond, or 2) esters of a C7-C30 aromatic acid and a C1-C30 alcohol, wherein the aromatic acid has carboxyl group directly bonded to the aromatic acid's ring; at least 30% by weight of water relative to the total weight of the composition; and up to 20% by weight of fatty phase relative to the total weight of the composition, with the provisos that the composition is substantially free from fatty acid soap, the composition is free of nonsilicone cationic polymer if the starch is a starch phosphate, and, the carboxylic ester is not isopropyl palmitate or diisopropyl adipate, if the composition comprises at least one thickener, and less than 3% by weight of surfactant. Third aspect of the invention provides for a method of washing or caring for keratinous materials by applying the cosmetic composition defined above to keratinous materials. Fourth aspect of the invention provides for a method of treating or conditioning keratinous materials by applying the cosmetic composition defined above to keratinous materials. detailed-description description="Detailed Description" end="lead"? |
Power efficiency in microprocessors |
A method of reducing the power consumption of microprocessor system is provided, wherein: said microprocessor system comprises a microprocessor (2) and a memory (4) connected by a bus (6); said memory (4) contains a plurality of data values, each represented by a number of bits, for transmission to said microprocessor (2) via the bus (6); and at least some of said data values contain unused bits; and wherein said method includes assigning values to said unused bits in such a way as to reduce the Hamming distance between successive data values by a greater extent than settting all of said unused bits to an arbitrary predetermined value. |
1-21. (Cancelled) 22. A method of reducing the power consumption of a microprocessor system which comprises a microprocessor and a memory connected by at least one bus, said memory containing a plurality of data values, each represented by a number of bits, for transmission to said microprocessor via said at least one bus, and at least some of said data values containing unused bits, said method including assigning values to said unused bits in such a way as to reduce the Hamming distance between successive data values by a greater extent than setting all of said unused bits to an arbitrary predetermined value. 23. A method as claimed in claim 22, which further comprises the steps of: considering each bit of each data value in turn and, if a particular bit of the considered data value is unused, assigning to said particular bit the value of the corresponding bit from an adjacent data value. 24. A method as claimed in claim 23, wherein said adjacent data value is adjacent to said considered data value in said memory. 25. A method as claimed in claim 23, wherein said adjacent data value is adjacent to said considered data value in the sequence in which said data values are read from said memory. 26. A method as claimed in claim 23, wherein said adjacent data value precedes said considered data value. 27. A method as claimed in claim 23, wherein said adjacent data value follows said considered data value. 28. A method as claimed in claim 22, wherein said data values represent instructions to said microprocessor. 29. A method as claimed in claim 28, which further comprises the step of determining whether each instruction is a point of divergence. 30. A method as claimed in claim 29, wherein if said microprocessor employs pipelining, then points of divergence are considered to be the instructions an appropriate distance after branch instructions. 31. A method as claimed in claim 29, wherein for instructions which are points of divergence, assignment of unused bits in the instruction is based on the preceding instruction. 32. A method as claimed in claim 28, which further comprises the step of determining whether each instruction is a point of convergence. 33. A method as claimed in claim 32, wherein for instructions which are points of convergence, assignment of unused bits in the instruction is based on the following instruction. 34. A method as claimed in claim 28, wherein for instructions which have only one possible preceding instruction and one possible following instruction, assignment of unused bits in the instruction is based on either the preceding or the following instruction. 35. A method as claimed in claim 28, wherein in the case of an instruction which is both a point of divergence and a point of convergence, assignment of unused bits in the instruction is based on a consideration of bits in multiple preceding and following instructions. 36. A method as claimed in claim 35, wherein assignment of unused bits in the instruction is based on a consideration of the probabilities of different paths to and from said instruction. 37. A method as claimed in claim 35, wherein assignment of unused bits in the instruction is simply based on an adjacent instruction. 38. A method as claimed in claim 28, wherein if any unused bits remain unassigned after the method has been carried out, then these unused bits are seeded using the corresponding bits from an adjacent instruction. |
Method and system for broadcasting short video sequences to a nomad user |
The invention concerns a method for broadcasting short video sequences to a nomad user. The nomad user is provided with a mobile UMTS terminal (2) connected, via a telecommunication network (6), to a server (3) associated with a database (4). The database (4) comprises short video sequences (5). The method is characterized in that it consists in: identifying the terminal from its identifiers, calculating the terminal display capabilities, taking into account the size of the screen and/or computing capacities and/or image processing means comprised in the terminal, addressing to the server (3) a request for obtaining the video sequences. |
1. Process designed to broadcast information related to everyday life and linked with a gestural practice ergonomically to a wandering user, and at his request; the wandering user having a UMTS mobile terminal connected, via a UMTS standard telecommunications network, to a server associated with a data base; said data base comprising short video sequences illustrating the gestural practice; the process comprising the following steps: the step, for the server, recognizing the UMTS mobile terminal from identifiers of the UMTS mobile terminal, the step, for the server, computing the display capacities of the UMTS mobile terminal, taking into account the size of the screen and/or computing capacities and/or image processing means contained by the UMTS mobile terminal, the step, for the user, of addressing a request to the server with the aim of obtaining the information related to everyday life and linked with a gestural practice; the request being addressed to the server by means of the UMTS mobile terminal, either by entering the data of the request by means of said ordering means, selected from a group consisting of selection means, a pointing means and a keyboard, associated with the UMTS mobile terminal, or by a voice operation, the server comprising voice recognition means to recognize the voice operation of the user; the process additionally comprising the following steps, in response to the request: the step of selecting the short video sequences illustrating said gestural practice in the data base associated with the server as a function of the request and the display capacities of the UMTS terminal; the step of sending the short video sequences from the server to the UMTS terminal via the UMTS standard telecommunications network. 2. Process in accordance with claim 1, the process additionally comprising: the step, for the server, of computing and adapting said short video sequences as a function of the display capacities on the UMTS terminal. 3. Process in accordance with any of claims 1 or 2, the process additionally comprising: the step, for the server, of adapting, in real time, at least one of a sending rate a computing and a selection of the short video sequences to a quantity of information actually received by the UMTS terminal as computed by the server, taking into account performances of the telecommunications network; performances being evaluated, in real time, by a call processor. 4. Process in accordance with any of the claims 1 or 2; the server, from which the information related to everyday life and linked with a gestural practice is broadcast, being operated by a service provider in return for payments; the process additionally comprising the step, for the server, of carrying out the operations of posting the payments according to at least one of the two cases below; (a) payment through an operator of the UMTS standard telecommunications network if the user accesses the server through an operator of the UMTS standard telecommunications network and if the service provider has concluded a contract with the telecommunications operator, the step of carrying out the operations of posting the payments comprises, for the server: the step of informing the user of the price that the telecommunications operator will add to the contractual device connecting the user to the telecommunications operator, the step of sending the short video sequence to the terminal of the user after the consent of the user has been received. (b) direct payment by the user if the user accesses the server through an operator of the UMTS standard telecommunications network and if the service provider has not concluded a contract with the telecommunications operator the step of carrying out the operations of posting the payments comprises, for the server: the step of informing the user of the price that the service provider will invoice to the user, the step of sending the short video sequence to the terminal of the user after the consent of the user has been received. 5. Process in accordance with any of the claims 1 or 2; the process additionally comprising the step of introducing technical and/or business data related to marketable goods and/or services within the short video sequences. 6. Process in accordance with claim 5; the process additionally comprising: the step of offering to the user, during the sending of said short video sequences and/or before or after the sending, the possibility of purchasing the goods or services, such that a business relationship may thus be established between the user and the supplier of the marketable goods and/or services. 7. Process in accordance with claim 6; said process additionally comprising the following steps: the step of informing the user that payments will be due by the user and/or the supplier of the marketable goods and/or services to the service provider, in return for the establishing of a business relationship, the step of posting the payments due by the user and/or the supplier of the marketable goods and/or services to the service provider in return for the establishing of a business relationship. 8. Process in accordance with claim 6; said process additionally comprising the following steps: the step of offering to the user the possibility of refusing the sending of the short video sequences, comprising the establishing of a business relationship between the user and the supplier, the step of sending the short video sequence to the terminal of the user after the consent of the user has been received, comprising the establishing of a business relationship between the user and the supplier. 9. Process in accordance with claim 5; the process being such that the step of introducing technical and/or business data related to goods and/or services within the short video sequences uses at least one of the methods selected from among the following group of methods: (a) the method of superimposing images or a continuous set of images of a promotional or advertising nature in the form of visual and/or audio banners on the short video sequence, (b) the method of inserting one or more sequence in the short video sequence that only contain images or a continuous set of images of a promotional or advertising nature with or without audio comments, (c) the method of showing or demonstrating the use of goods or services of a marketable nature by the images with audio comments or by a continuous set of images with audio comments in the short video sequence, (d) the method of inserting the trademark, logo, a marked product or any distinctive sign of a marketable product and/or service within the short video sequence in a clearly visible and/or audible manner. 10. Process in accordance with claims 1 or 2; the process being such that the duration of the short video sequences is at the most equal to 9 minutes. 11. A system designed to broadcast information related to everyday life and linked with a gestural practice in the form of said short video sequences illustrating the gestural practice to a wandering user, and at his request, in an ergonomic manner; the system comprising: a UMTS mobile terminal used by the user, a server comprising: a call processor a data base; the data base comprising said short video sequences (5) illustrating the gestural practice; the system additionally comprising: a UMTS gateway connecting the server, via a UMTS standard telecommunications network, to the UMTS mobile terminal, so that the server can receive and/or send data to the UMTS mobile terminal; the call processors comprising: identification means operating in real time for recognizing the UMTS mobile terminal from identifiers of the UMTS mobile terminal, computing means for computing the display capacities of the UMTS mobile terminal, taking into account the size of the screen and/or the computing capacities and/or image processing means contained in the UMTS mobile terminal, voice recognition means, the UMTS mobile terminal comprising the ordering means, which can be actuated by the user, to address a request to the server with the aim of obtaining the information related to everyday life and linked with a gestural practice; the ordering means that can be actuated by the user for addressing the request comprising: data entering means, selected from a group including a selection means, a pointing means, a keyboard, voice operation means, the server comprising voice recognition means for recognizing a voice operation; the server additionally comprising: selection means for selecting the short video sequences illustrating the gestural practice in the data base associated with the server as a function of the request and the display capacities of the UMTS terminal, sending means for sending the short video sequences from the server to the UMTS terminal via the UMTS standard communications network. 12. System in accordance with claim 11; the server being composed of a plurality of secondary servers, which are identical, distinct, and connected either to one another or to a central server. 13. System in accordance with any of the claims 11 or 12; the call processor comprising said computing means for computing and adapting the short video sequences as a function of the display capacities on the UMTS terminal. 14. System in accordance with any of the claims 11 or 12; the call processor comprising said computing means for adapting, in real time, the sending rate and/or the computing and/or selection of the short video sequences as a function of the quantity of information received by the UMTS terminal, taking into account the performances of the telecommunications network; the performances being evaluated, in real time, by the call processor. 15. System in accordance with any of the claims 11 or 12; the server, from which the information related to everyday life and linked with a gestural practice is broadcast, being operated by a service provider in return for payments; the server additionally comprising, by its said call processor, said computing means for processing the payments according to at least one of the two cases below; (a) payment through an operator of the UMTS standard telecommunications network if the user accesses the server through an operator of the UMTS standard telecommunications network and if the service provider has concluded a contract with the telecommunications operator, the server additionally comprises: computing means for supplying information, in real time, to the user, including the price that the telecommunications operator will add to the contractual device connecting the user to the telecommunications operator, sending means for sending the short video sequence to the terminal of the user after the consent of the user has been received. b) direct payment by the user if the user accesses the server through an operator of the UMTS standard telecommunications network and if the service provider has not concluded a contract with the telecommunications operator, the server additionally comprises: computing means for supplying information, in real time, to the user, including the price that the service provider will invoice to the user, sending means for sending the short video sequence to the terminal of the user after the consent of the user has been received. 16. System in accordance with any of the claims 11 or 12; the system additionally comprising said image processing means for introducing technical and/or business data related to marketable goods and/or services within the short video sequences. 17. System in accordance with claim 16; the system additionally comprising: interactive data processing means, using the UMTS telecommunications network to offer, via the UMTS mobile terminal, to the user, during the sending of the short video sequences and/or before or after the sending, the possibility of purchasing the goods or services, so that a business relationship may thus be established between the user and the supplier of the marketable goods and/or services. 18. System in accordance with claim 17; the system additionally comprising: data processing means for informing the user, via the UMTS mobile terminal, that the payments will be due by the user and/or the supplier of the marketable goods and/or services to the service provider, in return for the establishing of a business relationship, and computing means for posting the payments due by the user and/or the supplier of the marketable goods and/or services to the service provider in return for establishing the business relationship. 19. System in accordance with any of the claim 17; the system being such that: the UMTS mobile terminal additionally comprising the ordering means that can be actuated by the user for refusing the sending of the short video sequences, comprising the establishing of a business relationship between the user and the supplier, the server additionally comprising the sending means for sending the short video sequence to the terminal of the user after the consent of the user has been received, comprising the establishing of a business relationship between the user and the supplier. 20. System in accordance with any of the claims 17, such that the image processing means for introducing technical and/or business data related to goods and/or services within said short video sequences uses at least one of the means selected from among the following group of means: (a) superimposing means for superimposing images or a continuous set of images of a promotional or advertising nature in the form of visual and/or audio banners on the short video sequence, (b) insertion means for inserting one or more sequence in the short video sequence that only contain images or a continuous set of images of a promotional or advertising nature with or without audio comments, (c) showing means for showing or demonstrating the use of goods or services of a marketable nature by the images with audio comments or by a continuous set of images with audio comments in the short video sequence, (d) insertion means for inserting the trademark, logo, a marked product or any distinctive sign of a marketable product and/or service within the short video sequence in a clearly visible and audible manner. 21. System in accordance with any of the claims 11 or 12, such that the duration of the short video sequences is at the most equal to 9 minutes. 22. A server designed to broadcast information related to everyday life and linked with a gestural practice in the form of said short video sequences illustrating the gestural practice to a wandering user, and at his request, in an ergonomic manner; the wandering user having a UMTS mobile terminal; the server comprising: a call processor, a data base; the data base comprising said short video sequences illustrating the gestural practice; the server being connected, via a UMTS standard telecommunications network, to the UMTS mobile terminal; so that the server can receive and/or send data to the UMTS mobile terminal; the server comprising: identification means for recognizing the UMTS mobile terminal from identifiers of the UMTS mobile terminal, computing means for computing the display capacities of the UMTS mobile terminal, taking into account the size of the screen and/or the computing capacities and/or image processing means contained in the UMTS mobile terminal, voice recognition means, receiving means for receiving a request sent by the user from the UMTS mobile terminal; the aim of the request being to obtain the information related to everyday life and linked with a gestural practice; the request having been formulated by the user by entering data, particularly by a selection means and/or by a pointing means and/or by means of a keyboard associated with the UMTS mobile terminal, and/or by using a voice operation; the server additionally comprising, if the request is formulated in the form of a voice operation, said voice recognition means for recognizing the voice operation; the server additionally comprising: data processing means for processing the request; selection means for selecting the short video sequence illustrating the gestural practice in the data base associated with the server as a function of the request and the display capacities of the UMTS terminal, sending means for sending the short video sequences from the server to the UMTS mobile terminal, via the UMTS standard communications network. 23. Server in accordance with claim 22; the server being composed of a plurality of said secondary servers, which are identical, distinct, and connected either to one another or to a central server. 24. Server in accordance with one of the claims 22 or 23; the call processor comprising said computing means for computing and adapting the short video sequences as a function of the display capacities on the UMTS terminal. 25. Server in accordance with one of the claims 22 or 23; the call processor comprising said computing means for adapting, in real time, the sending rate and/or the computing and/or selection of the short video sequences as a function of the quantity of information received by the UMTS terminal, taking into account the performances of the telecommunications network; the performances being evaluated, in real time, by the call processor. 26. Said server in accordance with any of the claims 22 or 23; the server, from which the information related to everyday life and linked with a gestural practice is broadcast, being operated by a service provider in return for payments; the server additionally comprising said computing means for processing the payments according to at least one of the two cases below: (a) payment through an operator of the UMTS standard telecommunications network if the users accesses the server through an operator of the UMTS standard telecommunications network and if the service provider has concluded a contract with the telecommunications operator, the server additionally comprises: computing means for supplying information, in real time, to the user, including the price that the telecommunications operator will add to the contractual device connecting the users to the telecommunications operator, sending means for sending the short video sequence to the terminal of the user after the consent of the user has been received. (b) direct payment by the user if the user accesses the server through an operator of the UMTS standard telecommunications network and if the service provider has not concluded a contract with the telecommunications operator, the server additionally comprises: computing means for supplying information, in real time, to the user, including the price that the service provider will invoice to the user, sending means for sending the short video sequence to the terminal of the user after the consent of the user has been received. 27. The server in accordance with any of the claims 22 or 23; the server additionally comprising image processing means for introducing technical and/or business data related to marketable goods and/or services within the short video sequences. 28. The server in accordance with claim 27; the server additionally comprising: interactive image means using said UMTS standard telecommunications network to offer, via the UMTS mobile terminal, to the user, during the sending of the short video sequences and/or before or after the sending, the possibility of purchasing the goods or services, so that a business relationship may thus be established between the user and the supplier of the marketable goods and/or services. 29. The server in accordance with claim 28; the server additionally comprising: computing means for informing the user, in real time, via the UMTS terminal, that the payments will be due by the user and/or the supplier of the marketable goods and/or services to the service provider, in return for the establishing of a business relationship, computing means for posting payments due by the user and/or the supplier of the marketable goods and/or services to the service provider in return for establishing the business relationship. 30. The server in accordance with claim 28; the user having refused the sending of the short video sequences, comprising the establishing of a business relationship between the user and the supplier; the server additionally comprising: means for processing the refusal decision, particularly comprising said voice recognition means, sending means for sending the short video sequence to the terminal of the user after the consent of the user has been received, comprising the establishing of a business relationship between the user and the supplier. 31. The server in accordance claim 28, such that the image processing means for introducing technical and/or business data related to goods and/or services within the short video sequences uses at least one of the means selected from among the following group of means: (a) a superimposing means for superimposing images or a continuous set of images of a promotional or advertising nature in the form of visual and/or audio banners on the short video sequence, (b) a insertion means for inserting one or more sequence in the short video sequence that only contain images or a continuous set of images of a promotional or advertising nature with or without audio comments, (c) a showing means for showing or demonstrating the use of goods or services of a marketable nature by the images with audio comments or by a continuous set of images with audio comments in the short video sequence, (d) a insertion means for inserting the trademark, logo, a marked product or any distinctive sign of a marketable product and/or service within the short video sequence in a clearly visible and audible manner. 32. The server in accordance with any of the claims 22 or 23, such that the duration of the short video sequences is at the most equal to 9 minutes. |
Vaccines |
The present invention provides novel adjuvant formulations for use with cancer antigens. The adjuvant comprises a saponin and a immunostimulatory oligonucleotide. |
1. An immunogenic composition comprising a cancer antigen selected from the group: i) an antigen from the MAGE protein family linked to a heterologous fusion partner; ii) prostase antigen linked to a heterologous fusion partner; iii) prostase fragments optionally linked to a heterologous fusion partner; iv) P501S; v) Cripto; vi) Her-2/neu antigen derivative devoid of a substantial portion of the Her-2/neu transmembrane domain, and an adjuvant composition comprising a saponin, together with an immunostimulatory oligonucleotide. 2. A composition as claimed in claim 1 further comprising a lipopolysaccharide. 3. A composition as claimed in claim 1 wherein the saponin is QS21. 4. A composition as claimed in any of claim 2 or 3 wherein the lipopolysaccharide is selected from the group of i Monophosphoryl Lipid A ii 3-0-Deacylated Monophosphoryl Lipid A iii Disphosphoryl Lipid A 5. An immunogenic composition as claimed in any of claims 1 to 4 wherein the immunostimulatory oligonucleotide contains at least two CpG motifs. 6. An immunogenic composition as claimed in any of claims 1 to 5 wherein the immunostimulatory oligonucleotide is selected from the group: SEQ ID No 1 TCC ATG ACG TTC CTG ACG TT (CpG 1826)- SEQ ID No 2 TCT CCC AGC GTG CGC CAT (CpG 1758)- SEQ ID No 3 ACC GAT GAC GTC GCC GGT GAC GGC ACC ACG- SEQ ID No 4 TCG TCG TTT TGT CGT TTT GTC GTT (CpG 2006)- SEQ ID No 5—TCC ATG ACG TTC CTG ATG CT (CpG 1668) 7. A composition as claimed in any of claims 1 to 6 wherein the saponin is formulated to form ISCOMS or liposomes. 8. A composition as claimed in any of claims 1 to 6 wherein the saponin is present in an oil in water emulsion. 9. A composition as claimed in any of claims 1 to 8 comprises substantially all of the extracellular domain of Her 2 neu. 10. A composition as claimed in claim 8 wherein the Her 2 neu molecule is devoid of a functional transmembrane domain. 11. A composition as claimed in claim 1 to 10 which additional comprises the phosphorylation domain of Her 2 neu. 12. A method of treating a patient suffering from or susceptible to, a cancer expressing a Her 2 neu or prostate specific/tumour antigen comprising administering a safe and effective amount of a composition according to any of claims 1 to 11. 13. A method of treating a patient suffering from or susceptible to a cancer expressing any of MAGE, prostase, P501S or Cripto comprising administering a safe and effective amount of a composition according to any of claims 1 to 11. 14. Use of a combination of a saponin an immunostimulatory oligonucleotide and a cancer antigen selected from the group: i) an antigen from the MAGE protein family linked to a heterologous fusion partner; ii) prostase antigen linked to a heterologous fusion partner; iii) prostase fragments optionally linked to a heterologous fusion partner; iv) P501S; v) Cripto; vi) Her-2/neu antigen derivative devoid of a substantial portion of the Her-2/neu transmembrane domain, in the manufacture of a medicament for the treatment or prophylaxis of tumours. 15. A method of manufacture of a composition as claimed in any of claims 1 to 11, comprising admixing a cancer antigen selected from the group: i) an antigen from the MAGE protein family linked to a heterologous fusion partner; ii) prostase antigen linked to a heterologous fusion partner; iii) prostase fragments optionally linked to a heterologous fusion partner; iv) P501S; v) Cripto; vi) Her-2/neu antigen derivative devoid of a substantial portion of the Her-2/neu transmembrane domain, with a saponin and CpG molecule. |
Model selection for cluster data analysis |
A model selection method is provided for choosing the number of clusters, or more generally the parameters of a clustering algorithm. The algorithm is based on comparing the similarity between pairs of clustering runs on sub-samples or other perturbations of the data. High pairwise similarities show that the clustering represents a stable pattern in the data. The method is applicable to any clustering algorithm, and can also detect lack of structure. We show results on artificial and real data using a hierarchical clustering algorithm. |
1. A method for clustering data in a dataset comprising: selecting a plurality of granularity levels k; applying a clustering algorithm to a sub-sample of the dataset so that k clusters are produced; for each k, selecting a plurality of sub-samples of the dataset; selecting a plurality of pairs of sub-samples calculating a similarity between the plurality of pairs; determining a distribution of the similarity between the plurality of pairs; comparing the distributions for all k; and selecting as the optimum granularity level, the k corresponding to the tightest distribution. 2. The method of claim 1, wherein the clustering algorithm is A k-means algorithm. 3. The method of claim 1, wherein the clustering algorithm is hierarchical clustering. 4. The method of claim 1, wherein the step of selecting the highest granularity level comprises selecting a number of clusters for which there is a transition from a distribution that is peaked near 1 to a wide distribution. 5. The method of claim 1, further comprising, after determining the distribution, calculating a cumulative distribution function for each granularity level, wherein the step of selecting the highest granularity level comprises identifying an increase in the area under the cumulative distribution function. 6. The method of claim 1, wherein the data comprises gene expression coefficients. 7. A method for analysis of data in a dataset comprising: selecting a plurality of granularity levels in a clustering algorithm; for each granularity level: inducing a perturbation in the data; selecting a plurality of pairs of perturbations; computing a pairwise similarity for each plurality of pairs; determining a distribution of the pairwise similarity; selecting the highest granularity level having the tightest distribution. 8. The method of claim 7, wherein the step of inducing comprises grouping the data into a plurality of sub-samples. 9. The method of claim 8 wherein the step of grouping comprises applying a k-means clustering algorithm to the data. 10. The method of claim 8 wherein the step of grouping comprises applying a hierarchical clustering algorithm to the data. 11. The method of claim 7, wherein the step of inducing a perturbation comprises initialization of the k-means algorithm. 12. The method of claim 7, wherein the step of inducing a perturbation comprises adding random noise to the data. 13. The method of claim 7, wherein the step of selecting the highest granularity level comprises selecting a number of clusters for which there is a transition from a distribution that is peaked near 1 to a wide distribution. 14. The method of claim 7, further comprising, after determining the distribution, calculating a cumulative distribution function for each granularity level, wherein the step of selecting the highest granularity level comprises identifying an increase in the area under the cumulative distribution function. 15. The method of claim 7, wherein the data comprises gene expression coefficients. 16. A method for clustering data comprising a plurality of structured patterns, the method comprising: (a) selecting a clustering algorithm based on a dissimilarity measure between pairs of structured patterns; (b) randomly assigning class labels to the structured patterns; (c) defining a plurality of cluster centers by averaging structured patterns within each labeled class; (d) measuring dissimilarity between each structured pattern and its corresponding cluster center by measuring a residual of a fit of one structured pattern onto another structured pattern; (e) reassigning structured patterns to the labeled class with the most similar cluster center; and (f) repeating steps (c) through (e) until assignment of structured patterns to the labeled classes remains constant. 17. The method of claim 16, wherein step (d) comprises using a fit that is invariant with respect to affine transformations. 18. The method of claim 17, wherein the affine transformations comprise a combination of translation, scaling and rotation. 19. The method of claim 16, further comprising calculating an average structured pattern, wherein the residual is an average residual of the fit of each structured pattern to the average structured pattern. 20. The method of claim 16, wherein step (d) comprises measuring a Euclidean distance and a residual of a fit of one structured pattern onto another structured pattern. 21. The method of claim 16, further comprising, after step (c), clustering the cluster centers. 22. The method of claim 16, wherein the clustering algorithm is a k-means algorithm. 23. The method of claim 16, wherein the structured patterns are temporal profiles. 24. The method of claim 23, wherein the temporal profiles are gene expression profiles. 25. A method for clustering patterns in a dataset comprising: selecting a plurality of granularity levels k; selecting a clustering algorithm adapted for producing a number of cluster centers equal to k and for assigning patterns to clusters corresponding to the cluster centers; for each granularity level k: (a) inducing perturbations in the dataset to generate a modified dataset; (b) applying the clustering algorithm to the at least one modified dataset to produce k clusters under each of the perturbations; (c) creating a new dataset comprising the cluster centers identified in step (b); (d) applying the clustering algorithm to the new dataset using the same value of k clusters; (e) determining the stability of the clusterings at each granularity level k by measuring dissimilarity between data in the new dataset and the cluster center for the cluster into which the data was assigned; measuring fit of the data to the cluster centers for all k; and selecting as the optimum granularity level the k corresponding to the best fit. 26. The method of claim 25, wherein the perturbations comprise a combination of one or more of sub-sampling the dataset, changing initialization of the clustering algorithm, and adding noise to the dataset. 27. The method of claim 25, wherein the dataset comprises gene expression profiles. |
<SOH> BACKGROUND OF THE INVENTION <EOH>Knowledge discovery is the most desirable end product of data collection. Recent advancements in database technology have lead to an explosive growth in systems and methods for generating, collecting and storing vast amounts of data. While database technology enables efficient collection and storage of large data sets, the challenge of facilitating human comprehension of the information in this data is growing ever more difficult With many existing techniques the problem has become unapproachable. Thus, there remains a need for a new generation of automated knowledge discovery tools. As a specific example, the Human Genome Project has completed sequencing of the human genome. The complete sequence contains a staggering amount of data, with approximately 31,500 genes in the whole genome. The amount of data relevant to the genome must then be multiplied when considering comparative and other analyses that are needed in order to make use of the sequence data. As an illustration, human chromosome 20 alone comprises nearly 60 million base pairs. Several disease-causing genes have been mapped to chromosome 20 including various autoimmune diseases, certain neurological diseases, type 2 diabetes, several forms of cancer, and more, such that considerable information can be associated with this sequence alone. One of the more recent advances in determining the functioning parameters of biological systems is the analysis of correlation of genomic information with protein functioning to elucidate the relationship between gene expression, protein function and interaction, and disease states or progression. Proteomics is the study of the group of proteins encoded and regulated by a genome. Genomic activation or expression does not always mean direct changes in protein production levels or activity. Alternative processing of mRNA or post transcriptional or post-translational regulatory mechanisms may cause the activity of one gene to result in multiple proteins, all of which are slightly different with different migration patterns and biological activities. The human proteome is believed to be 50 to 100 times larger than the human genome. Currently, there are no methods, systems or devices for adequately analyzing the data generated by such biological investigations into the genome and proteome. Clustering is a widely used approach for exploratory data analysis. Clustering analysis is unsupervised learning—it is done without suggestion from an external supervisor; classes and training examples are not given a priori. The objective of clustering is to group data points into “meaningful” subsets. There is no agreed upon definition of the clustering problem, and various definitions appear in the literature. For example, clustering has been defined as a search for some “natural” or “inherent” grouping of the data. However, most clustering algorithms do not address this problem. The vast majority of clustering algorithms produce as their output either a dendogram or a partition into a number of clusters, where the number of clusters is either the input, or there is some other parameter(s) that controls the number of clusters. In either case, a model selection technique is required in order to choose the model parameter, or in the case of hierarchical algorithms, to determine which level of the dendogram represents the “inherent” structure of the data. A few examples of applications of clustering include (1) analysis of microarray data, where co-expressed genes are found, and the assumption is that co-expression might be a sign of co-regulation; (2) in medical datasets (gene expression data, clinical data etc.), where patients are divided into categories; (3) in any set or set of measurements to detect trends or artifacts in the measurement protocol; and (4) in information retrieval to partition text according to categories. Most clustering algorithms either produce a hierarchical partitioning of the data into smaller and smaller clusters, or produces a partition of a dataset into a number of clusters that depend on some input parameter (the number of clusters or some other parameter(s)). The question remains, however, of how to set the input parameter, or how to determine which level of the tree representation of the data to look at: Clustering algorithms are unsophisticated in that they provide no insight into the level of granularity at which the “meaningful” clusters might be found. Occasionally, there may be prior knowledge about the domain that facilitates making such a choice. However, even in such cases, a method for determining the granularity at which to look at the data is required. This is seen as the problem of finding the optimal number of clusters in the data, relative to some clustering algorithm. E. Levine and E. Domany in “Resampling Method for Unsupervised Estimation of Cluster Validity”, Neural Comp. 13, 2573-2593 (2001), assign a figure of merit to a clustering solution according to its similarity to clusterings of subsamples of the data. The “temperature” parameter of their clustering algorithm is selected according to a maximum of the similarity measure. However, in real data, such a maximum does not often occur. Other model selection techniques have difficulty detecting the absence of structure in the data, i.e., that there is a single cluster. Further, many of algorithms make assumptions as to cluster shape, and do not perform well on real data, where the cluster shape is generally not known. Accordingly, other methods for clustering are needed. The present invention is directed to such a method. |
<SOH> SUMMARY OF THE INVENTION <EOH>In an exemplary embodiment, a system and method are provided for analysis of data by grouping the input data points into meaningful subsets of data. The exemplary system comprises a storage device for storing at least one data set, and a processor for executing the clustering algorithm. In the preferred embodiments, the clustering algorithm is a k-means or hierarchical clustering algorithm. In the method of the present invention, a “good granularity level”, i.e., an optimal number of clusters, is defined as one at which a clustering solution is stable with respect to some perturbation of the data, such as noise or sub-sampling. For each level of granularity, the algorithm chooses a number of pairs of sub-samples or other perturbations, clusters each subsample with the chosen level of granularity, then computes a similarity between pairs of clustering solutions. For each level of granularity, the distribution of the similarity between pairs of clustering solutions is computed, then the highest level of granularity for which highly similar solutions are obtained under perturbation is chosen. According to the present invention, the probability distribution of the similarity measure is evaluated in order to find the “true” number of clusters based on a similarity measure between clustering solutions. A dot product between pairs of clustering solutions is normalized to provide a similarity measure. Other similarity measures proposed in the literature can also be expressed in terms of this dot product. In one embodiment, the inventive method provides means for extraction of information from gene expression profiles, in particular, extraction of the most relevant clusters of temporal expression profiles from tens of thousands of measured profiles. In one variation of the present embodiment, the clustering algorithm is the k-means algorithm. Other embodiments include all pairwise clustering methods (e.g., hierarchical clustering) and support vector clustering (i.e., a support vector machine (SVM)). In one variation, the fit involves affine transformations such as translation, rotation, and scale. Other transformations could be included, such as elastic transformations. In the case of k-means, the algorithm is applied in a hierarchical manner by sub-sampling the data and clustering the sub-samples. The resulting cluster centers for all the runs are then clustered again. The resulting cluster centers are considered to be the most significant profiles. To facilitate the clustering task, a ranking of the genes is first performed according to a given quality criterion combining saliency (significant difference in expression in the profile), smoothness, and reliability (low noise level). Other criteria for ranking include the local density of examples. |
Multi-video receiving method and apparatus |
A method and apparatus is disclosed for receiving a plurality of video signals using a single video signal transmitted using a point-to-multipoint connection; the plurality of video signals originate from various locations of an event. Information received using a reception unit comprises at least one of the plurality of video signals, at least one of the plurality of sound track signals related to the at least one of the plurality of video signals, data transmitted using the vertical blanking interval (VBI) of the single video signal and graphics. |
1. A method for providing a plurality of video programs to a plurality of video program receivers having a first resolution using a single frequency band enabling transmission of a video program having a second resolution substantially higher than the first resolution, the method comprising the steps of: receiving a plurality of video programs from a plurality of video program sources, the plurality of video programs having a resolution substantially equal to the second resolution; formatting each of the plurality of video programs received from the plurality of video program sources to have a resolution substantially equal to the first resolution; inserting each of the formatted video programs at a specific location in a main video signal having a resolution substantially equal to the second resolution; transmitting the main video signal to each of the plurality of video program receivers. 2. The method as claimed in claim 1, wherein the main video signal comprises a data signal provided by a data signal source. 3. The method as claimed in claim 1, wherein four video programs are received, the main video signal being a NTSC signal. 4. The method as claimed in claim 1, further comprising the step of receiving a plurality of sound tracks from a plurality of sound track sources, each of the plurality of sound tracks being attached to one of the plurality of video programs, the method further comprising the step of formatting each of the plurality of sound tracks in order to have a sound resolution compatible with a sound resolution of the video program receivers, the sound resolution of the video program receivers being substantially lower than the main video signal sound resolution, the method further comprising the step of inserting the formatted plurality of sound tracks in the main video signal. 5. The method as claimed in claims 1-4, further comprising the step of encoding the main video signal prior said transmitting. 6. The method as claimed in claim 5, wherein the encoding is performed by switching at least two lines in the main video signal. 7. The method as claimed in claim 1, wherein the video program sources are live video signals of specific locations of a common event. 8. The method as claimed in claim 2, wherein the video program sources are live video signals of specific locations of a common event. 9. The method as claimed in claim 8, wherein the common event is a live event. 10. The method as claimed in claim 8, wherein the data signal source provides data related to said event or to a participant of said event. 11. An apparatus for displaying at least one of a plurality of video program signals inserted in a main video signal, the at least one of a plurality of video program signals having a first resolution, the main signal having a second resolution substantially higher than the first resolution, the apparatus comprising: a receiving unit receiving the main video signal; a user interface for enabling a user to select at least one of the plurality of video programs contained in said main video signal for a display, the user interface providing a command signal representative of the selected at least one of the plurality of video programs to display; a display screen, receiving the selected video signal for display; a processing unit receiving the main video signal and selecting at least one part of the main video signal provided by the receiving unit according to said command signal provided by the user interface, the selected one of the plurality of video programs to display being displayed on said display screen. 12. The apparatus as claimed in claim 11, wherein the receiving unit is receiving a plurality of main video signals, the user interface further enabling the user to select one of the plurality of main video signals. 13. The apparatus as claimed in claim 11, further comprising an audio unit, receiving an audio signal from said receiving unit, wherein the main video signal comprises a plurality of sound tracks signals, each of the plurality of sound tracks signals being related to one of the plurality of video program signals. 14. The apparatus as claimed in claim 11, wherein the main video signal is encoded using a code, the apparatus further comprising a configuration storing unit storing said code, the processing unit further decoding the received main video signal according to said code stored in said storing unit. 15. The apparatus as claimed in claim 11, further comprising a remote control interface unit, the remote control interface unit being connected to said processing unit and receiving a remote control signal from a remote computer. 16. The apparatus as claimed in claim 11, wherein said first resolution is substantially 360×240. 17. The apparatus as claimed in claim 11, wherein said second resolution is 720×480. 18. The apparatus as claimed in claim 15, wherein said remote control interface unit is a serial compatible port unit. 19. The apparatus as claimed in claim 11, wherein said display screen is a LCD active matrix screen. 20. An apparatus for broadcasting at least one of a plurality of video program signals inserted in a main video signal to a plurality of receiving units, each receiving unit having a first resolution, the main signal having a second resolution substantially higher than the first resolution, the apparatus comprising: a formatting unit receiving the at least one of a plurality of video programs signals, the formatting unit formatting the at least one of a plurality of video program signals to have a resolution substantially equal to a resolution of a receiving unit, the resolution of the receiving unit being substantially lower than the resolution of the main video signal; a combining unit, receiving the formatted at least one of a plurality of video signals and incorporating each of the formatted at least one of a plurality of video signals into a specific location in the main video signal; a transmitter, receiving the main video signal and transmitting the main video signal to the plurality of receiving units. 21. The apparatus as claimed in claim 20, wherein the formatting unit further comprises a sound track formatting unit, receiving a plurality of sound tracks signals from a plurality of sound tracks sources having a first sound resolution, each of the plurality of sound track sources being related to one of the plurality of video programs, and providing a plurality of converted sound track sources having a second sound resolution substantially lower that the first sound resolution, the combining unit further receiving said converted sound tracks and incorporating said converted sound tracks into said main video signal. 22. The apparatus as claimed in claim 20 , further comprising an encoding unit, the encoding unit receiving main video signal and providing an encoded main video signal to said transmitter. 23. A method for transmitting a video program to a plurality of video program receivers having a first resolution using a single frequency band enabling transmission of a video program having a second resolution substantially higher than the first resolution, the method comprising the steps of: receiving said video program from a video program source, the video program having a resolution substantially equal to the second resolution; formatting the video program received from the video program source to have a resolution substantially equal to the first resolution; inserting the formatted video program at a specific location in a main video signal having a resolution substantially equal to the second resolution; encoding the main video signal using an encoding scheme; transmitting the main video signal to each of the plurality of video program receivers. |
<SOH> BACKGROUND OF THE INVENTION <EOH>Assisting to a live event is usually an enjoyable experience as all our senses are overwhelmed by various sensations. The assisting is therefore more enjoyable than a remote assisting via a television program related to said event. Unfortunately, it is usually difficult to have more than one view of the event when assisting to said event. This is particularly true during Formula I Grand Prix competitions, where a viewer is usually seated at a particular point of the circuit. Usually in that case, the viewer cannot have access to other parts of the circuit unless a large screen is available for instance. This may avoid the viewer to enjoy an action that is taking place at another location of the circuit unavailable to him. Various solutions have been implemented in order to enable the viewer at the live event to access more information about the event. For instance, in some major car racing events, such as CART/NASCAR, radio scanners are available. Such radio scanners enable the live event viewer to scan and listen to conversations between a pilot and his crew. Unfortunately the device lacks excitement and entertainment because it only offers sound, making it difficult for the user to easily understand who they are listening to and being potentially more disruptive than enhancing. Mini portable television sets have been developed and are already available on the market. Via such mini portable television sets, the live event user can watch the race to the extent that it is broadcast, but, in most cases, the live events are broadcast on cable TV and are therefore inaccessible to these devices. These mini portable television sets have therefore limited applications and do not offer the excitement or any added value of the event that would motivate the users to widely use it. Wireless handled devices based on web technology have also been developed. These devices run on PDA and are linked to the web. Such devices provide VIP guests and general audience live timing and scoring, radio feeds and background info on team cars, car drivers, golf players, etc. They integrate rich multimedia and interactive interfaces. Unfortunately, these devices lack with many drawbacks. A first drawback is the fact that the technology is usually implemented using a point-to-point connection, such point-to-point connection does not allow a massive use of the device at a live event as an important frequency bandwidth would be necessary to serve an important number of users. Such devices have a limited effectiveness when delivery video content due to the limited bandwidth used. Moreover, data compression schemes are mandatory in order to cope with limited bandwidth. It is difficult, in these conditions, to have a real time transmission of video data streams. These devices are also very expensive due to the fact that they are based on an expensive hardware architecture. There is a need for a method and apparatus to overcome the abovementioned drawbacks. |
<SOH> SUMMARY OF TE INVENTION <EOH>It is an object of the invention to provide a method for broadcasting more than one video program and data to a plurality of reception units; It is another object of the invention to provide an apparatus for broadcasting more than one video program and data to a plurality of reception units using a point-to-multipoint connection; It is another object of the invention to provide a method for receiving more than one video program and data transmitted using a wireless point-to-multipoint connection; It is another object of the invention to provide an apparatus for receiving more than one video program and data transmitted using a wireless point-to-multipoint connection; According to the above objects, from a broad aspect, the present invention provides a method for providing a plurality of video programs to a plurality of video program receivers having a first resolution using a single frequency band enabling transmission of a video program having a second resolution substantially higher than the first resolution, the method comprising the steps of receiving a plurality of video programs from a plurality of video program sources, the plurality of video programs having a resolution substantially equal to the second resolution; formatting each of the plurality of video programs received from the plurality of video program sources to have a resolution substantially equal to the first resolution; inserting each of the formatted video programs at a specific location in a main video signal having a resolution substantially equal to the second resolution and transmitting the main video signal to each of the plurality of video program receivers. According to another broad aspect of the invention, there is provided an apparatus for broadcasting at least one of a plurality of video program signals inserted in a main video signal to a plurality of receiving units, each receiving unit having a first resolution, the main signal having a second resolution substantially higher than the first resolution, the apparatus comprising a formatting unit receiving the at least one of a plurality of video programs signals, the formatting unit formatting the at least one of a plurality of video program signals to have a resolution substantially equal to a resolution of a receiving unit, the resolution of the receiving unit being substantially lower than the resolution of the main video signal, a combining unit, receiving the formatted at least one of a plurality of video signals and incorporating each of the formatted at least one of a plurality of video signals into a specific location in the main video signal and a transmitter, receiving the main video signal and transmitting the main video signal to the plurality of receiving units. According to another broad aspect of the invention, there is provided an apparatus for displaying at least one of a plurality of video program signals inserted in a main video signal, the at least one of a plurality of video program signals having a first resolution, the main signal having a second resolution substantially higher than the first resolution, the apparatus comprising a receiving unit receiving the main video signal, a user interface for enabling a user to select at least one of the plurality of video programs contained in said main video signal for a display, the user interface providing a command signal representative of the selected at least one of the plurality of video programs to display, a display screen, receiving the selected video signal for display and a processing unit receiving the main video signal and selecting at least one part of the main video signal provided by the receiving unit according to said command signal provided by the user interface, the selected one of the plurality of video programs to display being displayed on said display screen. |
Plant for the continous processing and packing of meat products |
It comprises an injection station (10); a maceration station (20), including a massaging rotating drum (22) and several drawn quiescent tanks (24); and a packaging station (30). Such stations are linked by an accumulation and loading unit (40) to the drum (22) located between the said injection station (10) and the maceration station (20); a reloading unit (50) located between the station (20) and the unit (40); and a transferring unit (60) to a feeding hopper (62) of the said packaging station (30) including an automatic cleaning unit (70) for the tanks (24). A control centre coordinates the operations steps of the stations and units for keeping a non-stop operation, providing a time for cleaning each station, unit or part thereof during such cycle. |
1. Plant for treating and packaging meat product in a non-stop operation comprising: a station of brine injection (10) to the meat products to be treated; a maceration station (20) for the injected meat products including at least a rotating massaging drum (22) for the injected meat product and a plurality of quiescent tanks (24) for the massaged meat products connected to drawing means to make it moves forwards step-to-step along a closed path (26) around such rotating drum (22); and a packaging station (30) for the treated meat products such stations being coupled to each other for a non-stop operation, linked by a unit for accumulating and loading (40) the injected meat product in the rotating drum (22), located between the outlet of such injection station (10) and the inlet of the said maceration station (20), comprising: at least a first and a second hoppers (42, 44); a distributing device (46) for distributing the meat product coming from the injection station (10) alternatively to the said first and second hoppers (42,44); a reloading unit (50) located between the said maceration station (20) and the said accumulating and loading unit (40) comprising means for newly transferring the massaged-settled meat product coming from the said quiescent tanks (24) to the said second hopper (44) to be reloaded in the said rotating drum (22); and a unit for transferring (60) the treated meat product to a feeding hopper (62) of the said packaging station (30), in addition it includes a unit for cleaning (70) the quiescent tanks (24) at a point of the path (26) after the unit for transferring (60) at least a computer control centre being provided for coordinating the steps of such stations and units operation so that at any moment of a plant working cycle at least one of such stations is operating, a time being provided for cleaning each station, unit or part thereof during the said cycle, keeping the plant non-stop operation characterized in that it comprises an inlet hopper (12) for accumulating lots of meat products to be treated, the said inlet hopper (12) being provided with first means for detecting the weight of the said lots and means (13) for feeding the meat products of each weighed lots to an injection machine (14) of the said injection station (10), means being incorporated at the said computer control centre to determine the amount of brine to be injected to each lot depending on its weight detected. 2. Plant, according to the claim 1, characterized in that it comprises a conveyor belt (11) for transferring the meat product from the outlet of the said injection machine (14) to the distributing device (46) of the accumulating and loading unit (40) and a tenderizing machine (15) associated to the said conveyor belt (11) to superficially cut the injected meat product before it is accumulated in the first and second hoppers (42, 44) and subsequently loaded in the rotating drum (22), the said conveyor belt (11) jointly with the said tenderizing machine (15) are mounted on a moving truck (16) displaceable between a working position and a cleaning position. 3. Plant according to claim 2, characterized in that the said moving truck (16) comprises, at one end, feet (36) provided with wheels and, at the other end, a sliding support (18) which may be moved retained on and be guided by at least one guide (19) horizontally fixed on a supporting structure (45) of the said first and second hoppers (42, 44), the said guide (19) has a first end corresponding to the working position and a second end (19a) sidewards protruding beyond the said supporting structure (45) corresponding to the cleaning position. 4. Plant according to claim 3, characterized in that, in the said working position, a first end (11a) of the conveyor belt (11) is located under the said outlet of the injection machine (14) and a second end (11b) of the conveyor belt (11) is located on an inlet of the said tenderizing machine (15), which is fixed to the moving truck (16) and an outlet from which it is located on the said distributing device (46) while at the said cleaning position, as well the conveyor belt (11) as the injection machine (14) are far away other components and structures and are fully accessible. 5. Plant, according to claim 1, characterized in that each of the said first and second hoppers (42, 44) of the accumulating and loading unit (40) have associated second weight detecting means (41) and means incorporated to the said computer control centre for controlling the said distributing device (46) for distributing the meat product between the first and the second hoppers (42, 44) depending on a weight sought for each lot of injected meat product to be loaded subsequently in the said rotating drum (22). 6. Plant for treating and packaging meat product in a non-stop operation comprising: a station of brine injection (10) to the meat product to be treated; a maceration station (20) for the injected meat product including: at least a rotating massaging drum (22) for the injected meat product provided with a loading/unloading mouth (23) and means for tilting the said drum (22) in order to unload it through the said loading/unloading mouth (23); a plurality of quiescent tanks (24) for the massaged meat product connected to drawing means to make it moves forwards step-to-step along a closed path (26) around such rotating drum (22); and a packaging station (30) for the treated meat products such stations are coupled to each other for a non-stop operation, linked by a unit for accumulating and loading (40) the injected meat product in the rotating drum (22), located between the outlet of such injection station (10) and the inlet of the said maceration station (20), comprising: at least a first and a second hoppers (42, 44); a distributing device (46) for distributing the meat product coming from the injection station (10) alternatively to the said first and second hoppers (42, 44); and transferring means for selectively transferring the load from the first and second hoppers (42, 44) in the rotating drum (22) of the maceration station (20), a reloading unit (50) located between the said maceration station (20) and the said accumulating and loading unit (40) comprising means for newly transferring the massaged-settled meat product coming from the said quiescent tanks (24) to the said second hopper (44) to be reloaded in the said rotating drum (22); and a unit for transferring (60) the treated meat product to a feeding hopper (62) of the said packaging station (30), located between a given point of the said path (26) of the maceration station (20) and the packaging station (30), including in addition a unit for cleaning (70) the quiescent tanks (24) at a point of the path (26) after the unit for transferring (60) at least a computer control centre being provided for coordinating the steps of such stations and units operation so that at any moment of a plant working cycle at least one of such stations is operating, a time being provided for cleaning each station, unit or part thereof during the said cycle, keeping the plant non-stop operation characterized in that it comprises two alternative automatic operation tops (21, 28) for such loading/unloading mouth (23) of such rotating drum (22), such tops (21, 28) having different characteristics for performing different functions depending on the steps in the working cycle: A first top or loading top (21) connected to a hose (25) directing the meat product coming from the said transfer means to the accumulating and loading unit (40) and mounted on a first moving arm (27) driven to switch over the said loading top (21) between an idle position, withdrawn from the said loading/unloading mouth (23) and a working position coupled to the loading/unloading mouth (23), when the drum (22) is stopped, to proceed to load by sucking due to a depression created by a vacuum pump within the drum (22) through a duct located at a blind axial end of the drum (22), opposed to the loading/unloading mouth (23); and a second top or massaging top (28) is mounted on a support (95) fixed on the free end of a second moving arm (29) driven to switch over the said second top (28) between an idle position, withdrawn from the said loading/unloading mouth (23), and a working position coupled to the loading/unloading mouth (23) either when the drum is stopped or rotating during a massaging sub-cycle, the said support (95) includes means to allow the massaging top (28) rotates around a shaft (86) integral with it and to absorb small circular translations of the said shaft (86) when rotating jointly with the drum (22), due to possible misalignments between the shaft (86) and the actual spin axis of the drum (22). 7. Plant, according to claim 6, characterized in that the outlet of the first and the second hoppers (42, 44) of the accumulating and loading unit (40) are located respective flow valves (42a, 44a), driven by respective fluid dynamic cylinders (47), from the said flow valves (42a, 44a) are departing respective hoses (49a, 49b) which are joined in a collector which offers a single common outlet mouth (49) connected to the said hose (25), means having being provided incorporated in the said computer control centre to selectively drive the said flow valves (42a, 44a) and controlling the said first moving arm (27) and vacuum pump to load the contents of either the first or the second hoppers (42, 44) in the rotating drum (22). 8. Plant according to claim 7 characterized in that a duct for conducting cold and/or hot water and a hose for conducting detergent, supported on the said first moving arm (27) are connected to respective inlets of water and detergent (84, 85) of the said first top (21) for automatically cleaning the inside of the drum (22). 9. Plant according to claim 7, characterized in that the said first moving arm (27) comprises a structure of stiff bars (90) which form an arcuate shape along which remains delimited and protected an internal space through which is passing and supported a hose (25), such structure of stiff bars (90) is hinged by a first end (90a) distal from the said first loading top (21) to a supporting structure (45) of the said first and second hoppers (42, 44), and linked by a medium area (90b) with the fluid dynamic cylinder rod (91) the head of which is linked to such supporting structure (45), the said fluid dynamic cylinder (91) drives such first arm (27) to carry out such switching over between the said working and idle positions of the first loading top (21). 10. Plant according to claim 6, characterized in that the said shaft (86) integral with the massaging top (28) outwardly protrudes from it and is substantially aligned with the spin axis of the drum (22) when the massaging top (28) is in such working position, such shaft (86) being supported and guided by at least a bearing (87) housed in a bearing-holder (88) mounted on elastic bearing means (89) built in the said support (95) of the second moving arm (29), so that when the massaging top (28) rotates jointly with the drum (22) the said shaft (86) can rotate and make the said small circular translations with respect to the said second arm (28) against the strength of the said elastic means (89). 11. Plant according to claim 10, characterized in that the said elastic means comprise a plurality of helical springs (89) star-shaped radially arranged in housings of the said support (95) of the said free end of the second arm (29), the external ends of the helical springs (89) being supported on adjustable depth bottoms (96) of the said housings and their internal ends being supported against the said bearing-holder (88), the strength of such springs (89) being adjustable by adjusting the depth of the related bottom (96) of the housing. 12. Plant, according to claim 10, characterized in that the said second moving arm (29) comprises at its ends distal from the massaging top (28) a hinge (29a) with respect to a tiltable supporting structure (92) of the said rotating drum (22) and a fluid dynamic cylinder (94) has its rod linked to a cranked handle (93) integral with the hinge pin (29a) and a head linked to the said tiltable structure (92) the fluid dynamic cylinder (94) of which drives such second arm (29) to carry out the said switch over between the said working and idle positions of the second massaging top (21). 13. Plant for treating and packaging meat product in a non-stop operation of the kind comprising: a station of brine injection (10) to the meat products to be treated; a maceration station (20) for the injected meat product including: at least a rotating massaging drum (22) for the injected meat product; a plurality of quiescent tanks (24) for the massaged meat products coming from the said rotating drum (22); drawing means to make the quiescent tanks (24) move forwards step-to-step along a closed path (26) around such rotating drum (22), which is at least one, with a stop under the loading/unloading mouth (23) for receiving meat product from the said drum (22) and keep it settling during a predetermined time, the tanks (24) which can be unhooked off such drawing means at least in some predetermined stop positions; and a packaging station (30) for the treated meat products such stations are coupled to each other for a non-stop operation, linked by a unit for accumulating and loading (40) the injected meat product in the rotating drum (22), located between the outlet of such injection station (10) and the inlet of the said maceration station (20), comprising: at least a first and a second hoppers (42, 44); and transferring means for selectively transferring the load of the first and second hoppers (42, 44) to the rotating drum (22) of the maceration station (20), a reloading unit (50) located between the said maceration station (20) and the said accumulating and loading unit (40) comprising means for newly transferring the massaged-settled meat product coming from the said quiescent tanks (24) to the said second hopper (44) to be reloaded in the said rotating drum (22); and a unit for transferring (60) the treated meat product to a feeding hopper (62) of the said packaging station (30), located between a given point of the said path (26) of the maceration station (20) and the packaging station (30), including in addition a unit for cleaning (70) the quiescent tanks (24) at a point of the path (26) after the unit for transferring (60) at least a computer control centre being provided for coordinating the steps of such stations and units operation so that at any moment of a plant working cycle at least one of such stations is operating, a time being provided for cleaning each station, unit or part thereof during the said cycle, keeping the plant non-stop operation characterized in that such quiescent tanks (24) are provided with wheels (100) and can rotate on a track (103) arranged around the said rotating drum (22), each quiescent tank (24) is provided in addition with fastening means for releasably fasten a related drawing truck (101) guided along a rail (102) fixed on the floor, such rail (102) defining such closed cycle path (26) along such track (103) all such drawing trucks (101) being linked to each other by means of hinged bars (105) forming an endless flexible transmitting element along the said rail (102) driving, coupling and guiding means (106, 107, 108, 109) being provided for successively coupling each of such drawing trucks (101) when it is located in a predetermined position and moving it, drawing the rest of the drawing trucks (101) together with all the quiescent tanks (24) one step until the following drawing truck (101) occupies such predetermined stop position and then disconnect such drawing truck (101) and newly coming backwards to the predetermined position. 14. Plant, according to claim 13, characterized in that the said rail (102) comprises a flat faced handrail fixed on the floor with its cross sectional bigger size upright and the drawing truck (101) comprises at least supporting wheels (117) which rotates on the top face of the said handrail (102) and guiding wheels (118, 119), facing each other by pairs, with a wheel of each pair rotating on opposite sides of the handrail (102), one of the wheels (119) of each pair being mounted on a eccentric shaft (120) to facilitate its mounting adjustment. 15. Plant, according to claim 13, characterized in that the said driving, coupling and guiding means (106, 107, 108, 109) act on a length of the said path (26) in which the rail (102) defines a circumference arc (102a) with the beginning at the said predetermined position and comprise an arm (106), angularly moving, hinged at one end with respect to a vertical shaft (106a) located at the centre of the said circumference arc (102a) and guided by the opposite end (106b) with respect to a curved guide (107) parallel to the circumference arc (102a), a first fluid dynamic cylinder (108), having a long run, with its head hinged at a fixed point (108a) with respect to the floor and at the end of its rod linked to the said opposite end (106b) of the arm (106) and a second fluid dynamic cylinder (109), having a short run, fixed on the said opposite end (106b) of the arm (106), such second fluid dynamic cylinder (109) comprises, fixed at the end of its rod, a coupling element (110) which can be connected/disconnected in a complementary anchoring element (111) integral to each drawing truck (101) due to the said fluid dynamic cylinder rod (109) extending/retracting. 16. Plant, according to claim 15, characterized in that, at another point of the path (26) a locking element (116) is fixed to the end of the rod of another fluid dynamic cylinder (121) having a short run, which is in a fixed position and is driven for coupling the said locking element (116) with the said anchoring element (111) of a drawing truck (101) stopped in front of it in order to lock the assembly of quiescent tanks (24) during the periods in which they are stopped. 17. Plant, according to claim 13, characterized in that the said fastening means for releasably fastening a quiescent tank (24) on a related drawing truck (101) comprise a pair of upright stubs (112) integral with outwardly protruding platforms (113) in each drawing truck (101), such stubs (112) are socketed in holes (114) located in plates (115) horizontally protruding from a side of each quiescent tank (24) at a suitable height, means (55, 56, 59, 61) being provided for lifting the said quiescent tanks (24) sufficiently to disconnect the said holes (114) from the said stubs (112) and withdraw the quiescent tanks (24) from the said path (26) in the said predetermined stop positions. 18. Plant for treating and packaging meat product in a non-stop operation comprising: a station of brine injection (10) to the meat product to be treated; a maceration station (20) for the injected meat products including at least a rotating massaging drum (22) for the injected meat product; a plurality of quiescent tanks (24) for the massaged meat product coming from such rotating drum (22); drawing means to make such quiescent tanks (24) move forwards step-to-step along a closed path (26) around such rotating drum (22) which is at least one, with a stop under the loading/unloading mouth (23) for receiving meat product from the said drum (22) and keep it settling during a predetermined time, the tanks (24) which can be hooked off such drawing means at least in some predetermined stop positions; and a packaging station (30) for the treated meat products, such stations are coupled to each other for a non-stop operation, linked by a unit for accumulating and loading (40) the injected meat product in the rotating drum (22), located between the outlet of such injection station (10) and the inlet of the said maceration station (20), comprising at least a first and a second hoppers (42, 44); and transferring means for selectively transferring the load of the first and second hoppers (42, 44) to the rotating drum (22) of the maceration station (20), a reloading unit (50) located between the said maceration station (20) and the said accumulating and loading unit (40) comprising means for newly transferring the massaged-settled meat product coming from the said quiescent tanks (24) to the said second hopper (44) to be reloaded in the said rotating drum (22); and a unit for transferring (60) the treated meat product to a feeding hopper (62) of the said packaging station (30), located between a given point of the said path (26) of the maceration station (20) and the packaging station (30), including in addition a unit for cleaning (70) the quiescent tanks (24) at a point of the path (26) after the transfer unit (60) and where the said accumulating and loading (40) and transferring (60) units include lifting-tippling apparatuses (52,64) provided with means for taking one of the quiescent tanks (24), filled, from a related stop position from the path (26), lifting and tippling it to transfer its contents to the said second hopper (44) of the accumulating and loading unit (40) or to the said hopper (62) of the transfer unit (60), respectively, and bring it back, empty, to the related stop position of the path (26), at least one computer control centre being arranged for coordinating the operation steps of the said stations and units so that at any moment of a working cycle of the plant at least one of the stations is operating, a time being provided for cleaning each station, unit or part thereof during the said cycle, keeping the non-stop operation of the plant, characterized in that, each of the said lifting-tippling apparatuses (52,64) comprises: a structure (51), having a suitable height, open by one of its side faces leaning on the path (26), such structure (51) incorporating an unloading ramp (53) at the top end of another of its side faces; means (55,56,59,61) for lifting one of such quiescent tanks (24) sufficiently to disconnect holes (114) located in plates (115) horizontally protruding from a side of the quiescent tank (24) from upright stubs (112) integral with platforms (113) associated to a corresponding drawing truck (101) of the quiescent tanks along the path (26) and transfer such quiescent tank (24) hooked off the path (26) to the inside of the structure bottom (51); and means for fastening and uprightly lifting the quiescent tank (24) inside the said structure (51) and tippling it on the said unloading ramp (53) at the top end of the structure (51). 19. Plant, according to claim 18, characterized in that such means for lifting, disconnecting and transferring such quiescent tanks (24) from the path (26) to the inside of the structure bottom (51) comprise: rails (54) horizontally extending from inside the structure bottom (51) through the said open side face until crossing the said track (103) of the path (26) such rails (54) have interruptions at the passing areas for the said wheels (100) of the quiescent tanks (24); a displacing truck (55) driven by a fluid dynamic cylinder (56) having a long run to horizontally move on the said rails (54) between a first position to a stop position of the quiescent tanks (24) on the path (26) and a second position inside the structure (51), such displacing truck (55) provided with at least three wheels (58) at each side arranged for rolling on the rails (54) so that when one of the said wheels (58) is located on one of such interruptions of the rails (54) at least two other wheels (58) are supported on the said rails (54); an uprightly moving platform (59) mounted on the said displacing truck (55) and connected to the ends of the rods of fluid dynamic cylinders (61) uprightly fastened on the displacing truck (55) and driven for lifting the said moving platform (59) together with a quiescent tank (24) located on it, up to the said sufficient height, the said means (55, 56, 59, 61) being also capable of the opposite operation, that is to say, transferring a quiescent tank (24) emptied, at a slightly lifted position, from the fastening means inside the structure (51) bottom to the path (26), and going down the quiescent tank (24) for hooking it to the related drawing truck (101). 20. Plant, according to claim 18, characterized in that the said fastening and uprightly lifting and tippling means of the quiescent tank (24) comprise: a lifting truck (63) located inside the said structure (51) and uprightly guided along guides (68) fixed on the said side face of the structure (51) ending in the said unloading ramp (53), the said lifting truck (63) is going up and down on the said guides (68) driven by a chain mechanism (71) and a fluid dynamic cylinder (73); a tippler (65) for a quiescent tank (24), such tippler being linked to a top part of the said lifting truck (63) by means of a substantially horizontal hinge (66) and linked by a point relatively far away from the said hinge (66) to the end of the fluid dynamic cylinder rod (67) the head of which is linked to a lower part of the lifting truck (63), when driving the said fluid dynamic cylinder (67) this causes that the quiescent tank (24) is tippled fastened on the said tippler (65) around the hinge (66) to empty its contents on the unloading ramp (53). 21. Plant, according to claim 20, characterized in that the said tippler (65) comprises a top part (72) having guides horizontally arranged y adapted for receiving frames (69) provided at the top part of the quiescent tanks (24) when a quiescent tank (24) is introduced inside the structure (51) by the said displacing truck (55) and a side supporting wall (74) which is extending downwards from the said top part (72) and which cooperates with such guides (57) for supporting the quiescent tank (24) when it is tippled about the hinge (66). 22. Plant, according to claim 18, characterized in that the said side face of the structure (51) ended by the said unloading ramp (53) and along which the guides (68) are fixed is facing the said open face of the structure (51) and perpendicular to the said rails (54), therefore the said hinge (66) with respect to which the quiescent tanks (24) are tippled is substantially parallel or tangent to the path (26) and is useful for the unit (60) transferring to the feeding hopper (62) in the cases that the availability of space allows to place such hopper (62) far away the path (26). 23. Plant, according to claim 19, characterized in that the said face of the structure (51) ending by the said unloading ramp (53) and along which the guides (68) are fixed is a face contiguous to the said open face of the structure (51) and parallel to the said rails (54), therefore such hinge (66) with respect to which tippling the quiescent tanks (24) is carried out is substantially perpendicular to the path (26) and is useful for the reloading unit (50), because of the relative positions of the second hopper (44) and rotating drum (22) required, or from the transferring unit (60) to the feeding hopper (62) in the cases that a scarce availability of space requires that the said hopper (62) is placed very close to the path (26). 24. Plant, according to claim 22 or 23, characterized that the said hopper (62) of the transferring unit (60) comprises a single outlet (31) connected to a distributing device from which are starting two or more hoses (33) connected to as many other packaging machines (32, 34), which have sucking means for sucking the treated meat product from the said hopper (62) according to its rating. 25. Plant according to claim 18, characterized in that the said cleaning unit comprises an automatic cleaning cabinet (77) arranged adjacent to a track (103) of the path (26) through which are moving the quiescent tanks (24) and a pivoting arm (76) hinged to the bottom of the said cabinet (77) such arm (76) having a lifting end with a concealable bottom frame on a portion of the said track (103) and a side supporting wall close to the said bottom frame, the said pivoting arm 76 being capable to rotate with respect to its hinge driven by a fluid dynamic cylinder for taking a quiescent tank (24) stopped on the said bottom frame and lift it unhooking it from its related drawing truck (101), on a circular path until introducing it laying on the said side supporting wall inside the automatic cleaning cabinet (77) where it is cleaned and thereafter returning the clean quiescent tank to the path (26) newly hooking it to the drawing truck (101). |
<SOH> TECHNICAL BACKGROUND <EOH>The application for an international patent PCT/ES 00/00061 of this applicant discloses a plant and a process for a non-stop treatment and packaging of the meat product which sets the main lines of such kind of plant depending on stages or steps of a specific process to be implemented in a plant having a non-stop operation. The process of the said application for a patent PCT/ES 00/00061 essentially comprises the operations of injecting brine to meat products; macerating such injected meat product submitting it to one or more massaging actions alternating with as many quiescent periods; and packaging the treated meat products and characterized in that such operations are carried out in a plant controlled by a centralized control in a chained and automated way, alternatively on different lots of meat products so that at any moment at least two of such lots of meat products are being simultaneously submitted to one of such operations, times for cleaning the different units and stations of the plant having being provided while other units or stations are operating keeping the plant non-stop operation. To implement such method, the plant of the application for a patent PCT/ES 00/00061 comprises a station for brine injection to the meat products to be treated, a maceration station for the injected meat products including at least a rotating drum for massaging the injected meat product and a plurality of tanks for the massaged meat products settling connected to drawing means to make them move forwards step by step along a closed path around such rotating drum; and a packaging station for the treated meat product. Such stations are coupled to each other for a non-stop operation, linked by a unit for accumulating and loading the injected meat product in the rotating drum, located between the outlet of such injection station and the inlet of the said maceration station, the said accumulating and loading unit comprises at least a first and a second hoppers; a distributing device for distributing the meat product coming from the injection station alternatively to the said first and second hoppers; a reloading unit located between the said maceration station and the said accumulating and loading unit comprising means for newly transferring the massaged-settled meat product coming from the said quiescent tanks to the said second hopper to be reloaded in the said rotating drum; and a unit for transferring the treated meat product to a feeding hopper ( 62 ) of the said packaging station. The plant in addition includes a unit for cleaning the quiescent tanks located at a point of the path after the said unit for transferring the meat product to the packaging station. The plant is controlled by the said computer control centre, which coordinates the steps of such stations and units operation so that at any moment of a plant working cycle at least one of such stations is operating, a time being provided for cleaning each station, unit or part thereof during the said cycle, keeping the plant non-stop operation. In the said plant, the injected meat product is accumulated by lots alternatively in such first and second hoppers of the accumulating and loading unit. The accumulated lot in one of the hoppers is loaded in the rotating drum and submitted to a massaging operation in it while the other hopper is being loaded with another lot of meat products. The lot massaged within the drum is transferred thereafter to one or several of such quiescent tanks which rotate around the drum. The drum, once it has been emptied can be loaded with a new lot of meat product coming from one of the hoppers while the massaged lot sustains a period at rest in related tanks. Preferably, the plant includes a reloading unit with means for transferring a lot of settled meat product from its related quiescent tanks to the said first and second hoppers, and from it newly in the rotating drum for sustaining a new massaging and settling cycle, and so on. The macerated meat product, at the end of the programmed massaging and settling cycled, is transferred by means of the said transfer unit to the hopper feeding the packaging station while new lots are sustaining prior operations. Thus, the plant has a non-stop operation and it is taken profit of the times when some of the stations, units or parts thereof are idle to hand or automatically wash them. |
Chloromethylation of thiophene |
The process according to the invention relates to the preparation of 2-chloromethyl-thiophene of the formula (I). During this process thiophene is chloromethylated in the presence of one or more compounds containing keto group and optionally it is transformed into the compound of the formula (II). Compounds of formula (I) and (II) are intermediates of several pharmaceutically active ingredients. |
1. A process for the preparation of a compound of the formula (I): by chloromethylation of thiophene in the presence of one or more compounds containing a keto-group. 2. A process according to claim 1 wherein the chloromethylation is carried out in a dialkyl-ketone type solvent. 3. A process according to claim 2 wherein the chloromethylation is carried out in acetone or methyl-ethyl-ketone or methyl-isobutyl- ketone. 4. A process according to claim 1 wherein the chloromethylation is carried out between −15° C. and +20° C. 5. A process according to claim 1 wherein the chloromethylation is carried out by using aqueous concentrated hydrochloric acid, gaseous hydrogen chloride and paraformaldehyde. 6. A process according to claim 5 wherein the dry hydrogen chloride gas is introduced into the reaction mixture or it is used after absorption in a compound containing a keto-group. 7. A process according to claim 5 wherein the molar ratio of thiophene, aqueous hydrochloric acid, gaseous hydrogen chloride and paraformaldehyde is 1.0:(1.0-1.3):(0.75-1.0):1.0. 8. A process according to claim 1 wherein 1 to 3 volumes of the compound containing a keto-group are used per volume of thiophene. 9. A process according to claim 5 wherein an inorganic salt is dissolved in the aqueous hydrogen chloride solution. 10. A process according to claim 1 wherein the compound of the formula (I) is transformed further into a compound of formula (II). 11. A process according to claim 10 wherein the compound of the formula (I) is transformed further without isolation into a compound of formula (II). 12. A process according to claim 9 wherein the compound of formula (I) is reacted with aqueous alkali cyanide optionally in the presence of a phase-transfer catalyst to give a compound of formula (II). 13-14. (canceled) 15. A process according to claim 8 wherein 2.0 to 2.6 volumes of the compound containing a keto group are used per volume of thiophene. 16. A process according to claim 9 wherein the inorganic salt is calcium chloride. |
Biosensor |
In order to provide a biosensor with high accuracy and excellent response where plasma obtained by filtration of blood rapidly arrives at an electrode system, in a biosensor comprising: an insulating base plate; an electrode system having a working electrode and a counter electrode which are provided on the base plate; a reaction layer including at least oxidoreductase and an electron mediator; a sample solution supply pathway which includes the electrode system and the reaction layer and has an inlet and an air aperture; a sample solution supply part for introducing a sample solution, which is in position apart from the sample solution supply pathway; and a first filter which is disposed between the sample solution supply pathway and the sample solution supply part for filtering the sample solution, where the filtrate filtered with the first filter is supplied into the sample solution supply pathway due to capillary action, the direction in which the sample solution passes through the first filter and the direction in which the filtrate passes through the sample solution supply pathway are made cross at right angles. |
1. A biosensor comprising: an insulating base plate; an electrode system having a working electrode and a counter electrode which are provided on said base plate; a reaction layer including at least oxidoreductase and an electron mediator; a sample solution supply pathway which includes said electrode system and said reaction layer and has an inlet and an air aperture; a sample solution supply part for introducing a sample solution, which is in position apart from said sample solution supply pathway; and a first filter which is disposed between said sample solution supply pathway and said sample solution supply part for filtering said sample solution, where a filtrate filtered with said first filter is supplied into said sample solution supply pathway due to capillary action, characterized in that the direction in which said sample solution passes through said first filter and the direction in which said filtrate passes through said sample solution supply pathway cross at right angles. 2. The biosensor in accordance with claim 1, comprising at least one space surrounding the surface of said first filter in the region from the side of said sample solution dropping part to the inlet side of said sample solution supply pathway, of said first filter. 3. The biosensor in accordance with claim 1 or 2, wherein in said first filter, the cross sectional area of said sample solution supply part side is larger than the cross sectional area of the inlet side of said sample solution supply pathway. 4. The biosensor in accordance with any of claims 1 to 3, wherein the cross sectional area of said sample solution supply part side of said first filter is larger than the cross sectional area of said sample solution supply pathway side of said first filter. 5. The biosensor in accordance with any of claims 1 to 4, wherein said first filter is constituted by either a glass fiber or a cellulose fiber. 6. The biosensor in accordance with any of claims 1 to 5, wherein said first filter is not in contact with said electrode system. 7. The biosensor in accordance with any of claims 1 to 6, wherein at least part of said first filter is in contact with said insulating base plate. 8. The biosensor in accordance with any of claims 1 to 7, wherein said first filter is coated with any of polyvinyl alcohol, ethyl cellulose, hydroxypropyl cellulose, carboxymethyl cellulose, polyvinyl pyrrolidone, gelatin, agarose, polyacrylic acid and the salts thereof, starch and the derivatives thereof, polymers of maleic anhydride and the salts thereof, polyacrylamide, methacrylate resin, and poly-2-hydroxyethyl methacrylate. 9. The biosensor in accordance with any of claims 1 to 8, wherein said reaction layer includes a reagent system for detecting total cholesterol. 10. The biosensor in accordance with any of claims 1 to 9, wherein said first filter is constituted by a membrane filter with a uniform pore size in the form of a membrane. 11. The biosensor in accordance with claim 10, wherein a hydrophilic layer is provided between said first filter and said base plate. 12. The biosensor in accordance with any of claims 1 to 11, further comprising a second filter between said first filter and said sample solution supply pathway. 13. The biosensor in accordance with claim 12, wherein the mean pore size of said first filter is smaller than the mean pore size of said second filter. 14. The biosensor in accordance with claim 12 or 13, wherein said second filter is a depth filter. 15. The biosensor in accordance with any of claims 12 to 14, wherein said first filter is in contact with said second filter. 16. The biosensor in accordance with any of claims 12 to 15, wherein said second filter is in contact with the inlet of said sample solution supply pathway. 17. The biosensor in accordance with any of claims 12 to 16, wherein said second filter is in not in contact with said electrode system. 18. The biosensor in accordance with any of claims 12 to 17, wherein said electrode system does not exist in the lower part of the vertical direction of said first filter and said second filter. 19. The biosensor in accordance with any of claims 12 to 18, wherein in said second filter, the cross sectional area of said sample solution supply part side is larger than the cross sectional area of said sample solution supply pathway in the direction vertical to the direction in which said sample solution flows. 20. The biosensor in accordance with any of claims 12 to 19, wherein said first filter and/or said second filter contain a reagent for suppressing a reaction between said oxidoreductase and cholesterol contained in any of high density lipoprotein, low density lipoprotein and very low density lipoprotein in said sample solution. |
<SOH> TECHNICAL FIELD <EOH>The present invention relates to a biosensor capable of carrying out rapid, highly-sensitive, simple determination of a specific component in a sample to be detected such as blood, serum and plasma, especially a biosensor capable of measuring glucose, total cholesterol and the like. |
<SOH> BRIEF DESCRIPTION OF DRAWINGS <EOH>FIG. 1 is an exploded perspective view of a biosensor in accordance with one embodiment of the present invention. FIG. 2 is a combined perspective view of the biosensor in FIG. 1 . FIG. 3 is a sectional view of the main part taken on the line X-X of FIG. 2 , with a reaction layer and the like omitted. FIG. 4 is a sectional view of the main part taken on the line X-X of FIG. 2 , with the reaction layer shown specifically. FIG. 5 is an exploded perspective view of a biosensor in accordance with one embodiment of the present invention. FIG. 6 is a combined perspective view of the biosensor in FIG. 5 . FIG. 7 is a sectional view of the main part taken on the line Y-Y of FIG. 6 , with a reaction layer and the like omitted. FIG. 8 is a sectional view of the main part taken on the line Y-Y of FIG. 6 , with the reaction layer shown specifically. FIG. 9 is a schematic sectional view of a filter device for explaining the mechanism of separating blood. FIG. 10 is a vertical sectional view of a conventional biosensor. FIG. 11 is an exploded perspective view of another conventional biosensor. FIG. 12 is a vertical sectional view of the biosensor shown in FIG. 11 . FIG. 13 is a sectional view of the main part specifically showing a first filter portion of a biosensor in accordance with one embodiment of the present invention. FIG. 14 is a sectional view of the main part specifically showing a first filter portion of a biosensor in accordance with another embodiment of the present invention. FIG. 15 is a sectional view of the main part specifically showing a first filter portion of a biosensor in accordance with still another embodiment of the present invention. FIG. 16 is a graph showing a response characteristic of a biosensor in Example 1. FIG. 17 is a graph showing a response characteristic of a biosensor in Example 2. FIG. 18 is an exploded perspective view of a biosensor in accordance with one embodiment of the present invention. FIG. 19 is a combined perspective view of the biosensor in FIG. 18 . FIG. 20 is a vertical sectional view of the biosensor taken on the line X′-X′ shown in FIG. 19 , with a reaction layer and the like omitted. FIG. 21 is a vertical sectional view of the biosensor taken on the line X′-X′ shown in FIG. 19 , with the reaction layer shown specifically. FIG. 22 is a graph showing the relationship between the total cholesterol concentration in the sample solution and the current response value in Example 1 of the present invention. FIG. 23 is a graph showing the relationship between the glucose concentration in the sample solution and the current response value in Example 2 of the present invention. FIG. 24 is an exploded perspective view of a biosensor in accordance with one embodiment of the present invention. FIG. 25 is a combined perspective view of the biosensor in FIG. 24 . FIG. 26 is a vertical sectional view of the biosensor taken on the line X″-X″ shown in FIG. 25 , with a reaction layer, an electrode system and the like omitted. FIG. 27 is a vertical sectional view of the biosensor taken on the line X″-X″ shown in FIG. 25 , with the reaction layer, the electrode system and the like shown specifically. FIG. 28 is a graph showing the response characteristic of the biosensor with respect to the total cholesterol in Example 5 of the present invention. detailed-description description="Detailed Description" end="lead"? |
Circuit board with at least one electronic component |
A circuit board having, between the circuit board and a component arranged thereon, an electrical and mechanical connection of high mechanical-load-bearing ability. The circuit board includes at least one internally situated conductor path, a first insulating layer arranged on a first surface of the circuit board, a second insulating layer arranged on a second surface of the circuit board, a first contact location at which the conductor path is accessible, a second contact location, at which the conductor path is accessible through a bore passing completely through the circuit board, and an electronic component arranged on the first surface. The component has a first contact surface, which is connected with the first contact location by solder or electrically conductive adhesive, and a second contact surface which is connected with the second contact location by solder or adhesive. |
1-7. (canceled). 8. A circuit board, having a first surface, a second surface and a bore, comprising: at least one internally situated conductor path; a first insulating layer arranged on said first surface of the circuit board; a second insulating layer arranged on said second surface of the circuit board; a first contact location at which said conductor path is accessible; a second contact location, at which said conductor path is accessible through said bore passing completely through the circuit board; and an electronic component arranged on said first surface, which exhibits a first contact surface, which is connected with said first contact location by one of: solder and electrically conductive adhesive, and which exhibits a second contact surface, which is connected with said second contact location by one of: solder and adhesive. 9. The circuit board as defined in claim 8, wherein: said conductor path is accessible at said first contact location through a cavity in said first insulating layer. 10. The circuit board as defined in claim 8, wherein: said conductor path is accessible at said first contact location through said bore. 11. The circuit board as defined in claim 8, wherein: said electronic component is a piezoelectric element, which has at least one flushly applied electrode; and said contact surfaces are portions of said flushly applied electrode. 12. The circuit board as defined in claim 8, wherein: said first and second contact surfaces electrically form a unit. 13. A circuit board having a first surface, a second surface and a bore, comprising: two mutually separated, mutually parallel, internally situated conductor paths; a first insulating layer arranged on said first surface of the circuit board; a second insulating layer arranged on said second surface of the circuit board; a first contact location at which said conductor path nearest said first surface is accessible; a second contact location, at which said conductor paths are accessible by said bore passing completely through the circuit board; and an electronic component arranged on said first surface, which exhibits a first contact surface, which is connected with said first contact location by one of: solder and electrically conductive adhesive, and which exhibits a second contact surface, which is connected with said second contact location by one of: solder and adhesive. 14. The circuit board as defined in claim 13, wherein: said bore has a metallizing in the region of said two conductor paths. 15. The circuit board as defined in claim 13, wherein: said conductor path is accessible at said first contact location through a cavity in said first insulating layer. 16. The circuit board as defined in claim 13, wherein: said conductor path is accessible at said first contact location through said bore. 17. The circuit board as defined in claim 13, wherein: said electronic component is a piezoelectric element, which has at least one flushly applied electrode; and said contact surfaces are portions of said flushly applied electrode. 18. The circuit board as defined in claim 13, wherein: said first and second contact surfaces electrically form a unit. |
Grinding wheel, intermediate product and method for producing a grnding wheel of this type |
A grinding wheel for the grinding of curved surface portions (0) consists basically of a carrying body (2, 12) and an abrasive (3, 13, 23) applied to the carrying body. The carrying body (2, 12) has a circumferential surface (4), of which the section relative to a radial plane (R) has a curvature. The abrasive (3, 13, 23) is arranged on the carrying body (2, 12), at least in the region of the circumferential surface (4). The abrasive thereby likewise has, in section, relative to the radial plane (R), a curvature which corresponds essentially to the curvature of the circumferential surface (4). |
1. A grinding wheel for grinding curved surface portions comprising a carrying body and an abrasive applied to the carrying body, wherein the carrying body has a circumferential surface which has, in section in a radial plane, at least partially a convex curvature, and wherein the abrasive is arranged on the carrying body, at least in the region of the circumferential surface, so that the abrasive has, in section, relative to the radial plane R, a curvature which corresponds approximately to the curvature of the circumferential surface. 2. A grinding wheel of claim 1, wherein the carrying body is designed as a ring. 3. A grinding wheel of claim 1, wherein the crying body is designed as a disk. 4. A grinding wheel of claim 1, wherein the abrasive is clamped on the carrying body by means of a clamping device. 5. A grinding wheel of claim 4, wherein the clamping device is provided with a holding means for fastening the grinding wheel to a grinding machine. 6. A grinding wheel of claim 1, wherein the abrasive is glued to the carrying body. 7. A grinding wheel of claim 1, wherein the abrasive consists of segments which are arranged on the carrying body preferably so as to overlap in the circumferential direction. 8. A grinding wheel of claim 7, wherein the segments are of almond-shaped design. 9. A grinding wheel of claim 2, wherein the abrasive is designed as a belt which is wound in coils on the ring preferably so as to overlap, as seen in the circumferential direction. 10. A grinding wheel of claim 7, wherein the overlap is designed in such a way that the distance of the front end of the segments respectively the coils, in the direction of rotation, from the axis of rotation is shorter than the distance of the rear end, in the direction of rotation, from the axis of rotation. 11. A grinding wheel of claim 1, wherein the abrasive is designed as a belt which, as seen in the circumferential direction, is applied to the carrying body at least on an outer circumferential line of the circumferential surface. 12. A grinding wheel of claim 11, wherein the belt i is provided along its edges with indentations or cutouts 13. A grinding wheel of claim 1, wherein the circumferential surface has a radius of curvature of 3 mm to 8 mm. 14. A grinding wheel of claim 1, wherein the carrier consists of glass-fiber-reinforced plastic. 15. An intermediate product for the production of a grinding wheel of claim 7, wherein the segments are fastened with an inner end to the carrying body and wherein the outer end of the segments projects beyond the outer, circumferential line of the carrying body. 16. A method of making a grinding wheel of claim 7, comprising steps of providing an intermediate product comprising abrasive segments arranged on a carrying body so as to overlap in a circumferential direction, the segments having an outer end fastened to the carrying body and an outer end projecting beyond an outer circumferential line of the carrying body, bending of the outer ends of the segments around the curved circumferential portion and fastening of the outer ends to the carrying body. |
Film-forming cosmetic composition |
The invention concerns a cosmetic composition comprising, in an aqueous medium, a film-forming polymer, an aqueous wax micro-dispersion and an aromatic acid ester, liquid at room temperature and water soluble. The invention also concerns a method for cosmetic make-up or non-therapeutic care of keratinous materials, in particular the skin, comprising application of keratinous materials of said composition. The composition can easily be applied on keratinous materials and forms a glossy and non-sticky film. |
1-37. (canceled) 38. A composition comprising, in an aqueous medium, at least one film-forming polymer, at least one aqueous microdispersion of wax, and at least one water-soluble aromatic acid ester that is liquid at room temperature. 39. The composition according to claim 38, wherein the at least one wax microdispersion comprises wax particles with a mean size of less than 1 μm. 40. The composition according to claim 39, wherein the at least one wax microdispersion comprises wax particles with a mean size of less than 0.5 μm. 41. The composition according to claim 38, wherein the at least one wax microdispersion comprises wax with a melting point ranging from 30° C. to 120° C. 42. The composition according to claim 38, wherein the at least one wax microdispersion comprises wax with a hardness ranging from 0.05 MPa to 15 MPa. 43. The composition according to claim 38, wherein the at least one wax microdispersion comprises wax chosen from beeswax, lanolin wax, Chinese insect waxes, rice wax, carnauba wax, candelilla wax, ouricurry wax, esparto grass wax, cork fibre wax, sugarcane wax, Japan wax, sumach wax, montan wax, microcrystalline waxes, paraffins, ozokerite, polyethylene waxes, the waxes obtained by Fisher-Tropsch synthesis; waxy copolymers and esters thereof; the waxes obtained by catalytic hydrogenation of animal or plant oils comprising linear or branched C8-C32 fatty chains; hydrogenated jojoba oil, hydrogenated sunflower oil, hydrogenated castor oil, hydrogenated coconut oil, hydrogenated lanolin oil; silicone waxes; and mixtures thereof. 44. The composition according to claim 38, wherein the at least one wax dispersion is present in a wax solids content ranging from 0.1% to 50% by weight, relative to the total weight of the composition. 45. The composition according to claim 44, wherein the at least one wax dispersion is present in a wax solids content ranging from 0.5% to 30% by weight, relative to the total weight of the composition. 46. The composition according to claim 45, wherein the at least one wax dispersion is present in a wax solids content ranging from 1% to 20% by weight, relative to the total weight of the composition. 47. The composition according to claim 38, wherein the at least one wax dispersion further comprises at least one additional ingredient chosen from oily and/or pasty fatty additives and from liposoluble additive/active agents. 48. The composition according to claim 38, further comprising at least one surfactant. 49. The composition according to claim 38, wherein that the at least one film-forming polymer is chosen from synthetic free-radical polymers, synthetic polycondensates, polymers of natural origin, and mixtures thereof. 50. The composition according to claim 49, wherein the at least one film-forming polymer is chosen from vinyl polymers resulting from the polymerization of monomers chosen from α,β-ethylenic unsaturated carboxylic acids, esters of said acids, amides of said acids, vinyl esters, and styrene monomers. 51. The composition according to claim 49, wherein the at least one film-forming polymer is chosen from polyurethanes, polyesters, polyesteramides, polyamides, epoxyester resins and polyureas. 52. The composition according to claim 49, wherein the at least one film-forming polymer is chosen from shellac resin, sandarac gum, dammar resins, elemi gums, copal resins, water-insoluble cellulose polymers, and mixtures thereof. 53. The composition according to claim 38, wherein the at least one film-forming polymer is in the form of solid particles dispersed in the aqueous phase. 54. The composition according to claim 38, wherein the at least one film-forming polymer is present in a solids content ranging from 0.1% to 60% by weight, relative to the total weight of the composition. 55. The composition according to claim 54, wherein the at least one film-forming polymer is present in a solids content ranging from 0.5% to 40% by weight, relative to the total weight of the composition. 56. The composition according to claim 55, wherein the at least one film-forming polymer is present in a solids content ranging from 1% to 30% by weight, relative to the total weight of the composition. 57. The composition according to claim 38, wherein the at least one water-soluble aromatic acid ester results from the esterification with an aromatic acid of at least one hydroxyl group of a hydroxylated compound chosen from dimethicone copolyols, polyethylene glycol/polypropylene glycol block polymers and polyoxyalkylenated methylglucosides. 58. The composition according to claim 57, wherein the aromatic acid is chosen from benzoic acid, phenylacetic acid, cinnamic acid, 3-phenylpropanoic acid, salicylic acid, terephthalic acid, trimellitic acid and pyromellitic acid. 59. The composition according to claim 58, wherein the aromatic acid is benzoic acid. 60. The composition according to claim 57, wherein the aromatic acid is a dimethicone copolyol benzoate. 61. The composition according to claim 57, wherein the polyoxyalkylenated methylglucoside is chosen from oxyethylenated methylglucoside and oxypropylenated methylglucoside. 62. The composition according to claim 38, wherein the at least one water-soluble aromatic acid ester is chosen from oxyethylenated methylglucoside benzoate and oxypropylenated methylglucoside benzoate. 63. The composition according to claim 62, wherein the at least one water-soluble aromatic acid ester is an oxyethylenated methylglucoside benzoate of formula (I): wherein: R1, R2, R3 and R4 are each individually the group and the sum w+x+y+z ranges from 10 to 20. 64. The composition according to claim 62, wherein the at least one water-soluble aromatic acid ester is an oxypropylenated methylglucoside benzoate of formula (II): wherein: R′1, R′2, R′3 and R′4 are each individually and the sum of w+x+y+z ranges from 10 to 20. 65. The composition according to claim 57, wherein the aromatic acid ester results from the esterification of an aromatic acid with a polyethylene glycol/polypropylene glycol block polymer. 66. The composition according to claim 65, wherein the polyethylene glycol/polypropylene glycol block polymer is chosen from polyethylene glycol/polypropylene glycol/polyethylene glycol and polypropylene glycol/polyethylene glycol/polypropylene glycol triblock polycondensates. 67. The composition according to claim 65, wherein the at least one water-soluble aromatic acid ester is a benzoate of polyethylene glycol/polypropylene glycol block copolymer. 68. The composition according to claim 67, wherein the at least one water-soluble aromatic acid ester corresponds to formula (III): R5—CO—O—(—CH2—CH2—O)x—(—CH2—CH(CH3)—O)y—(CH2—CH2—O)x—O—CO—R′5 (III) wherein: R5 and R′5, are chosen from hydrogen atoms and phenyl radicals, with the proviso that at least one of the radicals R5 and R′5 is a phenyl radical, x and y, independently of each other, are each a number ranging from 2 to 100. 69. The composition according to claim 68, wherein x and y, independently of each other, are each a number ranging from 2 to 30. 70. The composition according to claim 67, wherein the aromatic acid ester corresponds to formula (IV): R5—CO—O—(—CH(CH3)—CH2—O)x—(—CH2—CH2—O)y—(CH2CH(CH3)—O)x—O—CO—R′5 (IV) wherein: R5 and R′5 are chosen from hydrogen atoms and phenyl radicals, with the proviso that at least one of the radicals R5 and R′5 is a phenyl radical, x and y, independently of each other, are each a number ranging from 2 to 100. 71. The composition according to claim 70, wherein x and y, independently of each other, are each a number ranging from 2 to 30. 72. The composition according to claim 38, wherein the at least one water-soluble aromatic acid ester is present in the composition in an amount ranging from 0.1% to 20% by weight, relative to the total weight of the composition. 73. The composition according to claim 72, wherein the at least one water-soluble aromatic acid ester is present in the composition in an amount ranging from 1% to 15% by weight, relative to the total weight of the composition. 74. The composition according to claim 73, wherein the at least one water-soluble aromatic acid ester is present in the composition in an amount ranging from 5% to 15% by weight, relative to the total weight of the composition. 75. The composition according to claim 38, wherein the at least one film-forming polymer and the at least one aromatic acid ester are present in a weight ratio of film-forming polymer/aromatic acid ester ranging from 0.1 to 3. 76. The composition according to claim 75, wherein the at least one film-forming polymer and the at least one aromatic acid ester are present in a weight ratio of film-forming polymer/aromatic acid ester ranging from 0.5 to 2.5. 77. The composition according to claim 38, further comprising at least one additive chosen from thickeners, plasticizers, coalescers, fillers, dyestuffs, waxes, surfactants, preserving agents, oils and fragrances. 78. The composition according to claim 38, wherein the composition is a cosmetic composition. 79. The composition according to claim 78, wherein the cosmetic composition is in the form of an eyeliner, an eyeshadow, a body makeup product, a lip product, a mascara, a nail varnish, a foundation, an eyebrow product, a haircare product, or a skincare product. 80. A cosmetic process for cosmetically treating a keratin material, comprising applying to the keratin materials a composition comprising, in an aqueous medium, at least one film-forming polymer, at least one aqueous microdispersion of wax, and at least one water-soluble aromatic acid ester that is liquid at room temperature. 81. The process according to claim 80, wherein the keratin material is the skin. 82. A process for obtaining a shiny and/or non-sticky film deposited on a keratin material comprising applying to the keratin material a composition comprising, in an aqueous medium, at least one film-forming polymer, at least one aqueous microdispersion of wax, and at least one water-soluble aromatic acid ester that is liquid at room temperature. 83. A cosmetic composition comprising, in an aqueous medium, at least one film-forming polymer, at least one aqueous microdispersion of wax, and at least one water-soluble aromatic acid ester that is liquid at room temperature, wherein the at least one film-forming polymer, at least one aqueous microdispersion of wax, and at least one water-soluble aromatic acid ester that is liquid at room temperature are present in the composition in a combined effective amount such that the composition applies and/or spreads easily onto a keratin material. |
Glasses and fixing device |
Spectacles comprise a bridge connecting two lenses, and side pieces mounted on the lenses for carrying spectacle bows, the lenses being connected to the side pieces and to the bridge by an attachment means (1). The invention is characterized in that at least one attachment means (1) comprises a U-shaped wire loop (2) which is inserted into a bore in a lens and is secured by means of a plug (3) in such manner that the wire is urged into positive engagement with axially extending grooves in a wall of the bore. An attachment means (1) for spectacles, with which spectacle lenses are connected to spectacles side pieces and to a spectacles bridge, is characterized in that at least one attachment means (1) comprises a U-shaped wire loop (2) which is inserted into a bore in a lens and is secured by means of a plug (3) in such manner that the wire is urged into positive engagement with axially extending grooves in a wall of the bore. |
1. Spectacles comprising a bridge connecting two lenses, and side pieces mounted on the lenses for carrying spectacle bows, the lenses being connected to the side pieces and to the bridge by an attachment means; wherein at least one attachment means comprises a U-shaped wire loop which is inserted into a bore in a lens and is secured by a plug in such manner that the wire is urged into positive engagement with axially extending grooves in a wall of the bore. 2. Spectacles according to claim 1, wherein the plug is a plug of a synthetic material. 3. Spectacles according to claim 1, wherein the plug is secured by an adhesive. 4. Spectacles according to claim 3, wherein the adhesive is a radiation-activated adhesive, an epoxy-resin based adhesive, a hot-melt-type adhesive, or a thermoplastic synthetic material. 5. Attachment means for spectacles, with which spectacle lenses are connected to spectacles side pieces and to a spectacles bridge, wherein at least one attachment means comprises a U-shaped wire loop which is inserted into a bore in a lens and is secured by a plug in such a manner that the wire is urged into positive engagement with axially extending grooves in a wall of the bore. 6. Spectacles according to claim 5, wherein the plug is a plug of a synthetic material. 7. Spectacles according to claim 5, wherein the plug is secured by an adhesive. 8. Spectacles according to claim 3, wherein the adhesive is a radiation-activated adhesive, an epoxy-resin based adhesive, a hot-melt-type adhesive, or a thermoplastic synthetic material. 9. Spectacles according to claim 2, wherein the plug is secured by an adhesive. 10. Spectacles according to claim 6, wherein the plug is secured by an adhesive. 11. Spectacles according to claim 9, wherein the adhesive is a radiation-activated adhesive, an epoxy-resin based adhesive, a hot-melt-type adhesive, or a thermoplastic synthetic material. |
<SOH> BACKGROUND OF THE INVENTION <EOH>The invention relates to spectacles and an attachment means. Lenses and parts of a mount of spectacles are usually connected together by means of screws, threaded sleeves or a threaded pin with a nut. These are usually safeguarded against rotation by being secured in two bores, or by a pin in a notch at the periphery of a lens. A much applied method is that of inserting a wire bent to U-shape into oblong holes in the lens. EP 0 561 763 A1 describes a lens holder for spectacles, comprising pairs of retaining pins which each engage in a respective bore in a spectacle lens and are supported by a mount portion of the spectacles, the retaining pins consisting of the free limbs of a U-shaped wire bracket which has a portion of its cross-piece that connects the two limbs together attached to the mount portion. EP 1 024 390 A1 describes a mount for bored spectacles, comprising a bridge connecting two lenses, and brackets which each have a pin-shaped attachment element, the pin-shaped attachment elements each having a wing-shaped attachment region, and the spectacle lenses having corresponding slot-like (bead-shaped) notches disposed at a distanced from the extreme edge of the lens for stress-free, rotation-proof, and form-fitting engagement with the widened attachment regions. Most of the attachment means known in the prior art require relatively difficult machining of the lenses. Furthermore, they are only insufficiently secure, for example by wire loops inserted in oblong holes. |
<SOH> SUMMARY OF THE INVENTION <EOH>An object of the invention to provide spectacles having a very small-sized attachment means which will nevertheless ensure a secure attachment of the lenses. The object is achieved in accordance with the invention by at least one attachment means having a U-shaped wire loop which is inserted in a bore in the lens and is secured by a plug in such manner that the wire is urged into positive engagement with axially extending grooves in the wall of the bore. The plug is preferably a plug of a synthetic material which additionally may be secured with the aid of an adhesive, if necessary. The adhesive used is either a radiation-activated adhesive, an epoxy-reins based adhesive, a hot-melt-type adhesive, or a thermoplastic synthetic material. A further object of the invention is to provide an attachment means of a very small size, which nevertheless ensures a secure attachment of the lenses. The object is achieved in accordance with the invention by at least one attachment means having a U-shaped wire loop which is inserted in a bore in the lens and is secured by a plug in such manner that the wire is urged into positive engagement with axially extending grooves in the wall of the bore. The plug is preferably a plug of a synthetic material which additionally may be secured with the aid of an adhesive, if necessary. The adhesive used is either a radiation-activated adhesive, an epoxy-reins based adhesive, a hot-melt type-adhesive, or a thermoplastic synthetic material. |
Method of diagnosing or prognosticating major respiratory bacterial pathogens in a subject |
Method of diagnosing and/or prognosticating HIV infection in a subject comprising the steps of (a) performing in vitro a measurement of the level of a marker in the form of (i) urokinase plasminogen activator receptor (uPAR), (ii) soluble urokinase plasminogen activator receptor (suPAR), (iii) urokinase-type plasminogen activator (uPA), (iv) one or more degradation products of (i), (ii) or (iii), and/or (v) an mRNA for (i), (ii) or (iii), in a biological fluid sample from a subject, and (b) using the measurement value obtained to evaluate the state of the subject. |
1. A method of diagnosing respiratory bacterial infections in a subject comprising the steps of (a) measuring in vitro the level of one or more markers selected from the group consisting of (i) urokinase plasminogen activator receptor (uPAR), (ii) soluble urokinase plasminogen activator receptor (suPAR), and (iii) one or more degradation products of (i) or (ii), in a biological fluid sample from the subject, and (b) comparing the level measured in the subject with that of a healthy control wherein a greater level compared to the healthy control indicates a respiratory bacterial infection. 2. A method according to claim 1, wherein the respiratory bacterial infection is a Streptococcus pneumoniae infection. 3. A method according to claim 1, wherein the respiratory bacterial infection is a Mycobacterium tuberculosis infection. 4. A method according to claim 1, wherein the biological fluid sample is a urine sample. 5. A method according to claim 1, wherein the measuring is done using a stick. 6. A method according to claim 1, wherein the measuring is done using ELISA. 7. A method of evaluating the progression of the state of a subject suffering from a respiratory bacterial infection Comprising (a) measuring in vitro the level of one or more markers selected from the group consisting of (i) urokinase plasminogen activator receptor (uPAR), (ii) soluble urokinase plasminogen activator receptor (suPAR), and (iii) one or more degradation products of (i) or (ii), in each of a number of biological fluid samples from the subject, wherein the samples are obtained at different points in time, and (b) comparing the measured levels, wherein a decrease in the levels over time indicates an improvement of the state of the subject. 8. A method of evaluating the progression of the state of a subject suffering from a respiratory bacterial infection comprising a) measuring in vitro the level of one or more markers selected from the group consisting of (i) urokinase plasminogen activator receptor (uPAR), (ii) soluble urokinase plasminogen activator receptor (suPAR), and (iii) one or more degradation products of (i) or (ii), in each of a number of biological fluid samples from the subject, wherein the samples are obtained at different points in time, and (b) comparing the measured levels, wherein a decrease in the levels over time indicates an improvement of the state of the subject. 9. A method according to claim 8, wherein respiratory bacterial infection is a Steptococcus pneumoniae infection. 10. A method according to claim 8, wherein the respiratory bacterial infection is a Mycobacterium tuberculosis infection. 11. A method according to claim 8, wherein the subject is undergoing a treatment regimen. 12. A kit for evaluating the state of a subject suffering from a respiratory bacterial infection comprising a) an immobilized capture agent capable of capturing one or more markers selected from the group consisting of (i) urokinase plasminogen activator receptor (uPAR), (ii) soluble urokinase plasminogen activator receptor (suPAR), and (iii) one or more degradation products of (i) or (ii), and b) a binding partner capable of binding to the said marker, the binding partner comprising c) a label system. 13. A kit according to claim 12, wherein the respiratory bacterial infection is Streptococcus pneumoniae. 14. A kit according to claim 12, wherein the respiratory bacterial infection is a Mycobacterium tuberculosis. 15. A kit according to claim 12, wherein the capture agent is an antibody to a marker. 16. A kit according to claim 12, wherein the binding partner is an antibody to a marker. 17. A kit according to claim 12, wherein the capture agent is immobilized on a stick. |
<SOH> BACKGROUND OF THE INVENTION <EOH>The cellular receptor for urokinase (uPAR, CD87) plays multiple functions in cell migration, cell adhesion, pericellular proteolysis and tissue remodeling. uPAR is expressed by most leukocytes including monocytes, macrophages, neutrophils and platelets. uPAR is an activation antigen in monocytes and T cells and T-cells from HIV-1 infected individuals express elevated levels of uPAR 1 , 1994. HIV-1 infection of leukocytes in vitro causes up-regulation of uPAR cell surface expression in a process which appear to be coordinated temporally with the onset of viral replication 2 . uPAR may be shed from the cell surface generating a soluble form of the receptor (suPAR) lacking the GPI-anchor. The shedding mechanism is poorly understood but may occur by GPI-specific phospholipase D catalyzed hydrolytic cleavage of the GPI-anchor). Soluble forms of uPAR (suPAR) has been identified in cell culture supernatants and in diverse biological fluids such as tumor ascites, cystic fluid, serum, plasma and recently also in urine Serum, plasma and urine levels of suPAR are elevated in patients suffering from different types of cancer 4 , the paroxysmal nocturnal hemoglobinuria syndrome (PNH) syndrome 5 , and in rheumatoid arthritis patients 6 . The plasma level of suPAR is furthermore a prognostic marker for overall survival in patients suffering from HIV-1 infection 7 . The cellular origin of circulating suPAR is not known. Many, if not all, cells which express uPAR also shed soluble forms of the receptor when cultured in vitro. The source of excess serum suPAR in cancer patients has been suggested to derive from the cancer cells and/or tumor-infiltrating macrophages as these cells often express high levels of uPAR and experiments using xenografted mice carrying human tumors have indeed demonstrated that the tumor tissue does release suPAR to the circulation and urine 8 . |
<SOH> SUMMARY OF THE INVENTION <EOH>The technical problem addressed by the present invention is to provide a novel marker for diagnosing and prognosticating major respiratory bacterial pathogens, in particular Streptococcus pneumoniae and Mycobacterium tuberculosis . A further technical problem addressed by the present invention is to provide a marker of the said type, which is simple and affordable to measure. The present invention has provided a solution to the above technical problems, the invention being directed to a method of diagnosing or prognosticating major respiratory bacterial pathogens, such as Streptococcus pneumoniae and Mycobacterium tuberculosis in a subject comprising the steps of (a) performing in vitro a measurement of the level of one or more markers in the form of (i) urokinase plasminogen activator receptor (uPAR), (ii) soluble urokinase plasminogen activator receptor (suPAR), and/or (iii) one or more degradation products of (i) or (ii), in a biological fluid sample from a subject, and (b) using the measurement value obtained to evaluate the state of the subject. The invention is based on the surprising discovery that soluble uPAR (suPAR) is present in elevated levels in serum, plasma and urine of patients with two major respiratory bacterial pathogens, Streptococcus pneumoniae and Mycobacterium tuberculosis , and that the level of suPAR is useful as a diagnostic marker. Also, the level of suPAR in individuals with two major respiratory bacterial pathogens, Streptococcus pneumoniae and Mycobacterium tuberculosis is prognostic for the development of the disease and death. The suPAR level is a novel and highly diagnostic and prognostic factor, even in the context of other known prognostic factors related to Streptococcus pneumoniae or Mycobacterium tuberculosis infection of the lung. Furthermore, the present invention is based on the recognition that the amount of suPAR is correlated to the amount of uPAR and that therefore the amounts of uPAR is equally suitable as diagnostic and prognostic indicators of tuberculosis infection. A further advantage of the invention is that measurement of suPAR can be performed using e.g. a simple ELISA technique or even a stick and may therefore provide a very inexpensive, simple and quick supplement to the currently used prognostic tools for persons infected with tuberculosis. Thus, in developing countries without the financial possibility to carry out the costly assays used in the western world, suPAR levels could be used 1) to determine tuberculosis status (diagnosis), 2) to select patients for treatment (prognosis), and 3) to monitor the progress of treatment. Furthermore, the present invention involves the advantage that while suPAR levels can be measured very simply, using e.g. a urine sample or sputum sample, which is easy to obtain, conventional diagnostic and prognostic tests for e.g. tuberculosis are uncertain, complex and involve e.g. growth in culture of sputum, clinical testing and chest x-ray. The invention further relates to a method of evaluating the progression of the state of a subject suffering from a major respiratory bacterial pathogen, such as tuberculosis or Streptococcus pneumoniae comprising the steps of (a) performing in vitro a measurement of the level of one or more markers in the form of (i) urokinase plasminogen activator receptor (uPAR), (ii) soluble urokinase plasminogen activator receptor (suPAR), and/or (iii) one or more degradation products of (i) or (ii), in each of a number of biological fluid samples from a subject, wherein the samples are obtained at different points in time, and (b) using the measurement values obtained to evaluate the progression of the state of the subject. This method may be used to continuously monitor the state e.g. the treatment efficacy of the patient. Finally, the present invention relates to an ELISA-kit and stick-kit utilizing the above knowledge. |
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