The invention is directed to acylhydrazones compounds of Formula I:

The present invention relates to acylhydrazones as inhibitors of tyrosine kinases, including c-Met. Acylhydrazones known in the art, including those with therapeutic properties, include: CHEMCATS Accession No. 2004:3793350 Ambinter Stock Screening Collection. (1 Jan. 2004); WO 2003037328 (oxindole hydrazide modulators of protein tyrosine phosphatases); WO 2005005378 (indolinone hydrazides as C-Met inhibitors); WO 2004056178 (pesticidal chloropyridinamino derivatives); US 2004067996 (hydantoins as inhibitors of matrix metalloproteinases and/or TNF-α converting enzyme (TACE)); WO 2003097649 (1-oxa-dibenzoazulenes as inhibitors of tumor necrosis factor production and intermediates for the preparation thereof); WO 2003037328 (oxindole hydrazide modulators of protein tyrosine phosphatases (PTPs)); WO 2002096426 (spiro-fused hydantoin derivatives as inhibitors of matrix metalloproteinases); DE 10117823 and WO 2002083630 (ethanediamides as inhibitors of blood coagulation factor Xa for the treatment of thromboembolic illnesses); WO 2002040507 (novel compounds for use in radioimmunoscintigraphy and/or radioimmunotherapy of cancers); EP 1193248 and WO 2002028823 (arylmalonamides and -malonamic esters with as Factor VIIa inhibitors with antithrombotic activity); WO 2002000661 (pyrrolo[2,3-d]pyrimidines as immunosuppressive agents); DE 19946289 and WO 2001023386 (2-phenyl-5,6-dihydro-imidazo[4,5,1-jk][1,4]benzodiazepin-7(4H)-ones as poly(ADP ribose) polymerase inhibitors); WO 2000071511 (benzamidines as inhibitors of factor Xa); WO 2000071493 (benzamidines and arylamidines as inhibitors of factor Xa); WO 2000071509 (benzamidines and arylamidines as inhibitors of factor Xa); U.S. Pat. No. 6,075,044 (Isobenzofurandione and hydrazonodihydroindolone derivatives as protozoacides, acting as inhibitors of purine salvage phosphoribosyltransferases); JP 11302173 (Benzamide derivatives as histone deacetylase inhibitors for treating tumors and other diseases); WO 9951579 ([[[(alkoximino)alkoxy]methyl]phenyl]aloximinoacetates and analogs as agrochemical fungicides); JP 11015090 (silver halide photographic material for printing platemaking); JP 11007093 (photographic emulsion containing high-sensitive oxalylhydrazine derivative for graphic arts); WO 9901434 (imidazole-containing quinoline and benzazepine derivatives as inhibitors of farnesyl protein transferase); DE 19829229 and U.S. Pat. No. 6,235,787 (hydroxycarbamoylalkylcarboxylic acid hydrazides as inhibitors of tumor necrosis factor and transforming growth factor release); WO 9825901 (spiro[indolinone] derivatives as vasopressin V2 receptor antagonists); WO 9739748 (acrylic acids as modulators of molecules with phosphotyrosine recognition units); WO 9731910 (heterocyclic fibrinogen receptor antagonists); WO 9729073 (substituted amide derivatives as protein-farnesyl transferase inhibitors); U.S. Pat. No. 5,550,003 (silver halide photographic photosensitive material); EP 694808 (Process of forming super high-contrast negative images and silver halide photographic material and developer being used therefore); and EP 672659 (L-Arginine aldehyde peptide derivatives useful as antithrombotic agents).
Protein kinases are enzymatic components of the signal transduction pathways which catalyze the transfer of the terminal phosphate from ATP to the hydroxy group of tyrosine, serine and/or threonine residues of proteins. Thus, compounds which inhibit protein kinase functions are valuable tools for assessing the physiological consequences of protein kinase activation. The overexpression or inappropriate expression of normal or mutant protein kinases in mammals has been a topic of extensive study and has been demonstrated to play a significant role in the development of many diseases, including diabetes, angiogenesis, psoriasis, restenosis, ocular diseases, schizophrenia, rheumatoid arthritis, atherosclerosis, cardiovascular disease and cancer. The cardiotonic benefits of kinase inhibition has also been studied. In sum, inhibitors of protein kinases have particular utility in the treatment of human and animal disease.
The hepatocyte growth factor (HGF) (also known as scatter factor) receptor, c-Met, is a receptor tyrosine kinase which regulates cell proliferation, morphogenesis, and motility. The c-Met gene is translated into a 170 kD protein which is processed into a cell surface receptor composed of a 140 kD β transmembrane subunit and 50 kD glycosylated extracellular α subunit.
Mutations in c-Met, over-expression of c-Met and/or HGF/SF, expression of c-Met and HGF/SF by the same cell, and overexpression and/or aberrant c-Met signaling is present in a variety of human solid tumors and is believed to participate in angiogenesis, tumor development, invasion, and metastasis.
Cell lines with uncontrolled c-Met activation, for example, are both highly invasive and metastatic. A notable difference between normal and transformed cells expressing c-Met receptor is that phosphorylation of the tyrosine kinase domain in tumor cells is often independent of the presence of ligand.
C-Met mutations/alterations have been identified in a number of human diseases, including tumors and cancers—for instance, hereditary and sporadic human papillary renal carcinomas, breast cancer, colorectal cancer, gastric carcinoma, glioma, ovarian cancer, hepatocellular carcinoma, head and neck squamous cell carcinomas, testicular carcinoma, basal cell carcinoma, liver carcinoma, sarcoma, malignant pleural mesothelioma, melanoma, multiple myeloma, osteosarcoma, pancreatic cancer, prostate cancer, synovial sarcoma, thyroid carcinoma, non-small cell lung cancer (NSCLC) and small cell lung cancer, transitional cell carcinoma of urinary bladder, testicular carcinoma, basal cell carcinoma, liver carcinoma—and leukemias, lymphomas, and myelomas—for instance, acute lymphocytic leukemia (ALL), acute myeloid leukemia (AML), acute promyelocytic leukemia (APL), chronic lymphocytic leukemia (CLL), chronic myeloid leukemia (CML), chronic neutrophilic leukemia (CNL), acute undifferentiated leukemia (AUL), anaplastic large-cell lymphoma (ALCL), prolymphocytic leukemia (PML), juvenile myelomonocyctic leukemia (JMML), adult T-cell ALL, AML with trilineage myelodysplasia (AML/TMDS), mixed lineage leukemia (MLL), myelodysplastic syndromes (MDSs), myeloproliferative disorders (MPD), multiple myeloma, (MM), myeloid sarcoma, non-Hodgkin's lymphoma and Hodgkin's disease (also called Hodgkin's lymphoma).
See Maulik G, Shrikhande A, Kijima T, Ma P C, Morrison P T, Salgia R., Role of the hepatocyte growth factor receptor, c-Met, in oncogenesis and potential for therapeutic inhibition. Cytokine Growth Factor Rev. 2002 February; 13(1):41-59, and cites therein: Bieche, M. H. Champeme and R. Lidereau, Infrequent mutations of the MET gene in sporadic breast tumours (letter). Int. J. Cancer 82 (1999), pp. 908-910; R. L. Camp, E. B. Rimm and D. L. Rimm, Met expression is associated with poor outcome in patients with axillary lymph node negative breast carcinoma. Cancer 86 (1999), pp. 2259-2265; L. Nakopoulou, H. Gakiopoulou, A. Keramopoulos et al., c-met tyrosine kinase receptor expression is associated with abnormal beta-catenin expression and favourable prognostic factors in invasive breast carcinoma. Histopathology 36 (2000), pp. 313-325; C. Liu, M. Park and M. S. Tsao, Over-expression of c-met proto-oncogene but not epidermal growth factor receptor or c-erbB-2 in primary human colorectal carcinomas. Oncogene. 7 (1992), pp. 181-185; K. Umeki, G. Shiota and H. Kawasaki, Clinical significance of c-met oncogene alterations in human colorectal cancer. Oncology 56 (1999), pp. 314-321; H. Kuniyasu, W. Yasui, Y. Kitadai et al., Frequent amplification of the c-met gene in scirrhous type stomach cancer. Biochem. Biophys. Res. Commun. 189 (1992), pp. 227-232; H. Kuniyasu, W. Yasui, H. Yokozaki et al., Aberrant expression of c-met mRNA in human gastric carcinomas. Int. J. Cancer 55 (1993), pp. 72-75; W. S. Park, R. R. Oh, Y. S. Kim et al., Absence of mutations in the kinase domain of the Met gene and frequent expression of Met and HGF/SF protein in primary gastric carcinomas. Apmis 108 (2000), pp. 195-200; J. H. Lee, S. U. Han, H. Cho et al., A novel germ line juxtamembrane Met mutation in human gastric cancer. Oncogene 19 (2000), pp. 4947-4953; T. Moriyama, H. Kataoka, H. Tsubouchi et al., Concomitant expression of hepatocyte growth factor (HGF), HGF activator and c-met genes in human glioma cells in vitro. FEBS Lett. 372 (1995), pp. 78-82; Y. W. Moon, R. J. Weil, S. D. Pack et al., Missense mutation of the MET gene detected in human glioma. Mod. Pathol. 13 (2000), pp. 973-977; M. Di Renzo, M. Olivero, T. Martone et al., Somatic mutations of the met oncogene are selected during metastatic spread of human HNSC carcinomas. Oncogene 19 (2000), pp. 1547-1555; K. Suzuki, N. Hayashi, Y. Yamada et al., Expression of the c-met proto-oncogene in human hepatocellular carcinoma. Hepatology 20 (1994), pp. 1231-1236; W. S. Park, S. M. Dong, S. Y. Kim et al., Somatic mutations in the kinase domain of the Met/hepatocyte growth factor receptor gene in childhood hepatocellular carcinomas. Cancer Res. 59 (1999), pp. 307-310; L. Schmidt, K. Junker, G. Weirich et al., Two North American families with hereditary papillary renal carcinoma and identical novel mutations in the MET proto-oncogene. Cancer Res. 58 (1998), pp. 1719-1722; J. Fischer, G. Palmedo, R. von Knobloch et al., Duplication and over-expression of the mutant allele of the MET proto-oncogene in multiple hereditary papillary renal cell tumours. Oncogene. 17 (1998), pp. 733-739; Z. Zhuang, W. S. Park, S. Pack et al., Trisomy 7-harbouring non-random duplication of the mutant MET allele in hereditary papillary renal carcinomas. Nat Genet 20 (1998), pp. 66-69; M. Olivero, G. Valente, A. Bardelli et al., Novel mutation in the ATP-binding site of the MET oncogene tyrosine kinase in a HPRCC family. Int. J. Cancer 82 (1999), pp. 640-643; L. Schmidt, K. Junker, N. Nakaigawa et al., Novel mutations of the MET proto-oncogene in papillary renal carcinomas. Oncogene 18 (1999), pp. 2343-2350; M. Jucker, A. Gunther, G. Gradl et al., The Met/hepatocyte growth factor receptor (HGFR) gene is over-expressed in some cases of human leukemia and lymphoma. Leuk. Res. 18 (1994), pp. 7-16; E. Tolnay, C. Kuhnen, T. Wiethege et al., Hepatocyte growth factor/scatter factor and its receptor c-Met are over-expressed and associated with an increased microvessel density in malignant pleural mesothelioma. J. Cancer Res. Clin. Oncol. 124 (1998), pp. 291-296; J. Klominek, B. Baskin, Z. Liu et al., Hepatocyte growth factor/scatter factor stimulates chemotaxis and growth of malignant mesothelioma cells through c-met receptor. Int. J. Cancer 76 (1998), pp. 240-249; Thirkettle, P. Harvey, P. S. Hasleton et al., Immunoreactivity for cadherins, HGF/SF, met, and erbB-2 in pleural malignant mesotheliomas. Histopathology 36 (2000), pp. 522-528; P. G. Natali, M. R. Nicotra, M. F. Di Renzo et al., Expression of the c-Met/HGF receptor in human melanocytic neoplasms: demonstration of the relationship to malignant melanoma tumour progression. Br. J. Cancer. 68 (1993), pp. 746-750; O. Hjertner, M. L. Torgersen, C. Seidel et al., Hepatocyte growth factor (HGF) induces interleukin-11 secretion from osteoblasts: a possible role for HGF in myeloma-associated osteolytic bone disease. Blood 94 (1999), pp. 3883-3888; C. Liu and M. S. Tsao, In vitro and in vivo expressions of transforming growth factor-alpha and tyrosine kinase receptors in human non-small-cell lung carcinomas. Am. J. Pathol. 142 (1993), pp. 1155-1162; M. Olivero, M. Rizzo, R. Madeddu et al., Over-expression and activation of hepatocyte growth factor/scatter factor in human non-small-cell lung carcinomas. Br J. Cancer 74 (1996), pp. 1862-1868; E. Ichimura, A. Maeshima, T. Nakajima et al., Expression of c-met/HGF receptor in human non-small cell lung carcinomas in vitro and in vivo and its prognostic significance. Jpn. J. Cancer Res. 87 (1996), pp. 1063-1069; Takanami, F. Tanana, T. Hashizume et al., Hepatocyte growth factor and c-Met/hepatocyte growth factor receptor in pulmonary adenocarcinomas: an evaluation of their expression as prognostic markers. Oncology 53 (1996), pp. 392-397; J. M. Siegfried, L. A. Weissfeld, J. D. Luketich et al., The clinical significance of hepatocyte growth factor for non-small cell lung cancer. Ann Thorac. Surg. 66 (1998), pp. 1915-1918; M. Tokunou, T. Niki, K. Eguchi et al., c-MET expression in myofibroblasts: role in autocrine activation and prognostic significance in lung adenocarcinoma. Am J. Pathol. 158 (2001), pp. 1451-1463; R. Ferracini, M. F. Di Renzo, K. Scotlandi et al., The Met/HGF receptor is over-expressed in human osteosarcomas and is activated by either a paracrine or an autocrine circuit. Oncogene 10 (1995), pp. 739-749; M. F. Di Renzo, M. Olivero, D. Katsaros et al., Over-expression of the Met/HGF receptor in ovarian cancer. Int. J. Cancer 58(1994), pp. 658-662; H. M. Sowter, A. N. Corps and S. K. Smith, Hepatocyte growth factor (HGF) in ovarian epithelial tumour fluids stimulates the migration of ovarian carcinoma cells. Int. J. Cancer 83 (1999), pp. 476-480; M. Ebert, M. Yokoyama, H. Friess et al., Co-expression of the c-met proto-oncogene and hepatocyte growth factor in human pancreatic cancer. Cancer Res. 54 (1994), pp. 5775-5778; L. L. Pisters, P. Troncoso, H. E. Zhau et al., c-met proto-oncogene expression in benign and malignant human prostate tissues. J. Urol. 154 (1995), pp. 293-298; P. A. Humphrey, X. Zhu, R. Zarnegar et al., Hepatocyte growth factor and its receptor (c-MET) in prostatic carcinoma. Am J. Pathol. 147 (1995), pp. 386-396; K. Rygaard, T. Nakamura, M. Spang-Thomsen et al., Expression of the proto-oncogenes c-met and c-kit and their ligands, hepatocyte growth factor/scatter factor and stem cell factor, in SCLC cell lines and xenografts. Br J. Cancer 67 (1993), pp. 37-46; Y. Oda, A. Sakamoto, T. Saito et al., Expression of hepatocyte growth factor (HGF)/scatter factor and its receptor c-MET correlates with poor prognosis in synovial sarcoma. Hum. Pathol. 31 (2000), pp. 185-192; M. F. Di Renzo, M. Olivero, G. Serini et al., Over-expression of the c-MET/HGF receptor in human thyroid carcinomas derived from the follicular epithelium. J. Endocrinol. Invest 18 (1995), pp. 134-139; K. Gohji, M. Nomi, Y. Niitani et al., Independent prognostic value of serum hepatocyte growth factor in bladder cancer. J. Clin. Oncol. 18 (2000), pp. 2963-2971.
Because of the role of aberrant HGF/SF-Met signaling in the pathogenesis of various human cancers, inhibitors of c-Met receptor tyrosine kinase have broad applications in the treatment of cancers in which Met activity contributes to the invasive/metastatic phenotype, including those in which c-Met is not overexpressed or otherwise altered. Inhibitors of c-Met also inhibit angiogenesis and therefore are believed to have utility in the treatment of diseases associated with the formation of new vasculature, such as rheumatoid, arthritis, retinopathy. See, Michieli P, Mazzone M, Basilico C, Cavassa S, Sottile A, Naldini L, Comoglio P M. Targeting the tumor and its microenvironment by a dual-function decoy Met receptor. Cancer Cell. 2004 July; 6(1):61-73.
Over-expression of c-Met is also believed to be a potentially useful predictor for the prognosis of certain diseases, such as, for example, breast cancer, non-small cell lung carcinoma, pancreatic endocrine neoplasms, prostate cancer, esophageal adenocarcinoma, colorectal cancer, salivary gland carcinoma, diffuse large B-cell lymphoma and endometrial carcinoma.
See Herrera L J, El-Hefnawy T, Queiroz de Oliveira P E, Raja S, Finkelstein S, Gooding W, Luketich J D, Godfrey T E, Hughes S J., The HGF Receptor c-Met Is Overexpressed in Esophageal Adenocarcinoma. Neoplasia. 2005 January; 7(1):75-84; Zeng Z, Weiser M R, D'Alessio M, Grace A, Shia J, Paty P B., Immunoblot analysis of c-Met expression in human colorectal cancer: overexpression is associated with advanced stage cancer. Clin Exp Metastasis. 2004; 21(5):409-17; He Y, Peng Z, Pan X, Wang H, Ouyang Y. [Expression and correlation of c-Met and estrogen receptor in endometrial carcinomas] Sichuan Da Xue Xue Bao Yi Xue Ban. 2003 January; 34(1):78-9, 88 (English Abstract Only); Tsukinoki K, Yasuda M, Mori Y, Asano S, Naito H, Ota Y, Osamura R Y, Watanabe Y. Hepatocyte growth factor and c-Met immunoreactivity are associated with metastasis in high grade salivary gland carcinoma. Oncol Rep. 2004 November; 12(5):1017-21; Kawano R, Ohshima K, Karube K, Yamaguchi T, Kohno S, Suzumiya J, Kikuchi M, Tamura K. Prognostic significance of hepatocyte growth factor and c-MET expression in patients with diffuse large B-cell lymphoma. Br J Haematol. 2004 November; 127(3):305-7; Lengyel E, Prechtel D, Resau J H, Gauger K, Welk A, Lindemann K, Salanti G, Richter T, Knudsen B, Vande Woude G F, Harbeck N. C-Met overexpression in node-positive breast cancer identifies patients with poor clinical outcome independent of Her2/neu. Int J Cancer. 2005 Feb. 10; 113(4):678-82; Hansel D E, Rahman A, House M, Ashfaq R, Berg K, Yeo C J, Maitra A. Met proto-oncogene and insulin-like growth factor binding protein 3 overexpression correlates with metastatic ability in well-differentiated pancreatic endocrine neoplasms. Clin Cancer Res. 2004 Sep. 15; 10(18 Pt 1):6152-8; Knudsen B S, Edlund M. Prostate cancer and the met hepatocyte growth factor receptor. Adv Cancer Res. 2004; 91:31-67; D Masuya, C Huang, D Liu, T Nakashima, et al., The tumour-stromal interaction between intratumoral c-Met and stromal hepatocyte growth factor associated with tumour growth and prognosis in non-small-cell lung cancer patients. British Journal of Cancer. 2004; 90:1552-1562; Ernst Lengyel, Dieter Prechtel, James H. Resau, Katja Gauger, et al. C-Met overexpression in node-positive breast cancer identifies patients with poor clinical outcome independent of Her2/neu. Int. J. Cancer 2005; 113: 678-682.

Abstract: where R1, R2 and A are as defined herein, the use of such compounds as protein tyrosine kinase modulators, particularly inhibitors of c-Met, and the use of such compounds to reduce or inhibit kinase activity of c-Met in a cell or a subject, and modulate c-Met expression in a cell or subject, and the use of such compounds for preventing or treating in a subject a cell proliferative disorder and/or disorders related to c-Met. The present invention is further directed to pharmaceutical compositions comprising the compounds of the present invention and to methods for treating conditions such as cancers and other cell proliferative disorders.


An electronic component includes a semiconductor chip and a leadframe. The leadframe includes a metal coating pattern on its underside to facilitate the application of solder to the electronic component. The metal coating pattern includes wetting regions that are wettable with solder material and anti-wetting regions that are unwettable with solder material, and the electronic component includes solder deposits formed on the wetting regions on the underside of the component.

To simplify surface mounting, electronic components with outer contact surfaces on the underside are individually provided with fluxes or with solder coatings on the outer contact surfaces. An application of solder of this nature is intended to effect electrical connection to the higher-level electronic circuit. Application of solder to individual components is complex and results in solder deposits of different heights on the outer contact surfaces for different outer surface sizes, which is detrimental to reliable mounting and reliable electrical connection to the higher-level electronic circuit.

Electronic component and leadframe for producing the component


An instrument (“artificial athlete”) for characterizing, from the biomechanical standpoint, a treading surface, such as natural grass cover or synthetic grass flooring, is configured for: dropping a weight from a given height on the surface, producing the conversion of kinetic energy of falling of the weight into deformation energy of the surface, the deformation energy being able to be restored by the surface to the weight, bringing about its return/bouncing back upwards; and detecting at least one parameter representing the process of restitution of the deformation energy by the surface to the weight, the parameter identifying the characteristics of tread of the surface.

1. Field of the Invention
The present invention relates to techniques for the characterization of treading surfaces.
2. Description of the Related Art
There exist various known techniques, some of which form the subject of specific standards, designed to enable the characterization of treading surfaces. These techniques have been developed, for example, for identifying, in a reasonably objective way, the characteristics of tread of surfaces such as, for example, floorings made of synthetic material.
These known techniques can be used also for the characterization of surfaces designed for practicing sports activities.
For instance, the standard DIN 18035/7 envisages specific criteria for measuring and calculating a parameter of absorption of energy KA (abbreviation of the German word Kraftabbau), which can be detected using an apparatus known as "artificial athlete of Berlin". The requisites established by the International Federation of Football Association (FIFA) envisage that pitches for playing soccer will have values of KA comprised in the range between 55% and 70%.
The above DIN standard then envisages the possibility of measuring and calculating a parameter of standard deformation using another instrument commonly referred to as "artificial athlete of Stuttgart". The FIFA requisites envisage a range of values between 4 and 8 mm.
Further useful information on the subject can be drawn from the European Standard published at the level of draft in October 2003 as prEN14808.
The "artificial athletes" considered above base their operation on a weight (i.e., a body of predetermined weight) sustained by a base structure resting on the surface to be characterized. The weight is dropped from a given height onto the surface, and associated to the structure is a cup sustained by a spring, which will be struck by the weight as it falls.
In other types of artificial athletes, it is envisaged that the weight will strike the surface to be characterized at the end of its fall: in this case the front face (or impact face) of the weight carries, however, a spring, to which a sensor device for detecting deformation is associated.
In the course of the last few years, synthetic grass floorings of the type described, for example, in EP-A-0 377 925, U.S. Pat. No. 4,337,283, U.S. Pat. No. 5,958,527, U.S. Pat. No. 5,976,645 or EP-A-1 158 099 have found an increasingly wide application.
The solution described in the document cited last enables reproduction in a highly faithful manner of the characteristics of tread and of response to mechanical stresses (bumps, impacts of various nature, etc.) of natural grass cover or turf.
In order to exploit this possibility fully, it is important to identify, in a precise and faithful way—and as objectively as possible—, the characteristics of a given natural grass cover and the characteristics of the synthetic grass flooring (turf) which is desired to be able to reproduce, with the greatest faithfulness possible the characteristics of natural grass cover, this both with specific reference to the biomechanical parameters that essentially determine the interaction of athletes with the surface of the flooring that they use and as regards, for example, the characteristics of bouncing of a ball used for practicing sport on said flooring.
The tests conducted in the course of the last few years demonstrate, however, that the methods and the instruments of characterization of a traditional type, such as those to which reference has been made in the introductory part of the present description, are unable to provide a particularly precise and faithful characterization of a surface, such as, for example, a grass cover, whether natural or synthetic.

Method and instrument for characterizing treading surfaces, for instance for realizing synthetic turf surfaces


A large volume infusion dosage form of gemcitabine, comprising a stable large volume solution of gemcitabine or its pharmaceutically acceptable salt in an aqueous vehicle filled in a large volume infusion container, wherein the solution is ready-to-be-infused.

Gemcitabine, a synthetic pyrimidine nucleoside antineoplastic agent causes cellular arrest by inhibiting ribonucleotide reductase and DNA synthesis. It is used in the treatment of the various types of cancer such as non-small cell lung cancer (NSCLC) when given alone or together with cisplatin, pancreatic cancer, breast cancer, when given together with paclitaxel, in treatment of ovarian cancer when given together with carboplatin and in treatment of bladder cancer when given together with cisplatin. The existing parenteral gemcitabine hydrochloride injections are available either in the form of a sterile lyophilized powder or a concentrated solution. Neither of these forms can be directly administered to a patient, rather they require manipulation. It is extremely important that no microbial contamination occurs during this manipulation and the sterile nature of the product is preserved. Thus the procedure requires that the hospital staff follow recommended sterile technique. Deviation from recommended sterile technique poses a risk to the patient. Moreover, manual manipulation such as steps of reconstitution, dilution and incorporation into a sterile aqueous vehicle suitable for intravenous infusion can result in the wrong dose being administered or even in the error of infusing different drug in cases where the patient is prescribed combination chemotherapy with multiple drugs or other medication errors.
Gemcitabine preparations required for parenteral administration are currently available in the form of lyophilizates (Gemzar®), which must be reconstituted before administration to the patient. However, these freeze-dried preparations have considerable disadvantages. First of all, the process of preparing these lyophilisates is complicated and costly. Secondly, reconstitution requires additional working steps and undesirable risks of personnel involved. In particular, reconstitution of drug solutions from a dry substance can result in what has been called the 'spray-back effect,' which may result in further contamination and risk of personnel. As described above, other errors in handling can lead to serious problems such as deviation in the concentration of active substance, or microbial contamination. Further, it is reported (See Physician Desk Reference, Gemzar) that the maximum concentration for Gemzar® upon reconstitution, is 40 mg/mL. It is reported that at concentrations greater than 40 mg/mL may result in incomplete dissolution, and therefore should be avoided. Further, for Gemzar® like products which require reconstitution, normal safety precautions need to be observed when preparing and disposing of the infusion solution. Handling of such products needs to be carried out in a safety box. Use of protective coats and gloves is suggested. Particularly, the package insert states that if no safety box is available, the equipment should be supplemented with a mask and protective glasses. Further, the pack insert provides precaution that during the use of the concentrate product, there are chances that the preparation can come into contact with the eyes, which may cause serious irritation. Again, since there is a human intervention, there are chances that the solution can be spilled on the skin.
A study of prior art reveals that attempts have been made to solve the above described problems but none has led to a large volume infusion dosage form of gemcitabine wherein the dosage form is a stable solution of a gemcitabine or its pharmaceutically acceptable salt in an aqueous vehicle in a large volume infusion container. For example, United States Patent Application Number US20060089328 describes an injectable pharmaceutical composition comprising a solution of gemcitabine having a pH of about 3.5 to about 10 and a gemcitabine concentration of about 0.5 mg/ml to about 16 mg/ml. This patent application describes a solution of gemcitabine which is prepared by aseptic filtration having 2 ml filled aseptically into 2 ml perforable stopper vials. Anohter prior art, US20060154891, mentions the gemcitabine solutions to be ready-to-use and gemcitabine concentrates. However, it is to be noted that the "ready-to-use" solution is the one which is not reconstituted from a solid, such as a crystalline or an amorphous solid or a lyophilisate, immediately before it is administered to a patient. Thus, this prior art teaches a ready to use solution having an intervening step of dilution or mixing before administration.
It is important to note that the concentrate of the prior art, needs to be withdrawn and diluted with a vehicle suitable for infusion for suitable dose. Risks associated with such manipulation, for example, the appearance of particulates or crystalline drug in the perfusate remains a possibility. Further, for higher doses such as 1500 mg or above, more than one vials of prior art either having the preconcentrate or the lyophilized powder, may be required to achieve the dose as against the single ready to be infused solution of the present invention which can be immediately given to the patients, with accurate dose. The present invention thus enables the user to avoid steps of using more than one vial, a small volume parenteral container, to arrive at higher doses that are not equivalent in a single vial.
PCT publication Number WO2007037793 (herein after referred to as WO'793) teaches flexible containers having multiple chambers so that incompatible solutions in different compartments are isolated and the container allow selective sterile admixing to form a ready-to-infuse formulation prior to administration. Thus, a stable ready-to-infuse solution is absent in any of the chambers, rather a solution which may be unstable over time is formed before administration and administered immediately.
A particular problem encountered with a large volume gemcitabine solution is disclosed in Xu et al (J. Am. Pharm. Assoc., Vol 39, No 4, July/August 1999, page no 509-513). The authors found that when lyophilized gemcitabine (Gemzar®—Eli Lilly and Company) was reconstituted with aqueous vehicles and the infusion solution was stored at 4° C. for 14 days or more, crystals of gemcitabine appeared. These crystals did not dissolve upon warming to room temperature. Thus, the prior large volume infusion solution formed on reconstitution was unstable. The present inventors were confounded with the same problem and infusion solutions of gemcitabine showed appearance of crystals or particulates when they were stored at 2-8° C. or at room temperatures. The present inventors have now surprisingly found large volume infusion dosage form of gemcitabine wherein the dosage form is a "stable solution" of gemcitabine or its pharmaceutically acceptable salt in an aqueous vehicle in a large volume infusion container and wherein the solution is ready-to-infuse. The large volume infusion dosage form of the present invention is "stable" and "ready to be infused" gemcitabine large volume solution meaning thereby that the solution is stable over time, is sterile, has a volume in excess of 100 ml and can be directly infused intravenously without any intervening step of reconstitution or dilution or mixing.
Thus, the present invention can be said to solve the unmet need of ready to be infused solution dosage form of gemcitabine, which is a large volume infusion dosage form of gemcitabine wherein the dosage form is a solution of a gemcitabine or its pharmaceutically acceptable salt in an aqueous vehicle in a large volume infusion container and wherein the solution is ready-to-be infused. The present inventors surprisingly found that a large volume infusion solution in a large volume infusion container was stable after it was subjected to terminal sterilization. The gemcitabine solution of the invention is stable for extended periods of time in the liquid state, without having to undergo a step of freeze-drying or reconstitution. That is it represents a substantial advancement over the art, and a major convenience to potential patients. The ready to infuse solution avoids the inconvenience of diluting a concentrated small volume gemcitabine hydrochloride parenteral formulation into infusion diluents prior to infusion, as well as eliminates the risk of microbiological contamination during aseptic handling and any potential calculation or dilution error.

Ready to be infused gemcetabine solution


Systems, apparatuses, and method for synchronizing port entry into a lowest power state are described. All logic of a port placed into an intermediate state prior to entry into the lowest power state.

MIPI's M-PHY (a physical layer technology that is developed for mobile platforms) offers two transmission modes: low speed and high speed, each supporting multiple speed gears, and will also support several power-save states: STALL for the high-speed mode, SLEEP for the low-speed mode, and HIBERN8. STALL and SLEEP are optimized for a quick wakeup in their respective transmission modes, whereas HIBERN8 is a very low-power mode, which has a longer wakeup time. M-PHY is also defined to support optical links.

Systems, apparatuses, and methods for synchronizing port entry into a low power state


The invention features a method for inhibiting proliferation of osteoblasts in a mammal in need of such inhibition. The method entails administering PF4. PF4 can be used to treat both diseases characterized by primary changes in osteoblastic cell function/activity (e.g., ossifying fibroma and fibrous dysplasia, osteoblastoma and osteoid osteoma, and osteosarcoma) and diseases or systemic conditions affecting bone in which abnormal osteoblastic cell function/activity is a secondary effect (e.g., acromegaly, hypercalcemia, primary or secondary hyperparathyroidism, hyperthyroidism, osteoporosis, or Paget's disease of bone). In addition, PF4 may be used to treat diseases associated with localized changes in bone metabolism in which abnormal osteoblastic cell function/activity contributes to pathogenic bone changes. For example, PF4 can be used to treat periodontal disease (localized, inflammation-induced bone loss), rheumatoid arthritis and osteoarthritis (localized, inflammation-induced bone loss) localized osteoporosis, mastocytosis, multiple myeloma, and bone metastases of various tumors. Because of its inhibitory effect on osteoblastic cell proliferation, PF4 can be used to treat bone abnormalities associated with either undesired osteoblastic cell proliferation or undesired osteoblastic cell function or activity.

Platelet factor 4 (PF4) is a well-known protein which has been completely sequenced (Deuel et al. Proc. Natl. Acad. Sci. USA 78:4585, 1981). It is a 70-residue secretable platelet protein with a molecular weight of approximately 7.8 Kd which is released during platelet aggregation.
PF4 possesses characteristic structural features of the pro-inflammatory proteins interleukin-8 and .beta.-thromboglobulin.
PF4 has been reported to inhibit the growth of melanoma and colon carcinoma in vivo, but not in vitro (Sharpe et al. (1990) J. Natl. Cancer Inst. 82:848-853; Maione et al. (1991) Cancer Res. 51:2077-2083).
It has been suggested that PF4 may inhibit growth of Kaposi sarcoma cells in vitro (Zucker et al. (1991) Proc. Soc. Exp. Biol. Med. 198:693-702; Miles et al. (1991) [abstract] VII International Conference on Aids (1991) Florence, Italy).
Hiti-Harper et al. (Science 199:99, 1978) report that PF4 inhibits collagenase derived from cultured human skin or human granulocytes.
Horton et al. (Biochim. Biophys. Acta 630:459, 1980) report that PF4 inhibits parathyroid hormone-stimulated .sup.45 Ca release from fetal rat bone in vitro.

Use of platelet factor 4 to inhibit osteoblast proliferation

University of Louisville Research Foundation, Inc.


An electric depositing drum is provided for a copper foil producing machine for producing copper foil. In the electrically depositing drum 3 provided with a top skin 2 on an outer circumferential surface of an outer circumferential plate 1a of an inner drum 1, nickel plating or brass plating is effected onto an inner circumferential surface of the top skin 2 to form a plated layer 2m.

The present invention relates to an electrically depositing drum in a copper foil producing machine for producing copper foil.
Many approaches and improvements have conventionally been made for electrically depositing and forming copper foil having a uniform thickness and a uniform smooth surface on a surface of an electrically depositing drum. In particular, conductivity of the top skin and conductivity and anti-corrosion property of outer circumferential plates of the top skin and an inner drum are improved to make it possible to produce excellent copper foil.
The anti-corrosion problem has recently been solved to some extent by the following steps. Namely, a titanium plate that is superior in anti-corrosion property to electrolyte is used as a top skin. This top skin is bonded on the surface of the inner drum. A titanium electrically depositing drum for forming copper foil having a uniform thickness and a uniform smooth surface on the outer circumferential surface of the titanium plate is used.
In this titanium electrically depositing drum, in general, the titanium plate is bonded on an outer circumferential portion of the inner drum made of soft steel or stainless steel. The copper foil is produced on the outer circumferential surface of the titanium plate by causing current to flow from the titanium plate to the inner drum through the outer circumferential portion. However, the conventional titanium electrically depositing drum suffers from the following problems concerning the conductivity.
i) Unless the contact and intimate bond between the titanium plate and the inner drum are sufficient, a local electric supply trouble occurs.
ii) As the inner drum is gradually corroded by the electrolyte, oxidized scales are formed on the inner drum. For this reason, the conductivity is locally deteriorated.
iii) In the case where the inner drum is made of iron system material, even if an expensive top skin like titanium is coated, when rust is generated on the inner drum, the conductivity of the titanium top skin is deteriorated to thereby offset the superiority of the titanium.
Accordingly, owing to the above-described problems concerning the conductivity, in the conventional titanium electrically depositing drum, there is a fear that a color change caused by the non-uniformity of the thickness of the copper foil, the abnormal precipitation, local heat, i.e., a so-called hot spot would occur. In order to enhance the productivity and the quality of the product, it is necessary to improve the conductivity.


A data decoding circuit of the present invention can regenerate a bit synchronization signal from a data received by using a code such as a split-phase code and Manchester code in which a binary value can be detected through a transition of voltage at a central area of a bit cell and transform the received data into a serial binary data. The data decoding circuit includes an edge detection section for detecting a transition point in the received data; a pulse generating section for generating a phase comparing timing signal having a pulse width of substantially 1/(4.times.fs) when fs is a data transfer frequency and a received data regenerating signal having a pulse width of substantially 1(2.times.fs) in synchronism with an output of the edge detection means; a phase synchronization oscillation section synchronized in phase with the phase comparing timing signal for outputting a signal having a frequency n times the data transfer frequency fs; and a sampling section including means for generating the bit synchronization signal by dividing a frequency of a signal outputted from the phase synchronization oscillation means into 1/n, means for sampling the received data regenerating signal based on the bit synchronization signal and means for transforming sampled signal into a serial binary data.

1. Field of the Invention
The present invention relates to a data decoding circuit for regenerating a bit synchronization signal from a data received by using a code such as-split-phase code and Manchester code in which a binary value can be detected through a transition of voltage at a central area of a bit cell and for transforming the received data into a serial binary data.
2. Description of the Related Art
To decode a data of split-phase code, Manchester code or the like, the prior art takes the following procedure. The edge of a received data is first detected by an edge detecting circuit, the output of which is then used to form a bit synchronization signal. A serial binary data was obtained by sampling the received data with the bit synchronization signal.
The bit synchronization signal was formed by a bit synchronization circuit which used a digital or analog phase-locked loop circuit.
One digital phase-locked loop circuit is described in Japanese Patent Application Laid-Open No. 60-227541 while one analog phase-locked loop circuit is described in Japanese Patent Application Laid-Open No. 5-14333.
The other references such as Japanese Patent Application Laid-Open No. 63-191433 and Japanese Patent Publication No. 3-3429 also describe a bit synchronization circuit for obtaining a bit synchronization signal.
When the split-phase code or Manchester code is to be decoded, there are following important conditions for that.
(1) Synchronism recovery time (or the number of data bits required to recover the synchronism) must be reduced when a data for a frame synchronization signal (or preamble data) is received (Japanese Patent Publication No. 3-3429).
(2) Synchronization must not be disturbed when the same data (e.g., one) is continuously inputted info a transferred data (Japanese Patent Application Laid-Open No. 62-241435 or Japanese Patent Application Laid-Open No. 5-14333).
(3) An encoded received data must be capable of being decoded even if it contains a jitter which may be .+-.18 nsec. at a transfer frequency of 10 MHz in a network according to IEEE 802.3 Standard (Japanese Patent Application Laid-Open No. 60-227541).
(4) The data decoding circuit can be formed easily as a semiconductor device (Japanese Patent Application Laid-Open No. 60-227541, Japanese Patent Publication No. 3-3429 or Japanese Patent Application Laid-Open No. 5-14333).
In order to code a data to be transmitted according to a standard and to transmit the encoded data, the data transmission uses a medium for propagating the encoded data, a transmitter for driving the data propagation medium and a receiver for receiving the encoded data through the medium and for decoding the received data at a receiving circuit to regenerate the original data.
In the prior art, the data decoding circuit digitizes a received return-to-zero (RZ) data at the receiving circuit to sample directly with a bit synchronization signal. The receiving circuit is thus required to reproduce exactly the pulse width, cycle and others of the received data. In other words, they are required to increase the response speed of a comparator used in the receiving circuit and also to bring the offset of the comparator near to zero as much as possible.
Such requirements raised problems in that, the current consumption is increased and that the circuit is increased in scale to make the semiconductor device more expensive.
When the data decoding circuit is formed as a semiconductor device, voltage-controlled oscillation circuit is normally used. It is desirable that even if the oscillation frequency of the voltage-controlled oscillation circuit is lowered, phase synchronization can be accomplished with a high precision.

Data decoding circuit, voltage-controlled oscillation circuit, data decoding system and electronic equipment


Methods of routing user designs in programmable logic devices (PLDs) having heterogeneous routing structures, i.e., PLDs including both high-power and low-power interconnect resources. A first pass routing step is performance-based, e.g., utilizes a cost function biased towards the high-power interconnect resources. The first routed design is then evaluated to identify non-critical nets in the first routed design that can yield the most power-saving benefit by being retargeted to the low-power interconnect resources. For example, a sorted list of nets can be created in which the identified nets are evaluated based on the capacitance per load pin of each net. A second pass routing step is then performed, e.g., rerouting the nets identified as being non-critical and having the greatest potential power-saving benefit. In some embodiments, the permitted increase in the delay of each rerouted net is bound by the slack of the net as routed in the first routed design.

Programmable logic devices (PLDs) are a well-known type of integrated circuit that can be programmed to perform specified logic functions. One type of PLD, the field programmable gate array (FPGA), typically includes an array of programmable tiles. These programmable tiles can include, for example, input/output blocks (IOBs), configurable logic blocks (CLBs), dedicated random access memory blocks (BRAM), multipliers, digital signal processing blocks (DSPs), processors, clock managers, delay lock loops (DLLs), and so forth.
Each programmable tile typically includes both programmable interconnect and programmable logic. The programmable interconnect typically includes a large number of interconnect lines of varying lengths interconnected by programmable interconnect points (PIPs). The programmable logic implements the logic of a user design using programmable elements that can include, for example, function generators, registers, arithmetic logic, and so forth.
The programmable interconnect and programmable logic are typically programmed by loading a stream of configuration data into internal configuration memory cells that define how the programmable elements are configured. The configuration data can be read from memory (e.g., from an external PROM) or written into the FPGA by an external device. The collective states of the individual memory cells then determine the function of the FPGA.
Another type of PLD is the Complex Programmable Logic Device, or CPLD. A CPLD includes two or more "function blocks" connected together and to input/output (I/O) resources by an interconnect switch matrix. Each function block of the CPLD includes a two-level AND/OR structure similar to those used in Programmable Logic Arrays (PLAs) and Programmable Array Logic (PAL) devices. In CPLDs, configuration data is typically stored on-chip in non-volatile memory. In some CPLDs, configuration data is stored on-chip in non-volatile memory, then downloaded to volatile memory as part of an initial configuration sequence.
For all of these programmable logic devices (PLDs), the functionality of the device is controlled by data bits provided to the device for that purpose. The data bits can be stored in volatile memory (e.g., static memory cells, as in FPGAs and some CPLDs), in non-volatile memory (e.g., FLASH memory, as in some CPLDs), or in any other type of memory cell.
Other PLDs are programmed by applying a processing layer, such as a metal layer, that programmably interconnects the various elements on the device. These PLDs are known as mask programmable devices. PLDs can also be implemented in other ways, e.g., using fuse or antifuse technology. The terms "PLD" and "programmable logic device" include but are not limited to these exemplary devices, as well as encompassing devices that are only partially programmable. For example, one type of PLD includes a combination of hard-coded transistor logic and a programmable switch fabric that programmably interconnects the hard-coded transistor logic.
As noted above, advanced FPGAs can include several different types of programmable logic blocks in the array. For example, FIG. 1 illustrates an FPGA architecture 100 that includes a large number of different programmable tiles including multi-gigabit transceivers (MGTs 101), configurable logic blocks (CLBs 102), random access memory blocks (BRAMs 103), input/output blocks (IOBs 104), configuration and clocking logic (CONFIG/CLOCKS 105), digital signal processing blocks (DSPs 106), specialized input/output blocks (I/O 107) (e.g., configuration ports and clock ports), and other programmable logic 108 such as digital clock managers, analog-to-digital converters, system monitoring logic, and so forth. Some FPGAs also include dedicated processor blocks (PROC 110).
In some FPGAs, each programmable tile includes a programmable interconnect element (INT 111) having standardized connections to and from a corresponding interconnect element in each adjacent tile. Therefore, the programmable interconnect elements taken together implement the programmable interconnect structure for the illustrated FPGA. The programmable interconnect element (INT 111) also includes the connections to and from the programmable logic element within the same tile, as shown by the examples included at the top of FIG. 1.
For example, a CL 102 can include a configurable logic element (CLE 112) that can be programmed to implement user logic plus a single programmable interconnect element (INT 111). A BRAM 103 can include a BRAM logic element (BRL 113) in addition to one or more programmable interconnect elements. Typically, the number of interconnect elements included in a tile depends on the height of the tile. In the pictured embodiment, a BRAM tile has the same height as four CLBs, but other numbers (e.g., five) can also be used. A DSP tile 106 can include a DSP logic element (DSPL 114) in addition to an appropriate number of programmable interconnect elements. An IOB 104 can include, for example, two instances of an input/output logic element (IOL 115) in addition to one instance of the programmable interconnect element (INT 111). As will be clear to those of skill in the art, the actual I/O pads connected, for example, to the I/O logic element 115 are manufactured using metal layered above the various illustrated logic blocks, and typically are not confined to the area of the input/output logic element 115.
In the pictured embodiment, a columnar area near the center of the die (shown shaded in FIG. 1) is used for configuration, clock, and other control logic. Horizontal areas 109 extending from this column are used to distribute the clocks and configuration signals across the breadth of the FPGA.
Some FPGAs utilizing the architecture illustrated in FIG. 1 include additional logic blocks that disrupt the regular columnar structure making up a large part of the FPGA. The additional logic blocks can be programmable blocks and/or dedicated logic. For example, the processor block PROC 110 shown in FIG. 1 spans several columns of CLBs and BRAMs.
Note that FIG. 1 is intended to illustrate only an exemplary FPGA architecture. For example, the numbers of logic blocks in a column, the relative width of the columns, the number and order of columns, the types of logic blocks included in the columns, the relative sizes of the logic blocks, and the interconnect/logic implementations included at the top of FIG. 1 are purely exemplary. For example, in an actual FPGA more than one adjacent column of CLBs is typically included wherever the CLBs appear, to facilitate the efficient implementation of user logic, but the number of adjacent CLB columns varies with the overall size of the FPGA.
In some PLDs, the programmable interconnect is heterogeneous in nature. In other words, at least two different types of routing elements are included in the programmable interconnect. For example, in U.S. Pat. No. 6,930,510, New et al. describe a programmable interconnect structure for a PLD that includes one set of interconnect resources designed for routing high-speed signals, and another set of interconnect resources that consume less power and can be used for routing non-critical signals. Thus, the overall power consumption of the device is reduced by using the high-speed, high-power interconnect resources only for the most critical paths in a user design.
As previously described, the FPGA disclosed by New at al. has a programmable interconnect structure in which the interconnect resources are divided into two groups. A first subset of the interconnect resources are optimized for high speed. A second subset of the interconnect resources are optimized for low power consumption. In some embodiments, the transistors of the first and second subsets have different threshold voltages. Transistors in the first subset, being optimized for speed, have a lower threshold voltage than transistors in the second subset, which are optimized for low power consumption. The difference in threshold voltages can be accomplished using well-known methods such as different doping levels or wells biased to different voltage levels, or by other means. In other embodiments, the interconnect resources include buffers optimized by varying voltage levels, transistor sizes, and so forth.
Therefore, it is clearly desirable to provide methods of routing user designs in programmable ICs having heterogeneous routing architectures, such that the routed designs can take advantage of the heterogeneity to reduce the overall power consumption of the user design.

Methods of routing low-power designs in programmable logic devices having heterogeneous routing architectures


A can (1) has a primary chamber and a secondary chamber in communication through a restricted orifice and its exterior maintained at atmospheric pressure. The can (1) is filled with beer through a filling block (24) from a bowl (8). Prior to filling the can (1) is pressurized through the block (24) with nitrogen gas to greater than atmospheric pressure and subsequently evacuated to atmospheric pressure. Such pressurization and evacuation is repeated sequentially to dilute the atmospheric oxygen content within the primary and secondary chambers. A gas exchange conduit (40) extends between the bowl headspace (12) and the can (1). Conduit (40) has a gas control valve (55) closeable by movement of lever (60). A beer flow valve (37/46) controls flow of beer (9) from the bowl. During nitrogen pressurization of the can (1) the lever (60) is adjusted to maintain valves (55) and (37/46) closed and insure that high pressure gas in the can (1) cannot flow through conduit (40) into the bowl (8).

The present invention relates to a method of and an apparatus for packaging a beverage in a container. More particularly the invention concerns the packaging of a beverage (which may be alcoholic or non-alcoholic) in a sealed container, the atmosphere of which is relieved of oxygen to alleviate deterioration of the beverage by oxidation.
The invention was primarily developed for the packaging of beer such as ale, stout or lager which is sealed in a container to provide a headspace containing nitrogen and/or carbon dioxide at a pressure greater than atmospheric. In the brewing industry it is recognized that the packaging of beer in the presence of atmospheric oxygen can rapidly cause oxidation of the beer and unacceptable deterioration of its desirable characteristics. Consequently precautions are taken to insure that the contamination of beer by oxygen is alleviated during the filling and sealing stages of the container. One well known precaution in a simple beer packaging line is to purge open topped containers (such as light metal cans) of oxygen by flushing the containers with nitrogen gas immediately prior to the container being charged with beer and sealed.
In a beverage package which we have developed and which has met with considerable commercial success, a sealed container has a primary chamber charged with beverage containing gas in solution and a smaller secondary chamber which communicates with the primary chamber by way of a restricted orifice. The secondary chamber contains gas at pressure greater than atmospheric while a headspace is provided in the primary chamber also containing gas at a pressure greater than atmospheric. Upon opening of the container, a pressure differential is created causing gas and/or liquid in the secondary chamber to be ejected by way of the restricted orifice into the beverage in the primary chamber to liberate gas from solution and develop a head or froth on the beverage in the primary chamber. The secondary chamber may be formed integrally with the container or as a hollow insert which is placed within the container. Examples of beverage packages having the aforementioned secondary chamber are disclosed in our European Patent Specification A-227,213 and our British Patent No. 1,266,351.
While the aforementioned flushing with nitrogen gas may purge the primary chamber of atmospheric oxygen, because of the restricted orifice between the primary and secondary chambers such flushing as occurs in a high speed packaging/filling line has negligible effect on the oxygen content in the atmosphere of the secondary chamber. As a consequence elaborate techniques and facilities have been developed for use in a beverage packaging line by which it may be insured that atmospheric oxygen is removed from both the primary and secondary chambers prior to the containers being charged with beverage; examples of these techniques are disclosed in our British Patent Specifications 2,218,078A, 2,218,079A and 2,217,696A.
In the aforementioned prior proposals the container, particularly its primary and secondary chambers, is subjected to a sequence of pressure changes to replace the atmospheric oxygen in the primary and secondary chambers with nitrogen gas. More particularly, the container is sealed to a vacuum source and the primary and secondary chambers initially evacuated; following evacuation of the atmosphere, nitrogen gas is introduced into the primary and secondary chambers of the container and if necessary these steps of evacuation and nitrogen gas introduction can be repeated successively to ensure that nitrogen gas is substituted for the original atmosphere in both the primary and secondary chambers. During evacuation of the container its walls may be subjected to a considerable pressure differential which, in the case of fragile or thin walled containers can cause the container to collapse or implode. Modern packaging containers for beverage are frequently of a structure which, if subjected to evacuation by a vacuum pump, would rapidly collapse at very little pressure differential between the sub-atmospheric pressure in the primary and secondary chambers of the container and atmospheric pressure outside the container--this is especially true of light alloy thin walled cans which are currently favored for the packaging of beverages. To alleviate this problem our aforementioned prior Patent Specifications propose that containers which are liable to collapse during evacuation are located in a pressure chamber by which the interior, that is the primary and secondary chambers, and the exterior of the container are subjected to substantially the same pressure variations during the evacuation and nitrogen gas introduction stages. However, the pressure chambers tend to be relatively bulky and occupy considerable space in a beverage filling line where, typically but not necessarily, there will be forty package locating stations each with a beverage filling head and pressure chamber to accommodate a conventional 500 milliliter beverage can. These stations are spaced along the circumference of a rotary table which carries each can successively through its gas exchange and beverage charging stages. For a given sized rotary table, the space occupied by the pressure chambers restricts the number of can locating stations which can be provided and therefore the rate at which the cans can be processed through the gas exchange and filling stages. Also, of course, the pressure chambers together with appropriate controls for opening and closing those chambers about the respective containers adds significantly to the overall cost of the packaging equipment.
It is an object of the present invention to provide a method of and apparatus for packaging beverage in a container and by which the aforementioned disadvantages associated with the prior proposals for containers of the kind discussed (those having primary and secondary chambers which communicate with each other by way of a restricted orifice) may be alleviated so that an atmosphere having a reduced oxygen content can be provided in a thin walled or fragile container without risking collapse or implosion of the container and without requiring the container to be located in a pressure chamber.

Method of and apparatus for packaging a beverage in a container


A method for securely transporting items in an autonomous vehicle (AV) between travel destinations includes implementing an electronic ledger on an electronic computing device. One or more electronic codes for are stored in the electronic ledger for controlling access to a physical container that can be secured in the AV. One or more destination addresses for the AV are stored in the electronic ledger. After receiving an access code that matches one of the one or more electronic codes, the physical container is secured in the AV. A destination address is obtained from the electronic ledger. The AV is directed to transport the physical container to the destination address.

Items of value often need to be transferred from one physical location to one or more additional physical locations. When items of value are transferred, a reliability of a transport vehicle, a reliability of personnel used to operate the transport vehicle and costs associated with the transfer may need to be considered. In addition, there is a possibility of theft of the items of value and and/or theft of the transport vehicle during the transfer.
Costs involved in transferring items from one physical location to another can include a transportation cost, an insurance cost and a security cost. The transportation cost can include a cost of owning or renting the transport vehicle, maintenance of the transport vehicle and fuel costs for the transport vehicle. The insurance cost can include a cost of insuring the item for damages and theft during transport. The security cost can include a cost of security personnel that may be needed to travel or otherwise accompany the transport vehicle. Other costs are possible.


An image processing method includes: acquiring a video stream of a vehicle by a camera according to a user instruction; obtaining an image corresponding to a frame in the video stream; determining whether the image meets a predetermined criterion by inputting the image into a classification model, the classification model comprising a first convolutional neural network; in response to the image meeting the predetermined criterion, adding at least one of a target box or target segmentation information to the image by inputting the image into a target detection and segmentation model, the at least one of the target box or the target segmentation information corresponding to at least one of a vehicle part or vehicle damage of the vehicle, the target detection and segmentation model comprising a convolutional neural network; and displaying the at least one of the target box or the target segmentation information to the user.

In auto insurance claim settlement scenarios, insurance companies may need to send professional inspection and damage assessment personnel to an accident site to conduct on-site inspections and damage assessments. The insurance companies can provide a vehicle repair plan and a compensation amount, take on-site photos, and keep the damage assessment photos on file for verifying the damage and cost. As the inspection and damage assessment need to be conducted manually, insurance companies have to invest a large amount of human resources and cover expenses associated with professional knowledge training. With respect to the experience of individual users, the claim settlement process involves waiting for the inspector to inspect on site and for the damage assessor to assess damage on the repair site. The process further involves waiting for the damage verifier to verify the damage. The whole claim settlement cycle is lengthy.
With the development of the Internet, other claim settlement solutions have been proposed, where a user takes vehicle damage photos on site and uploads the photos to a server. Damage assessment and claim settlement can then be performed based on the vehicle damage photos according to an algorithm or manually. However, with these solutions, the vehicle damage photos usually satisfy certain requirements. For example, the user is usually required to take vehicle damage photos from the distant to the near. In addition, there are also some requirements on the sharpness, brightness and shooting angles of the photos. In order to meet such requirements, customer service personnel of insurance companies need to communicate with the user by telephone, the internet, or other means, so that they can remotely guide the user to take photos for damage assessment.
In view of the above, more effective solutions are needed for guiding users to take photos for vehicle damage assessment.

This patent is subject to a terminal disclaimer.


Techniques, computer programs and apparatus relating to an integrated calendar and map feature are described. In one implementation, one or more calendar entries are identified in a calendar. A calendar entry includes an associated time and an associated location. A display of a map is provided including a graphical representation indicating a location associated with at least one calendar entry. The location associated with the calendar entry is derived from the calendar entry and included in a request to a map application for the map.

Conventional mobile devices are often dedicated to performing a specific application. For example, a mobile phone provides telephony services; a personal digital assistant (PDA) provides a way to organize address, contacts and notes; a media player plays content; email devices provide email communication, etc. Modern mobile devices can include two or more of these applications. Typically, the two or more applications operate independent of one another, and the device functions as a combination of two or more of the devices described above.

Integrated calendar and map applications in a mobile device


In order to realize the electric contacting of two parallel printed boards, the invention proposes a printed board connector that features coaxial plug modules realized in the form of pin and socket contacts.

1. Field of the Invention
The invention pertains to a printed board connector for electrically contacting two parallel printed boards that comprises at least two plug modules realized in the form of a coaxial contact pair, wherein a pin contact is arranged in one plug module and a socket contact is arranged in the other plug module, and wherein the pin contact or socket contact is centrally held in an insulation element that is surrounded by an electrically conductive sleeve contact.
2. Description of the Related Art
A device of this type is required for mutually contacting two at least approximately parallel printed boards, wherein the design of the contact elements also makes it possible to compensate a misalignment or an offset between the positions of the plug modules and of the printed boards relative to one another to a certain degree.
EP 1 246 304 B1 discloses a coaxial connector, in which a center contact with a spherical head is contacted within a U-shaped spring contact such that it can be turned by a certain angle.
Furthermore, U.S. Pat. No. 5,980,290 discloses an electric coaxial connector with a movable contact, in which, however, only one of the two plug components is arranged in a movable fashion.
Known coaxial connectors of this type for directly contacting two printed boards typically feature two identical and rigid contact modules or even barrel-shaped spacer elements and therefore only able to conditionally compensate a shift or a misalignment between individual modules.

Abstract: For this purpose, it is proposed that the two plug modules have such a design that they can be turned and tilted about their central mating axis within a certain range on the printed board in order to compensate misalignments or deviations between the positions of the printed boards relative to one another.

Abstract: It is furthermore proposed to realize certain distances between the printed boards by means of plug modules of different lengths on the pin side.


A low AC loss electrical conductor includes an electrically conductive core surrounded by a first layer of superconductor filaments. A resistive shell surrounds the first layer and an insulation coating radially encloses the resistive shell.

The invention relates generally to superconducting magnet systems and more particularly to superconducting magnets operating in an alternating current (AC) environment.
In one example, an MR system includes a cold mass comprises a superconducting magnet, a magnet coil support structure, and a helium vessel. Liquid helium contained in the helium vessel provides cooling for the superconducting magnet and maintains the superconducting magnet at a low temperature for superconducting operations, as will be understood by those skilled in the art. The liquid helium maintains the superconducting magnet approximately and/or substantially at the liquid helium temperature of 4.2 Kelvin (K). For thermal isolation, the helium vessel that contains the liquid helium in one example comprises a pressure vessel inside a vacuum vessel.
An MR superconducting magnet typically includes several coils, a set of primary coils that produce a uniform B0 field at the imaging volume, and a set of bucking coils that limit the fringe field of the magnet. These coils are wound with superconductors such as NbTi or Nb3Sn conductors. The magnet is cooled down to liquid helium temperature (4.2 K) so that the conductors are operated at their superconducting state. The heat loads of the magnet, such as that produced by the radiation and conduction from the environment, are removed by either the boil-off of liquid helium in an "open system" or by a 4 K cryocooler in a "closed system". The magnet is typically placed in a cryostat to minimize its heat loads since the replacement of liquid helium is expensive and since the cooling power of a cryocooler is limited. If the coils are exposed to an AC field such as an AC field generated by gradient coils of the MR system, AC losses are generated in the superconductors. That is, when superconducting coils are exposed to an AC field, hysteresis loss and eddy currents are induced therein that contribute to AC losses, which can raise the conductor temperatures and potentially cause a quench. The AC losses also add to the total heat load for the refrigeration system. A rise in heat load requires additional cryogenic refrigeration power, which increases operating costs.
It would therefore be desirable to have an apparatus configured to reduce AC losses caused by hysteresis loss and eddy currents induced in superconducting magnet coils.

Low AC loss superconductor for a superconducting magnet and method of making same


In accordance with certain disclosed embodiments of the present invention, there is provided an assay test device for determining whether a fluid under test contains a certain substance, wherein the device includes a test strip disposed at least partially within a housing for receiving the fluid under test. A sensor mounted on the housing detects the certain substance in the fluid under test received on the test strip to generate an electrical signal indicative of the amount of the substance detected. A processor responds to the signal for determining whether or not the fluid under test contains a predetermined quantity of the certain substance to generate an electrical signal. A display mounted on the housing responds to the output signal to indicate the presence or absence of a predetermined quantity of the certain substance contained within the fluid under test.

There is no admission that the background art disclosed in this section legally constitutes prior art.
Assay tests have been employed to analyze test samples such as urine samples to determine whether or not they contain substances such as HCG indicating pregnancy, drugs of abuse, or other.
For example, reference may be made to the following United States patents, each of which is incorporated herein by reference:
PATENT NO.INVENTORISSUE DATE4,033,723Givner, et al.Jul. 05, 19774,123,509Banik, et al.Oct. 31, 19784,348,207CappelSep. 07, 19824,450,239ChattertonMay 22, 19844,700,711CarlsonOct. 20, 19875,182,216Clayton, et al.Jan. 29, 19935,580,794Allen, et al.Dec. 3, 19965,656,503May, et al.Aug. 12, 19975,786,220Pronovost, et al.Jul. 28, 19985,837,546Allen, et al.Nov. 17, 19986,063,026Schauss, et al.May 16, 20006,150,178Cesarczyk, et al.Nov. 21, 20006,235,241B1Catt, et al.May 22, 2001
Test strips, as disclosed in one or more of the foregoing patents, are employed to receive a test sample such as a urine sample for performing an assay test. For example, a pregnancy test strip has been used to collect a urine sample to react with a reagent to produce a visible line such as a line having a pink/purple color. It is sometimes difficult to make a subjective determination as to the intensity of the color of the line relative to a comparison line. Thus, false positive indications are sometimes possible.
In an attempt to help interpret the results of such assay test, the U.S. Pat. No. 6,235,241B1 discloses a test strip disposed within a casing or housing, and includes a light source with diffusers to illuminate the test strip to help the user to interpret the results of a test. Light sensors on the other side of the test strip detect the light shining through the test strip. However, such a device is complex in its construction, and thus relatively expensive to manufacture.
For the purpose of making a relatively inexpensive assay test device, which can be for single use only, as disclosed in U.S. Pat. Nos. 5,580,794 and 5,873,546, a disposable device includes a test membrane containing a reagent for receiving a liquid test sample. A set of electrodes detects the presence of movement of the sample liquid to activate the device electrically to cause sensors to sense the results of the chemical reaction of the reagent with the test sample. In this regard, as the liquid sample moves toward the electrodes, the reaction is occurring and the results are sensed once the liquid reaches the electrodes. Alternatively, the device may be activated electrically by closing a switch when it is removed from its pouch, and the reaction results are sensed after a specified time.
However, when the electrodes are used, the reaction time may be dependent on the length of time it takes for the movement of the liquid sample along the membrane. Thus, the reaction time may not be precisely controlled and repeatable, and thus accuracy may be adversely affected. When the alternative approach of sensing the reaction results after initially turning on the device, following a time delay, the reaction time is even less precisely controlled, because there is little or no control over when the sample is introduced to the membrane following the activation of the device.
Therefore, it would he highly desirable to have a new and improved testing device and method of using it, which are relatively more accurate in the determination of the test results, while at the same time being relatively inexpensive to manufacture and to use. Thus, such a device and method may, if desired, be employed for a single use, and yet be relatively accurate in its use.

Assay test device and method of making same


A method for diagnosing charging state may include a diagnostic trouble code generation step of generating a diagnostic trouble code (DTC) when the state for charging a battery from an alternator is abnormal in the state in which the alternator is operating to charge the battery while a vehicle is traveling, and then storing diagnostic trouble code in an ECU (Electronic Control Unit), and a diagnostic trouble code release step of deleting the diagnostic trouble code in the ECU when the state for charging the battery from the alternator is returned to be normal.

Field of the Invention
An exemplary embodiment of the present invention relates to a method and system for diagnosing charging state that diagnoses one of the causes of starting off, and particularly, to the method and system for diagnosing charging state to facilitate an attribution and a maintenance of a starting off when the starting off occurs due to a charging defect, in order to determine whether the starting off is caused by the charging defect or not, by storing the state in which the charging state from the alternator is abnormal in the low battery voltage state as a diagnostic trouble code.
Description of Related Art
In the ECU (Electronic Control Unit) of a vehicle, an abnormal state of each parts of the vehicle is stored as a diagnostic trouble code (DTC; Diagnostic Trouble Code), which is used for checking of the vehicle and repairing.
For example, the diagnostic trouble cause of the vehicle may be readily grasped by checking the diagnostic trouble code via a scanner during maintenance.
However, it was not easy to act the trouble for some defect conditions of the vehicle, because it could not be recorded by the diagnostic trouble code.
As an example, there was a trouble that the case where the charging state from the alternator is not normal in the low battery voltage state, is not stored as a diagnostic trouble code.
As described above, if the charging state from the alternator is not normal in the low battery voltage state, the voltage of the power supplied to each part of the vehicle is lowered to less than the reset voltage of the ECU (Electronic Control Unit) and the various actuators of the vehicle so that the ECU and the actuator did not operate properly, as a result, it could not save it as a diagnostic trouble code.
In addition, as described above, when the battery voltage is low and the charging state from the alternator is defective, the sufficient power to maintain the starting of the vehicle is not supplied so that a starting off sometimes occurs. However, as described above, the state where the battery is low and the charging state from the alternator is defective, is not recorded as a diagnostic trouble code, thereby causing the problem in which the cause of the starting off could not be accurately grasped.

Method and system for diagnosing charging state


An image processing apparatus configured to print a sheet to instruct outputting an image includes an analysis unit configured to analyze an image stored in an image storage unit, a conversion unit configured to convert a size of the image according to a result of the analysis performed by the analysis unit, and a printing unit configured to print the image converted by the conversion unit onto the sheet.

1. Field of the Invention
The present invention relates to an image processing apparatus configured to produce and read an index sheet and a control method therefor.
2. Description of the Related Art
Recently, digital input devices such as a digital cameras and image scanners, and digital output devices such as inkjet printers have been widely used. A user can perform image processing using these devices in conjunction with a personal computer (PC).
Multifunction peripherals (MFP), in which a scanner and a printer are integrated, have also been widely used. With the MFP, image processing, such as copying a photograph, can be performed without using a PC. Most home-use MFPs have a small size operation unit or a small number of keys, and a dedicated viewer is required to select an image. Therefore, an image processing operation is more difficult on an MFP as compared with a PC.
In a conventional method for printing image data stored in an external memory storage device, such as a memory card, without using a PC, a MFP including an apparatus to read image data from the external storage device is used. In this method, an index sheet is typically used to navigate through the image data.
FIG. 10 illustrates a conventional index sheet IS1. On the conventional index sheet IS1, index images, which are candidate images to be printed, are collectively printed. A mark field is provided to each of the printed index images. A mark field is also provided for designating print settings. An MFP prints the index sheet IS1. Here, an index image refers to a reduced image of the main image stored in the memory card.
A user marks the mark field for the index sheet IS1 to designate the printing settings and an image to be printed. This method is similar to a method for making an additional copy of a photograph, and therefore, is easy for a user to intuitively understand. Then, the reading unit of the MFP reads the index sheet filled in by the user, and the image data stored in the external storage device is printed according to the index sheet filled in by the user.
According to this conventional method, instead of the complicated photograph printing operation performed through an operation panel, the photograph can be easily printed without using a PC.
For a method for printing a photograph, Japanese Patent Application Laid-Open No. 09-281605 discusses an image processing apparatus which can automatically detect the number of object persons existing in an image and makes additional copies of the photograph in the detected number of object persons.
Japanese Patent Application Laid-Open No. 2005-286737 also discusses an image processing apparatus including a function for detecting the number of object persons and causing a user to select a layout sample of a photograph sticker according to the detected number of object persons.
In the case of the above-described conventional index sheet, when, for example, a photograph containing a group of object persons or a commemorative photograph, in which many persons are present, is used for an index image, each person is too small to be recognized.
Thus, good photographs can be selected only after all the candidate photographs are once printed to confirm facial expressions of the persons. Accordingly, convenience of a user becomes low, and an ink, a sheet, and time are wasted.
In the above-described conventional method, in the case of recording photographs according to the number of photographed persons, when a photograph shows a group of fifty persons and one additional copy of the photograph is desired to be made, for example, fifty additional copies are printed, which also results in wasting the ink, the sheet, and time.
In the method discussed in Japanese Patent Application Laid-Open No. 2005-286737, in selecting a layout of a photograph sticker, a desired layout can be easily selected out of a plurality of layouts considering the number of object persons. However, the persons in a photograph cannot be easily recognized when a large number of object persons are taken in a photograph.

Image processing apparatus and control method for printing image sized according to determined face area


A method of operation of a display system includes: determining a correction profile for adjusting an intended image based on a viewing aide; and generating an adjusted output image based on the correction profile for displaying on a device and for perceiving the intended image through the viewing aide.

Modern consumer and industrial electronics, especially devices such as graphical display systems, televisions, projectors, cellular phones, portable digital assistants, and combination devices, are providing increasing levels of functionality to support modern life including three-dimensional display services. Research and development in the existing technologies can take a myriad of different directions.
As users adopt the advancements in devices, new and old usage begin to take advantage of this new technology. Similarly, display systems and service providers are continually making improvement in the user's experience to be competitive. However, the new technology has also brought new challenges that degrade the viewing experience in different ways.
The desire to provide accurate and clear visual depictions in electronic devices has served as a motivating factor in the innovation of display devices. This is especially true with advancements in high definition displays and three dimensional displays.
Thus, a need still remains for a three-dimensional display system with display enhancement mechanism to display three-dimensional images. In view of the ever-increasing commercial competitive pressures, along with growing consumer expectations and the diminishing opportunities for meaningful product differentiation in the marketplace, it is increasingly critical that answers be found to these problems. Additionally, the need to reduce costs, improve efficiencies and performance, and meet competitive pressures adds an even greater urgency to the critical necessity for finding answers to these problems.
Solutions to these problems have been long sought but prior developments have not taught or suggested any solutions and, thus, solutions to these problems have long eluded those skilled in the art.

Display system with display adjustment mechanism for viewing aide and method of operation thereof


A new and distinct cultivar of Lavandula plant named ‘Pink Summer’, characterized by its compact, upright and somewhat outwardly spreading plant habit; freely branching growth habit; dense and bushy plant form; early and freely flowering habit; purple-colored flowers with light violet-colored terminal flower bracts; flowers arranged in compact verticillasters on crowded spikes; and good garden performance.

The present invention relates to a new and distinct cultivar of Lavandula plant, botanically known as Lavandula stoechas and hereinafter referred to by the name 'Pink Summer'.
The new Lavandula plant is a product of a planned breeding program conducted by the Inventor in Odense, Denmark. The objective of the breeding program was to develop new compact Lavandula plants with attractive plant form and flower coloration.
The new Lavandula plant originated from a cross-pollination made by the Inventor in 2004 of two unnamed proprietary selections of Lavandula stoechas, not patented. The new Lavandula plant was discovered and selected by the Inventor in 2005 as a single flowering plant within the progeny of the stated cross-pollination in a controlled outdoor nursery environment in Odense, Denmark.
Asexual reproduction of the new Lavandula by terminal cuttings in a controlled greenhouse environment in Odense, Denmark since 2006 has shown that the unique features of this new Lavandula plant are stable and reproduced true to type in successive generations.


A process for particulate agglomeration (i.e., pelletizing) and the product produced (i.e., pellets) by such processes are disclosed. The process generally comprises a process of agglomerating particulate material, said process comprising commingling said particulate material with a moistening effective amount of water, a binding effective amount of polymer and a binding effective amount of weak acid to produce a mixture and forming said mixture into agglomerates.

The present invention relates to a process for agglomerating particulate material and the products produced by such processes. The processes are particularly useful for agglomerating metallic ores and, most particularly, iron ore.
Processes for agglomerating particles, especially metallic particles, are known in the art. Such processes are described more fully in, e.g. Canadian Patent No. 890 342, issued Jan. 11, 1972. As disclosed in Canadian Patent No. 890 342, it is well known to mechanically agitate water-wet particles to promote the operation of cohesive forces which produces larger agglomerates of the particulate solids. The mechanical agitation may be produced by rolling or cascading motion as is achieved in balling drums, discs and cones. Another agglomeration method utilizes agitation induced by paddle type agitators, such as in pug mills.
As agglomeration proceeds, aggregates in the form of pellets, balls, or granules are formed. As the agglomerates are agitated, e.g. rolled or tumbled, particles are added to their surface as a continuous film. The growth of larger agglomerates is also attributed to coalescence of smaller particles and agglomerates. Sometimes the agglomerates are dusted with finely divided dry particles to minimize sticking problems or sprayed with liquid, e.g. water, if the mixture becomes too dry. When their size is sufficient, the agglomerates are removed from the agitating mechanism for further processing such as induration by heating to low temperatures and sintering at higher temperatures depending upon the utilitarian nature of the starting materials.
International Patent Publication WO 88/00232 discloses a binder for fuels (especially coal) comprised of guar gum. A small amount of citric acid may be optionally added to adjust the pH.
European Patent Application Publication No. 0 376 713 discloses a process for making pellets of particulate metal ore, particularly iron ore. The process comprises mixing a water-soluble polymer with the particulate metal ore and water and pelletizing the mixture. The water-soluble polymer may be of any typical type, e.g., natural, modified natural or synthetic. The mixture may optionally comprise a pelletizing aid which may be sodium citrate.
U.S. Pat. No. 4,288,245 discloses pelletization of metallic ores, especially iron ore, with carboxymethyl cellulose and the salt of a weak acid.
Australian Patent Specification 46544/85 discloses a pelletizing process for iron ore employing hydroxymethyl cellulose and an inorganic salt (e.g. sodium carbonate). Guar gum may be used as a carrier.
European Patent Application Publication No. 0 203 855 discloses a binder comprised of a polymer (especially a polyacrylamide-based polymer) and an inorganic salt such as sodium carbonate. According to this disclosure, the polymer-inorganic salt binder may be used for agglomeration of both xe2x80x9cmineral orexe2x80x9d and xe2x80x9ccoal dust and nonmetallic materialsxe2x80x9d.
U.S. Pat. Nos. 4,863,512 and 4,919,711 disclose iron ore binder compositions comprised of alkali metal salts of carboxymethyl cellulose and/or carboxymethyl hydroxyethyl cellulose and sodium tripolyphosphate. Incidentally, these U.S. patents mention that their binder compositions may contain additional polysaccharides, such as guar and hydroxypropyl guar and inorganic salts, such as sodium citrate and sodium carbonate.
Abstract 22,244Q, 1968, abstracting the U.S.S.R. inventor certificate RU 205982, published July, 1968, discloses a method of preparing mixtures of powders for the production of sintered ferrites. In that process boric acid and sodium carboxymethyl-cellulose are solubilized. Barium ferrite powder is mixed with 6% of the solution, compressed, dried and sintered.
Even in the face of such technical knowledge, there remains a need for economical binders with improved properties.
In one embodiment, the current invention is a process of agglomerating particulate material, said process comprising commingling said particulate material with a moistening effective amount of water, a binding effective amount of polymer and a binding effective amount of weak acid to produce a mixture and forming said mixture into agglomerates.
In another embodiment, the current invention is a process of agglomerating particulate material, said process comprising commingling said particulate material with (1) a moistening effective amount of water, (2) a binding effective amount of a polymer selected from the group consisting of guar, guar derivatives, starch, modified starch, starch derivatives, alginates, pectins and mixtures thereof and (3) a binding effective amount of the salt of a weak acid to produce a mixture and forming said mixture into agglomerates.
In yet another embodiment, the current invention is pellets comprised of particulate material, a binding effective amount of polymer and a binding effective amount of a weak acid. Optionally, the pellets may be comprised of a polymer selected from the group consisting of guar, guar derivatives, starch, modified starch, starch derivatives, alginates, pectins, and mixtures thereof and the salt of a weak acid.
Polymers. The polymers useful in the present invention may be (1) a water-soluble natural polymer, such as guar gum or starch, (2) a modified natural polymer, such as guar derivatives (e.g. hydroxypropyl guar, carboxymethyl guar), modified starch (e.g. anionic starch, cationic starch), starch derivatives (e.g. dextrin) and cellulose derivatives (e.g. hydroxyethyl cellulose, carboxymethyl cellulose, hydroxypropyl cellulose, methyl cellulose), and/or (3) a synthetic polymer (e.g. polyacrylamides, polyacrylates, polyethylene oxides). Such polymers may be used alone or as combinations of two or more different polymers.
The binding effective amount of polymer will vary depending upon numerous factors known to the skilled artisan. Such factors include, but are not limited to, the type of particulate material to be agglomerated or pelletized, the moisture content of the particulate material, particle size, the agglomeration equipment utilized, and the desired properties of the final product, e.g. dry strength (crush), drop number, pellet size and smoothness. Though not limiting, a binding effective amount of polymer will typically be in the range of about 10 to about 99 wt. % and about 40 to about 95 wt. % based on total binder weight.
Acids and Their Salts. The acids useful in the current invention are weak organic or inorganic acids, having degrees of acidity such that their pK is higher than about 3. The pK is defined here as pK=xe2x88x92log K, where K is the dissociation constant of the acid or already dissociated acids at 25xc2x0 C. in water (see C. D. Hodgeman, Handbook of Chemistry and Physics, 30th Ed., 1947, p. 1425). As non-limiting examples of such acids may be mentioned: acetic acid, benzoic acid, lactic acid, propionic acid, tartaric acid, succinic acid, citric acid, nitrous acid, boric acid, carbonic acid, fumaric acid, malic acid and the like.
In certain embodiments of the current invention, use is made from the salts derived from such acids and, for example, alkali metals (e.g. sodium, potassium and lithium,) ammonia, etc. Particularly preferred salts are those derived from alkali metal and citric and or carbonic acid, such as carbonates and bicarbonates and citrates of potassium and sodium. The salts contemplated herein may be used in their hydrated or anhydrous forms. Specific salts of interest are sodium citrate, sodium carbonate, sodium tartrate, sodium bicarbonate, sodium stearate, sodium benzoate, sodium oxalate, sodium acetate, sodium glycolate and the corresponding ammonium, potassium, calcium and magnesium salts of these acids.
A binding effective amount of weak acid or salt of a weak acid, as with the polymer, will depend on many factors well known to the skilled artisan. However, generally, a binding effective amount of weak acid or salt of a weak acid will be about 1 to about 90 wt. % acid and preferably about 5 to about 60 wt. % based on total binder weight.
Binder Addition. The amount of binder, comprised of polymer and weak acid or salt of a weak acid, added to particulate material to be agglomerated will depend on many factors as discussed above. However, a typically effective amount of binder added is 0.01 to about 5.0 wt. %, and preferably about 0.03 to about 0.3 wt. %, of the agglomerating mixture.
The binder may be added in any of the typical physical forms as known by the skilled artisan, e.g. dry, liquid, emulsion, dispersion, etc.
Water. The initial moisture content of the particulate material, polymer and acid or weak acid salt mixture will also depend on many factors known to the skilled artisan. As non-limiting ranges, generally, the water content of such mixture should be about 4 to about 30 wt. % based on the weight of dry particulate matter and most preferably about 7 to about 12 wt. %.

Process for agglomerating particulate material