An apparatus for combustion condition diagnosis has an ionic current detecting circuit for measuring a voltage at the secondary side of the ignition coil of an engine during a plurality of time periods during one operation cycle including a period in which an internal pressure of a cylinder of the engine becomes maximum, under a normal combustion condition. A window generation circuit is provided for establishing the time periods, an integration circuit is provided for integration processing of the measured voltage during each time period, a ROM stores a list indicating combustion condition corresponding to the integrated value for the each time period, and a CPU diagnoses the combustion condition based on the integrated value for the each time period and the list of combustion conditions, in order to decrease erroneous judgement and perform more adequate combustion condition diagnosis.

The present invention relates to a method and apparatus for diagnosis of a combustion condition in an internal combustion engine and a control apparatus provided therewith.
An example of a conventional apparatus for combustion diagnosis is disclosed in JP-A-2-104978 (1990).
In accordance with the known apparatus for combustion diagnosis, judgement as to whether misfire is occurring or not is performed by detecting an electric current after a constant voltage is supplied to an ignition plug subsequent to sparking of the ignition plug. When the ignition plug sparks, the atmosphere around the ignition plug is ionized; and, accordingly, if a voltage is applied to the ignition plug, an electric current, that is an ionic current, flows between the contacts of the ignition plug. The ionic current is measured for a predetermined period as a sample, and the sample is compared with a predetermined current level for judging whether misfire is occurring or not. However, in accordance with the prior art, the diagnosis of the combustion condition is performed by comparison of an ionic current, which is measured at only one sampling time, with a predetermined current level, and, consequently, the prior art has a problem that judgement errors occur relatively frequently.

Combustion condition diagnosis utilizing multiple sampling of ionic current


Methods of promoting tolerance and inhibiting NK cell mediated attack in a human recipient to a swine graft are disclosed The methods include introducing into the recipient a swine hematopoietic stem cell which has been transformed with a transgene encoding a human MHC class I protein that inhibits recipient NK cell mediated attack.

The invention relates to the field of organ transplantation.
Technical advances in allogeneic organ transplantation and the availability of nonspecific immunosuppressive agents have revolutionized the field of organ transplantation. This progress has, however, resulted in a shortage of essential organs of suitable size and match.
The shortage of allograft-organs has led to an increased interest in xenogeneic transplantation. It was demonstrated more than twenty-five years ago that transplants from chimpanzee to man could provide long-term life-supporting function. However, the use of non-human primates as an organ source is of limited applicability. Many primate species are scarce and protected, and those that are more plentiful, such as the baboon, often do not grow to a size which allows the use of their organs in adults. Moreover, in some cultures, the use of primates as a source of organs is ethically unacceptable.
Some of these difficulties could be resolved by use of ungulate organs, especially pig organs. Pigs are domesticated, easy to breed, have large litters, and grow rapidly to the size which allow the use of their organs in the very largest human beings. In addition, pig and man have many anatomical and physiological similarities. However, transplantation of a pig organ into a human results in a vigorous rejection of the graft-organ.
In general, the invention features, a genetically engineered swine cell, e.g., a cultured swine cell, a retrovirally transformed swine cell, or a cell derived from a transgenic swine. The cell includes a transgene which encodes a xenogeneic, e.g., a human, class I MHC protein, e.g., an HLA A, B, C or G gene.
In preferred embodiments the transgene includes an xcex1 subunit, e.g., an HLA class I gene, e.g., an HLA C gene.
Where the transgene includes an HLA C gene, the allele, by way of example, can be any Cw1, Cw2, Cw3, Cw4, Cw5, Cw6, Cw7, Cw8, Cw9, Cw7/8v, or Cw10 allele. As is discussed below, alleles of HLA class I genes can often be classed into reactivity groups wherein an allele from a reactivity group can confer protection against NK cells specific to other alleles in the reactivity group. Thus, in preferred embodiments, the transgene includes an allele which is a member of a reactivity group, e.g., a Group 1 allele, e.g., any of an HLA C Cw2, Cw4, Cw5, or Cw6 allele, or a Group 2 allele, e.g., any of an HLA C Cw1, Cw3, Cw7, or Cw8 allele. In other preferred embodiments the allele has: an Asn at residue 77 and a Lys at residue 80; or a Ser at residue 77 and an Asn at residue 80.
In preferred embodiments the transgene includes an HLA A gene. In other preferred embodiments the transgene includes an HLA B gene.
In other preferred embodiments the transgene includes an HLA G gene, e.g, any of alleles I-IV of HLA G.
In preferred embodiments: the cell includes a second transgene which includes a class I MHC protein. In preferred embodiments the second transgene includes an HLA class I gene, e.g., an HLA A, B, C or G gene. In preferred embodiments the first transgene includes an allele from a first reactivity group and the second transgene includes an allele from a second reactivity group. For example, the first transgene includes a Group 1 allele, e.g., any of an HLA C Cw2, Cw4, Cw5, or Cw6 allele, and the second transgene includes a Group 2 allele, e.g., any of an HLA C Cw1, Cw3, Cw7, or Cw8 allele. In preferred embodiments the first transgene encodes an allele which has an Asn at residue 77 and a Lys at residue 80 and the second transgene encodes an allele which has a Ser at residue 77 and an Asn at residue 80. In other preferred embodiments the second transgene encodes a human xcex2 subunit, e.g., a xcex2-2 microglobulin gene.
In preferred embodiments the transgene includes a chimeric class I gene, e.g., a chimeric HLA A, B, C, or G gene. The chimeric transgene can include a first portion derived from a first allele of a gene encoding a class I protein and a second portion derived from a second allele of the gene encoding the class I protein. In other embodiments, the class I gene is a synthetic sequence selected for the ability to produce a protein which protects a target cell from attack from more than one class of NK cells. In preferred embodiments the transgene includes a gene, e.g., a chimeric or mutated HLA C gene, which confers protection to more than one class of NK cells, e.g., an allele of HLA C having serine at position 77 and lysine at position 80, see e.g., Biassoni, 1995, J. Exp. Med. Vol. 182: 605-609, hereby incorporated by reference. See also Moretta et al., 1996, Ann. Rev. Immunol. 14: 619-648, hereby incorporated by reference, which together with the disclosure herein, provides guidance for altering critical residues in the HLA C genes.
In yet other preferred embodiments the genetically engineered swine cell is: a swine hematopoietic stem cell, e.g., a cord blood hematopoietic stem cell, a bone marrow hematopoietic stem cell, or a fetal or neonatal liver or spleen hematopoietic stem cell; derived from differentiated blood cells, e.g. a myeloid cell, such as a megakaryocyte, monocyte, granulocyte, or an eosinophil; an erythroid cell, such as a red blood cell, e.g. a lymphoid cell, such as B lymphocytes and T lymphocytes; derived from a pluripotent hematopoietic stem cell, e.g. a hematopoietic precursor, e.g. a burst-forming units-erythroid (BFU-E), a colony forming unit-erythroid (CFU-E), a colony forming unit-megakaryocyte (CFU-Meg), a colony forming unit-granulocyte-monocyte (CFU-GM), a colony forming unit-eosinophil (CFU-Eo), or a colony forming unit-granulocyte-erythrocyte-megakaryocyte-monocyte (CFU-GEMM); a swine cell other than a hematopoietic stem cell, or other blood cell; a swine thymic cell, e.g., a swine thymic stromal cell; a bone marrow stromal cell; a swine liver cell; a swine kidney cell; a swine epithelial cell; a swine hematopoietic progenitor cell; a swine muscle cell, e.g., a heart cell; an endothelial cell; or a dendritic cell or precursor thereof.
In yet other preferred embodiments the cell is: isolated or derived from cultured cells, e.g., a primary culture, e.g., a primary cell culture of hematopoietic stem cells; isolated or derived from a transgenic animal.
In yet other preferred embodiments: the swine cell is homozygous for the transgene; the swine cell is heterozygous for the transgene; the swine cell is homozygous for the transgene (heterozygous transgenic swine can be bred to produce offspring that are homozygous for the transgene); the swine cell includes two or more transgenes.
In yet other preferred embodiments the cell includes a one or more, or all of, of a transgene which encodes an HLA A gene, a transgene which encodes an HLA B gene, a transgene which encodes an HLA C gene, and a transgene which encodes an HLA G gene.
In another aspect, the invention features a nucleic acid, e.g., a transgene, including a swine promoter operably linked to a xenogeneic, e.g., human, nucleic acid which encodes a class I MHC protein. The swine promoter can be, e.g., a swine hematopoietic epithelial gene promoter, or a heterologous inducible or developmentally regulated promoter.
In preferred embodiments the nucleic acid includes, e.g., a gene which encodes an a subunit, e.g., an HLA class I gene, e.g., an HLA A, B, C, or G gene, or a gene which encodes a human xcex2 subunit, e.g., a xcex2-2 microglobulin gene
Where the nucleic acid includes an HLA C gene, the allele, by way of example, can be any Cw1, Cw2, Cw3, Cw4, Cw5, Cw6, Cw7, Cw8, Cw9, Cw7/8v, or Cw10 allele. In preferred embodiments the nucleic acid encodes an allele which is a member of a reactivity group, e.g., a Group 1 allele, e.g., any of an HLA C Cw2, Cw4, Cw5, or Cw6 allele, or a Group 2 allele, e.g., any of an HLA C Cw1, Cw3, Cw7, or Cw8 allele. In other preferred embodiments the allele has an Asn at residue 77 and a Lys at residue 80 or a Ser at residue 77 and an Asn at residue 80.
In preferred embodiments, the nucleic acid or transgene further includes transcriptional regulatory sequences, e.g. a tissue-specific promoter, e.g., a hematopoietic specific promoter, operably linked to the non-swine gene sequence.
In preferred embodiments the nucleic acid or transgene encodes a chimeric class I protein, e.g., a chimeric HLA A, B, C, or G protein. The chimeric transgene can include a first portion derived from a first allele of a gene encoding a class I protein and a second portion derived from a second allele of the gene encoding the class I protein. In other embodiments, the class I gene is a synthetic sequence selected for the ability to produce a protein which protects a target cell from attack from more than one class of NK cells. In preferred embodiments the transgene is a chimeric or mutated HLA C gene which confers protection to more than one class of NK cells, e.g., an allele of HLA C having serine at position 77 and lysine at position 80.
In another aspect, the invention features, a transgenic swine having cells which include a xenogeneic, e.g., a human, nucleic acid, e.g., a transgene which encodes an HLA class I protein. In preferred embodiments the transgene can include a nucleic acid which encodes an a subunit, e.g., an HLA class I gene, e.g., one or more of. In other preferred embodiments the transgene includes a nucleic acid which encodes a human xcex2 subunit, e.g. xcex2-2 microglobulin gene.
In preferred embodiments in which the transgene includes an HLA C gene, the allele, by way of example, can be any Cw1, Cw2, Cw3, Cw4, Cw5, Cw6, Cw7, Cw8, Cw9, Cw7/8v, or Cw10 allele. In preferred embodiments the transgene includes an allele which is a member of a reactivity group, e.g., a Group 1 allele, e.g., any of an HLA C Cw2, Cw4, Cw5, or Cw6 allele, or a Group 2 allele, e.g., any of an HLA C Cw1, Cw3, Cw7, or Cw8 allele. In other preferred embodiments the allele has an Asn at residue 77 and a Lys at residue 80 or a Ser at residue 77 and an Asn at residue 80.
In preferred embodiments the transgene encodes a chimeric class I protein, e.g., chimeric HLA A, B, C, or G gene. The chimeric transgene can include a first portion derived from a first allele of a gene encoding a class I protein and a second portion derived from a second allele of the gene encoding the class I protein. In other embodiments, the class I gene is a synthetic sequence selected for the ability to produce a protein which protects a target cell from attack from more than one class of NK cells. In preferred embodiments the transgene includes a gene, e.g., a chimeric or mutated HLA C gene, which confers protection to more than one class of NK cells, e.g., an allele of HLA C having serine at position 77 and lysine at position 80.
In preferred embodiments: the transgenic swine includes a second transgene which encodes a class I MHC protein. In preferred embodiments the transgene includes a gene which encodes a human xcex2 subunit, e.g., a xcex2-2 microglobulin gene. In other preferred embodiments the second transgene includes an HLA class I gene, e.g., an HLA A, B, C, or G gene. In preferred embodiments the first transgene includes an allele from a first reactivity group and the second transgene includes an allele from a second reactivity group. In preferred embodiments the transgene includes an allele which is a member of a reactivity group, e.g., a Group 1 allele, e.g., any of an HLA C Cw2, Cw4, Cw5, or Cw6 allele, or a Group 2 allele, e.g., any of an HLA C Cw1, Cw3, Cw7, or Cw8 allele. In other preferred embodiments the first transgene encodes an HLA C allele which has an Asn at residue 77 and a Lys at residue 80 and the second transgene encodes an HLA C allele which has a Ser at residue 77 and an Asn at residue 80.
In yet other preferred embodiments: the transgenic swine cell is hemizygous for the transgene; the transgenic swine cell is hemizygous for the transgene; the transgenic swine is heterozygous for the transgene; the transgenic swine is homozygous for the transgene (heterozygous transgenic swine can be bred to produce offspring that are homozygous for the transgene); the transgenic swine includes two or more transgenes.
In yet other preferred embodiments the transgenic swine includes a one or more, or all, of a transgene which encodes an HLA A gene, a transgene which encodes an HLA B gene, a transgene which encodes an HLA C gene, a transgene which encodes an HLA G gene.
Transgenic swine (or swine cells) of the invention can be used as a source for xe2x80x9chumanizedxe2x80x9d tissue for grafting into a human recipient, e.g., hematopoietic cells or other tissues or organs.
In another aspect, the invention features, a swine organ or a swine tissue, having cells which include a xenogeneic, e.g., a human, nucleic acid, e.g., a transgene which encodes an HLA class I protein. In preferred embodiments the transgene can include a nucleic acid which encodes an a subunit, e.g., an HLA class I gene, e.g., an HLA A, B, C, or G gene. In other preferred embodiments the transgene includes a nucleic acid which encodes a human xcex2 subunit, e.g. xcex2-2 microglobulin gene.
In preferred embodiments the organ is a heart, lung, kidney, pancreas, or liver.
In preferred embodiments the tissue is: thymic tissue; islet cells or islets; stem cells; bone marrow; endothelial cells; skin; or vascular tissue.
In preferred embodiments in which the transgene includes an HLA C gene, the allele, by way of example, can be any Cw1, Cw2, Cw3, Cw4, Cw5, Cw6, Cw7, Cw8, Cw9, Cw7/8v, or Cw10 allele. In preferred embodiments the transgene includes an allele which is a member of a reactivity group, e.g., a Group 1 allele, e.g., any of an HLA C Cw2, Cw4, Cw5, or Cw6 allele, or a Group 2 allele, e.g., any of an HLA C Cw1, Cw3, Cw7, or Cw8 allele. In other preferred embodiments the allele has an Asn at residue 77 and a Lys at residue 80 or a Ser at residue 77 and an Asn at residue 80.
In preferred embodiments the transgene encodes a chimeric class I protein, e.g., chimeric HLA A, B, C, or G gene. The chimeric transgene can include a first portion derived from a first allele of a gene encoding a class I protein and a second portion derived from a second allele of the gene encoding the class I protein. In other embodiments, the class I gene is a synthetic sequence selected for the ability to produce a protein which protects a target cell from attack from more than one class of NK cells. In preferred embodiments the transgene includes a gene, e.g., a chimeric or mutated HLA C gene, which confers protection to more than one class of NK cells, e.g., an allele of HLA C having serine at position 77 and lysine at position 80.
In yet other preferred embodiments: the transgenic swine organ or tissue includes: a cell which is hemizygous for the transgene; a cell which is hemizygous for the transgene; a cell which is heterozygous for the transgene; a cell which is homozygous for the transgene (heterozygous transgenic swine can be bred to produce offspring that are homozygous for the transgene); a cell which includes two or more transgenes.
In preferred embodiments: the swine organ or tissue includes cells which include a second transgene which encodes a class I MHC protein. In preferred embodiments the second transgene includes a gene which encodes a human xcex2 subunit, e.g., a xcex2-2 microglobulin gene. In other preferred embodiments the second transgene includes an HLA class I gene, e.g., an HLA A, B, C, or G gene. In preferred embodiments the first transgene includes an allele from a first reactivity group and the second transgene includes an allele from a second reactivity group. In preferred embodiments the first transgene includes an allele which is a member of a reactivity group, e.g., a Group 1 allele, e.g., any of an HLA C Cw2, Cw4, Cw5, or Cw6 allele, and the second transgene includes a Group 2 allele, e.g., any of an HLA C Cw1, Cw3, Cw7, or Cw8 allele. In other preferred embodiments the first transgene includes an allele which has an Asn at residue 77 and a Lys at residue 80 and the second transgene includes an allele which has a Ser at residue 77 and an Asn at residue 80.
In yet other preferred embodiments the organ or tissue includes one or more, or all, of a transgene which encodes an HLA A gene, a transgene which encodes an HLA B gene, a transgene which encodes an HLA C gene, a transgene which encodes an HLA G gene.
The swine organs and tissues of the invention can be used as a source for xe2x80x9chumanizedxe2x80x9d tissue for grafting into a human recipient, e.g., hematopoietic cells or other tissues or organs.
Graft tissue which expresses a recipient species-MHC class I gene can be used to improve methods of transplanting xenogeneic tissue into a recipient. For example, acceptance of porcine tissue by a human recipient can be prolonged if the porcine tissue expresses a human class I gene, preferably the HLA C gene. The use of graft tissue which expresses an HLA class I gene can be combined with methods of inducing tolerance described herein.
Accordingly, in another aspect, the invention features a method of inducing tolerance in a recipient mammal, e.g., a primate, e.g., a human, to a graft from a swine, e.g., a miniature swine. The method includes:
inserting DNA encoding a swine MHC antigen, preferably a class I antigen, a class II antigen, or both, into a hematopoietic stem cell, e.g., a bone marrow hematopoietic stem cell, of the recipient mammal;
allowing the MHC antigen encoding DNA to be expressed in the recipient; and
implanting the graft in the recipient, wherein some or substantially all of the cells of the graft express a recipient species class I gene which inhibits recipient NK cell mediated attack.
In preferred embodiments the graft tissue expresses an HLA C gene. The allele, by way of example, can be any Cw1, Cw2, Cw3, Cw4, Cw5, Cw6, Cw7, Cw8, Cw9, Cw7/8v, or Cw10 allele. In preferred embodiments the allele is a member of a reactivity group, e.g., a Group 1 allele, e.g., any of an HLA C Cw2, Cw4, Cw5, or Cw6 allele, or a Group 2 allele, e.g., any of an HLA C Cw1, Cw3, Cw7, or Cw8 allele. In other preferred embodiments the allele has an Asn at residue 77 and a Lys at residue 80 or a Ser at residue 77 and an Asn at residue 80.
In preferred embodiments the graft expresses an HLA A gene. In other preferred embodiments the graft expresses an HLA B gene. In other preferred embodiments the graft expresses an HLA G gene, e.g, any of alleles I-IV of HLA G. In yet other preferred embodiments the graft includes one or more, or all, of a transgene which encodes an HLA A gene, a transgene which encodes an HLA B gene, a transgene which encodes an HLA C gene, a transgene which encodes an HLA G gene.
In preferred embodiments: the graft includes a first transgene which includes an HLA class I allele, e.g., an HLA C allele, and a second transgene which includes a gene which encodes a class I MHC protein. In preferred embodiments the second transgene includes a human xcex2 subunit, e.g., a xcex2-2 microglobulin gene. In other preferred embodiments the first transgene includes an HLA class I allele from a first reactivity group and the second transgene includes an allele from the second reactivity group. For example, the first transgene includes a Group 1 allele, e.g., any of an HLA C Cw2, Cw4, Cw5, or Cw6 allele, and the second transgene includes a Group 2 allele, e.g., any of an HLA C Cw1, Cw3, Cw7, or Cw8 allele. In preferred embodiments the first transgene encodes an allele which has an Asn at residue 77 and a Lys at residue 80 and the second transgene encodes an allele which has a Ser at residue 77 and an Asn at residue 80. In other preferred embodiments the second transgene encodes a human xcex2 subunit, e.g., a xcex2-2 microglobulin gene.
In preferred embodiments the graft expresses a chimeric class I protein, e.g., chimeric HLA A, B, C, or G gene. For example, the chimeric gene includes a first portion derived from a first allele of the gene encoding the class I protein and a second portion derived from a second allele of the gene encoding the class I protein. In other embodiments, the class I gene is a synthetic sequence selected for the ability to produce a protein which protects a target cell from attack from more than one class of NK cells. In preferred embodiments the transgene includes a gene, e.g., a chimeric or mutated HLA C gene, which confers protection to more than one class of NK cells, e.g., an allele of HLA C having serine at position 77 and lysine at position 80.
In preferred embodiments the graft is from a transgenic swine, e.g., a transgenic swine which includes a transgenic human class I gene, e.g., an HLA A, B, C, or G gene.
In preferred embodiment, the method further includes: administering to the recipient a short course of help reducing treatment, e.g., a short course of high dose cyclosporine treatment. The short course of help reducing treatment is generally administered at about the time the graft is introduced into the recipient. The short course of help reducing treatment can induce tolerance to unmatched class I and/or minor antigens on a graft which is introduced into the recipient subsequent to expression of the MHC antigen. The duration of the short course of help reducing treatment should be approximately equal to or is less than the period required for mature T cells of the recipient species to initiate rejection of an antigen after first being stimulated by the antigen; in more preferred embodiments, the duration is approximately equal to or is less than two, three, four, five, or ten times the period required for a mature T cell of the recipient species to initiate rejection of an antigen after first being stimulated by the antigen. In other preferred embodiments, the short course of help reducing treatment is administered in the absence of a treatment which stimulates the release of a cytokine by mature T cells in the recipient, e.g., in the absence of a steroid drug in a sufficient concentration to counteract the desired effect of the help reducing treatment, e.g., in the absence of Prednisone (17, 21-dihydroxypregna-1, 4-diene-3, 11, 20-trione) at a concentration which stimulates the release of a cytokine by mature T cells in the recipient. In preferred embodiments, the short course of help reducing treatment is administered in the absence of a steroid drug, e.g., in the absence of Prednisone. In preferred embodiments: the help reducing treatment is begun before or at about the time the graft is introduced; the short course is perioperative; or the short course is postoperative.
Preferred embodiments include those in which: the recipient stem cell is removed from the recipient mammal prior to the DNA insertion and returned to the recipient mammal after the DNA insertion; the DNA is obtained from the individual mammal from which the graft is obtained; the DNA is obtained from an individual mammal which is syngeneic with the individual mammal from which the graft is obtained; the DNA is obtained from an individual mammal which is MHC matched, and preferably identical, with the individual mammal from which the graft is obtained; the DNA includes an MHC class I gene; the DNA includes an MHC class II gene; the DNA is inserted into the cell by transduction, e.g., by a retrovirus, e.g., by a Moloney-based retrovirus; and the DNA is expressed in bone marrow cells and/or peripheral blood cells of the recipient for at least 14, preferably 30, more preferably 60, and most preferably 120 days, after the DNA is introduced into the recipient.
Other preferred embodiments include: the step of, prior to hematopoietic stem cell transplantation, creating hematopoietic space, e.g., by irradiating the recipient mammal with low dose, e.g., between about 100 and 400 rads, whole body irradiation to deplete or partially deplete the bone marrow of the recipient; inactivating thymic T cells by one or more of: prior to hematopoietic stem cell transplantation, irradiating the recipient mammal with, e.g., about 700 rads of thymic irradiation, or administering to the recipient a short course of an immunosuppressant, as is described herein.
Other preferred embodiments include: the step of, prior to implantation of a graft, depleting natural antibodies from the blood of the recipient mammal, e.g., by hemoperfusing an organ, e.g., a liver or a kidney, obtained from a mammal of the second species. (In organ hemoperfusion antibodies in the blood bind to antigens on the cell surfaces of the organ and are thus removed from the blood.)
In other preferred embodiments: the method further includes, prior to hematopoietic stem cell transplantation, introducing into the recipient an antibody capable of binding to mature T cells of said recipient mammal.
Other preferred embodiments further include the step of introducing into the recipient a graft obtained from the donor, e.g., a liver or a kidney.
In preferred embodiments: the donor graft cells are other than a hematopoietic stem cells, or other blood cells; the donor graft cells are swine thymic cells, e.g., swine thymic stromal cells; the donor graft cells are bone marrow stromal cells; the donor graft cells are swine liver cells; the donor graft cells are swine kidney cells; the donor graft cells are swine epithelial cells; the donor graft cells are swine muscle cells, e.g., heart cells; the donor graft cells are swine neuronal cells; the graft cells include an organ, e.g., a kidney, a liver, or a heart; the donor graft cells include dendritic cells or their precursors.
Other preferred embodiments include: the step of introducing into the recipient, donor species-specific stromal tissue, preferably hematopoietic stromal tissue, e.g., fetal liver or thymus. In preferred embodiments: the stromal tissue is introduced simultaneously with, or prior to, the hematopoietic stem cells.
In another aspect, the invention features a method of inducing tolerance in a recipient mammal, e.g., a primate, e.g., a human, to a graft obtained from a donor swine, e.g., a miniature swine. The method includes:
preferably prior to or simultaneous with transplantation of the graft, introducing, e.g., by intravenous injection, into the recipient mammal, swine hematopoietic stem cells, e.g., bone marrow cells or fetal liver or spleen cells (preferably the hematopoietic stem cells home to a site in the recipient mammal);
(optionally) inactivating the natural killer cells of the recipient mammal, e.g., by prior to introducing the hematopoietic stem cells into the recipient mammal, introducing into the recipient mammal an antibody capable of binding to natural killer cells of said recipient mammal; and
implanting the graft in the recipient, provided that one or both of: the stem cells, or some or substantially all of the cells of the graft, express a recipient species class I gene which inhibits recipient NK cell mediated attack.
In preferred embodiments either or both, a stem cell or the graft tissue, expresses an HLA C allele. The allele, by way of example, can be any Cw1, Cw2, Cw3, Cw4, Cw5, Cw6, Cw7, Cw8, Cw9, Cw7/8v, or Cw10 allele. In preferred embodiments the allele is a member of a reactivity group, e.g., a Group 1 allele, e.g., any of an HLA C Cw2, Cw4, Cw5, or Cw6 allele, or a Group 2 allele, e.g., any of an HLA C Cw1, Cw3, Cw7, or Cw8 allele. In other preferred embodiments the allele has an Asn at residue 77 and a Lys at residue 80 or a Ser at residue 77 and an Asn at residue 80.
In preferred embodiments either or both, a stem cell or the graft tissue, expresses an HLA A gene. In other preferred embodiments either or both, a stem cell or the graft tissue, graft expresses an HLA B gene. In other preferred embodiments either or both, a stem cell or the graft tissue, expresses an HLA G gene, e.g, any of alleles I-IV of HLA G. In preferred embodiments either or both, a stem cell or the graft tissue, includes one or more, or all, of a transgene which encodes an HLA A gene, a transgene which encodes an HLA B gene, a transgene which encodes an HLA C gene, a transgene which encodes an HLA G gene.
In preferred embodiments: either or both, a stem cell or the graft tissue, includes a first transgene which includes an HLA class I allele, e.g., an HLA C allele, and a second transgene which includes a gene which encodes a class I MHC protein. In preferred embodiments the second transgene includes a human xcex2 subunit, e.g., a xcex2-2 microglobulin gene. In other preferred embodiments the first transgene includes an HLA class I allele from a first reactivity group and the second transgene includes an allele from a second reactivity group. For example, the first transgene includes a Group 1 allele, e.g., any of an HLA C Cw2, Cw4, Cw5, or Cw6 allele, and the second transgene includes a Group 2 allele, e.g., any of an HLA C Cw1, Cw3, Cw7, or Cw8 allele. In other preferred embodiments the first transgene includes an allele which has an Asn at residue 77 and a Lys at residue 80 and the second transgene includes an allele which has a Ser at residue 77 and an Asn at residue 80.
In preferred embodiments either or both, a stem cell or the graft tissue, expresses a chimeric class I protein, e.g., chimeric HLA A, B, C, or G gene. For example, the chimeric gene includes a first portion derived from a first allele of the gene encoding the class I protein and a second portion derived from a second allele of the gene encoding the class I protein. In other embodiments, the class I gene is a synthetic sequence selected for the ability to produce a protein which protects a target cell from attack from more than one class of NK cells. In preferred embodiments the transgene includes a gene, e.g., a chimeric or mutated HLA C gene, which confers protection to more than one class of NK cells, e.g., an allele of HLA C having serine at position 77 and lysine at position 80.
In preferred embodiments either or both, a stem cell or the graft tissue, is from a transgenic swine, e.g., a transgenic swine which includes a transgenic human class I gene, e.g., an HLA A, B,C, or G gene.
In preferred embodiment, the method further includes: administering to the recipient a short course of help reducing treatment, e.g., a short course of high dose cyclosporine treatment. The short course of help reducing treatment is generally administered at about the time the graft is introduced into the recipient. The short course of help reducing treatment can induce tolerance to unmatched class I and/or minor antigens on a graft which is introduced into the recipient subsequent to expression of the MHC antigen. The duration of the short course of help reducing treatment should be approximately equal to or is less than the period required for mature T cells of the recipient species to initiate rejection of an antigen after first being stimulated by the antigen; in more preferred embodiments, the duration is approximately equal to or is less than two, three, four, five, or ten times the period required for a mature T cell of the recipient species to initiate rejection of an antigen after first being stimulated by the antigen. In other preferred embodiments, the short course of help reducing treatment is administered in the absence of a treatment which stimulates the release of a cytokine by mature T cells in the recipient, e.g., in the absence of a steroid drug in a sufficient concentration to counteract the desired effect of the help reducing treatment, e.g., in the absence of Prednisone (17, 21-dihydroxypregna-1,4-diene-3, 11, 20-trione) at a concentration which stimulates the release of a cytokine by mature T cells in the recipient. In preferred embodiments, the short course of help reducing treatment is administered in the absence of a steroid drug, e.g., in the absence of Prednisone. In preferred embodiments: the help reducing treatment is begun before or at about the time the graft is introduced; the short course is perioperative; or the short course is postoperative.
The hematopoietic cells prepare the recipient for the graft that follows, by inducing tolerance at both the B-cell and T-cell levels. Preferably, hematopoietic cells are fetal liver or spleen, or bone marrow cells, including immature cells (i.e., undifferentiated hematopoietic stem cells; these desired cells can be separated out of the bone marrow prior to administration), or a complex bone marrow sample including such cells can be used.
One source of anti-NK antibody is anti-human thymocyte polyclonal anti-serum. As is discussed below, preferably, a second anti-mature T cell antibody can be administered as well, which lyses T cells as well as NK cells. Lysing T cells is advantageous for both bone marrow and xenograft survival. Anti-T cell antibodies are present, along with anti-NK antibodies, in anti-thymocyte anti-serum. Repeated doses of anti-NK or anti-T cell antibody may be preferable. Monoclonal preparations can be used in the methods of the invention.
Other preferred embodiments include: the step of introducing into the recipient mammal, donor species-specific stromal tissue, preferably hematopoietic stromal tissue, e.g., fetal liver or thymus. In preferred embodiments: the stromal tissue is introduced simultaneously with, or prior to, the hematopoietic stem cells; the hematopoietic stem cells are introduced simultaneously with, or prior to, the antibody.
Other preferred embodiments include those in which: the same mammal of the second species is the donor of one or both the graft and the hematopoietic cells; and the antibody is an anti-human thymocyte polyclonal anti-serum, obtained, e.g., from a horse or pig.
Other preferred embodiments include: the step of, prior to hematopoietic stem cell transplantation, creating hematopoietic space, e.g., by irradiating the recipient mammal with low dose, e.g., between about 100 and 400 rads, whole body irradiation to deplete or partially deplete the bone marrow of the recipient; inactivating thymic T cells by one or more of: prior to hematopoietic stem cell transplantation, irradiating the recipient mammal with, e.g., about 700 rads of thymic irradiation, or administering to the recipient a short course of an immunosuppressant, as is described herein.
Other preferred embodiments include: the step of, prior to hematopoietic stem cell transplantation, depleting natural antibodies from the blood of the recipient mammal, e.g., by hemoperfusing an organ, e.g., a liver or a kidney, obtained from a mammal of the second species. (In organ hemoperfusion antibodies in the blood bind to antigens on the cell surfaces of the organ and are thus removed from the blood.)
In other preferred embodiments: the method further includes, prior to hematopoietic stem cell transplantation, introducing into the recipient an antibody capable of binding to mature T cells of said recipient mammal.
In other preferred embodiments: the method further includes inactivating T cells of the recipient, e.g., by, prior to introducing the hematopoietic stem cells into the recipient, introducing into the recipient an antibody capable of binding to T cells of the recipient.
In preferred embodiments, the method includes the step of introducing into the recipient a graft obtained from the donor which is obtained from a different organ than the hematopoietic stem cells, e.g., a liver or a kidney.
In preferred embodiments: the donor graft cells are other than a hematopoietic stem cells, or other blood cells; the donor graft cells are swine thymic cells, e.g., swine thymic stromal cells; the donor graft cells are bone marrow stromal cells; the donor graft cells are swine liver cells; the donor graft cells are swine kidney cells; the donor graft cells are swine endothelial cells; the donor graft cells are swine epithelial cells; the donor graft cells are swine muscle cells, e.g., heart cells; the donor graft cells are swine neuronal cells; the graft cells include an organ, e.g., a kidney, a liver, or a heart; the donor graft cells include dendritic cells or their precursors.
Other preferred embodiments include: the step of introducing into the recipient, donor species-specific stromal tissue, preferably hematopoietic stromal tissue, e.g., fetal liver or thymus. In preferred embodiments: the stromal tissue is introduced simultaneously with, or prior to, the hematopoietic stem cells.
Genetically engineered swine cells of the invention can be made by methods known to those skilled in the art, e.g., by retroviral transduction of swine cells. Methods for producing transgenic swine of the invention use standard transgenic technology. These methods include, e.g., the infection of the zygote or organism by viruses including retroviruses; the infection of a tissue with viruses and then reintroducing the tissue into an animal; and the introduction of a recombinant nucleic acid molecule into an embryonic stem cell of a mammal followed by appropriate manipulation of the embryonic stem cell to produce a transgenic animal. In particular, the invention features a transgenic swine, whose germ cells and somatic cells contain a transgene including a DNA sequence encoding a polypeptide and a tissue-specific promoter operably linked to the DNA sequence, wherein the tissue-specific promoter effects expression of the hematopoietic peptide in bone marrow cells of the swine, the transgene being introduced into embryonal cells of the animal, or an ancestor of the animal.
In another aspect, the invention features, a method of inducing tolerance in a recipient mammal, e.g., a primate, e.g., a human, to a graft obtained from a swine, e.g., a miniature swine. The method includes:
prior to or simultaneous with transplantation of the graft, introducing into the recipient mammal, swine thymic tissue, e.g., thymic epithelium, preferably fetal or neonatal thymic tissue; and
implanting the graft in the recipient. The thymic tissue prepares the recipient for the graft that follows, by inducing immunological tolerance at the T-cell level. Either or both of, the thymic tissue, or some or all of the cells of the graft, express a recipient species class I gene which inhibits recipient NK cell mediated attack.
In preferred embodiments either or both of, the thymic tissue, or some or all of the cells of the graft, expresses an HLA C allele. The allele, by way of example, can be any Cw1, Cw2, Cw3, Cw4, Cw5, Cw6, Cw7, Cw8, Cw9, Cw7/8v, or Cw10 allele. In preferred embodiments the allele is a member of a reactivity group, e.g., a Group 1 allele, e.g., any of an HLA C Cw2, Cw4, Cw5, or Cw6 allele, or a Group 2 allele, e.g., any of an HLA C Cw1, Cw3, Cw7, or Cw8 allele. In other preferred embodiments the allele has an Asn at residue 77 and a Lys at residue 80 or a Ser at residue 77 and an Asn at residue 80.
In preferred embodiments either or both of, the thymic tissue, or some or all of the cells of the graft, expresses an HLA A gene. In other preferred embodiments either or both of, the thymic tissue, or some or all of the cells of the graft, expresses an HLA B gene. In other preferred embodiments either or both of, the thymic tissue, or some or all of the cells of the graft, expresses an HLA G gene, e.g, any of alleles 14V of HLA G. In preferred embodiments either or both of, the thymic tissue, or some or all of the cells of the graft, includes one or more, or all, of a transgene which encodes an HLA A gene, a transgene which encodes an HLA B gene, a transgene which encodes an HLA C gene, a transgene which encodes an HLA G gene
In preferred embodiments: either or both of, the thymic tissue, or some or all of the cells of the graft, includes a first transgene which includes an HLA class I allele, e.g., an HLA C allele, and a second transgene which includes a gene which encodes a class I MHC protein. In preferred embodiments the second transgene includes a human xcex2 subunit, e.g., a xcex2-2 microglobulin gene. In other preferred embodiments the first transgene includes an HLA class I allele from a first reactivity group and the second transgene includes an allele from a second reactivity group. For example, the first transgene includes a Group 1 allele, e.g., any of an HLA C Cw2, Cw4, Cw5, or Cw6 allele, and the second transgene includes a Group 2 allele, e.g., any of an HLA C Cw1, Cw3, Cw7, or Cw8 allele. In other preferred embodiments the first transgene includes an allele which has an Asn at residue 77 and a Lys at residue 80 and the second transgene includes an allele which has an a Ser at residue 77 and an Asn at residue 80.
In preferred embodiments either or both of, the thymic tissue, or some or all of the cells of the graft, expresses a chimeric class I protein, e.g., chimeric HLA A, B, C, or G gene. For example, the chimeric gene includes a first portion derived from a first allele of the gene encoding the class I protein and a second portion derived from a second allele of the gene encoding the class I protein. In other embodiments, the class I gene is a synthetic sequence selected for the ability to produce a protein which protects a target cell from attack from more than one class of NK cells. In preferred embodiments the transgene includes a gene, e.g., a chimeric or mutated HLA C gene, which confers protection to more than one class of NK cells, e.g., an allele of HLA C having serine at position 77 and lysine at position 80.
In preferred embodiments either or both of, the thymic tissue, or some or all of the cells of the graft, is from a transgenic swine, e.g., a transgenic swine which includes a transgenic human class I gene, e.g., an HLA A, B, C, or G gene.
Preferred embodiments include other steps to promote acceptance of the graft thymus and the induction of immunological tolerance or to otherwise optimize the procedure. In preferred embodiments: liver or spleen tissue, preferably fetal or neonatal liver or spleen tissue, is implanted with the thymic tissue; donor hemopoietic cells, e.g., cord blood stem cells or fetal or neonatal liver or spleen cells, are administered to the recipient, e.g., a suspension of fetal liver cells administered intraperitoneally or intravenously; the recipient is thymectomized, preferably before or at the time the xenograft thymic tissue is introduced.
In other preferred embodiments the method includes (preferably prior to or at the time of introducing the thymic tissue or stem cells into the recipient) depleting, inactivating or inhibiting recipient NK cells, e.g., by introducing into the recipient an antibody capable of binding to natural killer (NK) cells of the recipient, to prevent NK mediated rejection of the thymic tissue; (preferably prior to or at the time of introducing the thymic tissue into the recipient) depleting, inactivating or inhibiting recipient T cells, e.g., by introducing into the recipient an antibody capable of binding to T cells of the recipient; (preferably prior to or at the time of introducing the thymic tissue or stem cells into the recipient) depleting, inactivating or inhibiting host CD4+ cell function, e.g., by introducing into the recipient an antibody capable of binding to CD4, or CD4+ cells of the recipient. An anti-mature T cell antibody which lyses T cells as well as NK cells can be administered. Lysing T cells is advantageous for both thymic tissue and xenograft survival. Anti-T cell antibodies are present, along with anti-NK antibodies, in anti-thymocyte anti-serum. Repeated doses of anti-NK or anti-T cell antibody may be preferable. Monoclonal preparations can be used in the methods of the invention.
Other preferred embodiments include those in which: the recipient does not receive hemopoietic cells from the donor or the donor species: the same mammal of the second species is the donor of both the graft and the thymic tissue; the donor mammal is a swine, e.g., a miniature swine; an anti-human thymocyte polyclonal anti-serum, obtained, e.g., from a horse or pig is administered to the recipient.
Other preferred embodiments include the step of (preferably prior to thymic tissue or hematopoietic stem cell transplantation) creating hematopoietic space, e.g., by one or more of: irradiating the recipient mammal with low dose, e.g., between about 100 and 400 rads, whole body irradiation, the administration of a myelosuppressive drug, the administration of a hematopoietic stem cell inactivating or depleting antibody, to deplete or partially deplete the bone marrow of the recipient.
Other preferred embodiments include (preferably prior to thymic tissue or hematopoietic stem cell transplantation) inactivating thymic T cells by one or more of: irradiating the recipient with, e.g., about 700 rads of thymic irradiation, administering to the recipient one or more doses of an anti T cell antibody, e.g., an anti-CD4 and/or an anti-CD8 monoclonal antibody, or administering to the recipient a short course of an immunosuppressant.
In preferred embodiments the host or recipient is a post-natal individual, e.g., an adult, or a child.
In preferred embodiments the method further includes the step of identifying a host or recipient which is in need of a graft.
Other preferred embodiments include depleting or otherwise inactivating natural antibodies, e.g., by one or more of: the administration of a drug which depletes or inactivates natural antibodies, e.g., deoxyspergualin; the administration of an anti-IgM antibodies; or the absorption of natural antibodies from the recipient""s blood, e.g., by contacting the hosts blood with donor antigen, e.g., by hemoperfusion of a donor organ, e.g., a kidney or a liver, from the donor species.
As is discussed herein, killer inhibitory receptors (KIR""s) found on NK cells are specific for polymorphic MHC class I molecules. Swine tissue used for grafts should express an HLA class I allele (or alleles) which will maximize protection from the NK cells of the recipient. Thus, in another aspect, the invention includes a method of prolonging acceptance of a swine xenograft tissue by a human which includes:
determining the HLA A, HLA B, HLA C, or HLA G phenotype or genotype of the recipient;
choosing donor tissue, e.g., choosing a donor transgenic animal, which expresses a recipient HLA gene which will confer protection against recipient NK cells and implanting the tissue in the recipient. For example, the donor tissue or animal can express a transgenic form of an allele expressed by the recipient. Alternatively, the donor tissue or animal can express an allele from the same reactivity group as one or more of the alleles expressed in the recipient.
The recipient""s HLA A, B, C, or G phenotype or genotype can be determined by standard methods, e.g., by PCR or lymphocyte toxicity.
In another aspect, the invention includes, a panel of transgenic swine including a first transgenic swine and a second transgenic swine. The first transgenic swine has a transgene which includes a first allele of a human HLA A, B, C, or G gene, and the second transgenic swine has a transgene which includes a second allele of the human HLA A, B, C, or G gene. In preferred embodiments the first allele is from a first reactivity group and the second allele is from a second reactivity group. For example, the transgene of the first swine includes a Group 1 allele, e.g., any of an HLA C Cw2, Cw4, Cw5, or Cw6 allele, and the transgene of the second swine includes a Group 2 allele, e.g., any of an HLA C Cw1, Cw3, Cw7, or Cw8 allele. In other preferred embodiments transgene of the first swine includes an allele which has an Asn at residue 77 and a Lys at residue 80 and the transgene of the second swine includes an allele which has an a Ser at residue 77 and an Asn at residue 80. The panel of transgenic swine can be used to supply a donor having an HLA class I allele which will protect a graft from a recipient""s NK cells.
NK cells play an important role in the rejection of xenogeneic tissues. Because NK cell killing is inhibited by the presence of class I antigens of the NK cell type on the target cells, NK-mediated attack of porcine tissues by human NK cells is minimized by the invention. This is achieved by introducing a human class I gene into the porcine target.
In contrast to allogeneic cell-mediated killing, xenogeneic human anti-porcine cytotoxicity includes an important contribution from NK cells. Normal autologous and most allogeneic cells are not susceptible to natural killer (NK) cell mediated cytotoxicity due to the expression of major histocompatibility complex (MHC) class I molecules. The preventive signal is delivered to the NK cells through KIR""s with different MHC class I specificities. Xenogeneic porcine MHC class I molecules appear not to be recognized by human KIR""s and thus render porcine cells susceptible to NK cell-mediated lysis.
Other features and advantages of the invention will be apparent from the following detailed description, and from the claims.

Transgenic swine and swine cells having human HLA genes


A device for measuring dynamic balance of a rotor including a shaft to which an impeller is secured at its one end and which has a neck portion adjacent to the impeller so that the shaft may be rotatably supported by a bearing member at the neck portion. The device comprises: a housing member, a thrust bearing secured to the housing member and engageable with the neck portion of the shaft, a support member provided in the housing member beneath the thrust bearing and engageable with the shaft so that the shaft may be rotatably supported in a slanted or a vertical position by the support member and the thrust bearing with the impeller being positioned upward, and a sensor connected to the housing member for detecting the vibration of the housing member caused when the rotor supported by the thrust bearing and the support member is rotated. The dynamic balance of the rotor can be measured by the sensor in terms of the vibration of the housing.

This invention relates to a device for measuring dynamic balance of a rotor for turbochargers, gas turbines, etc.
FIG. 5 depicts an example of a turbocharger, in which the reference numeral 1 denotes a cantilever rotor composed of a shaft 2 and impellers 3 and 4 fixedly secured to opposite ends of the shaft 2. The rotor 1 is rotatably received by a pair of ball bearings 6a and 6b supported by a housing 7. The ball bearing 6a is engaged with a neck portion 5 of the shaft 2 which is formed adjacent to the impeller 3. The impeller 3 is disposed within a gas feed passage 8 while the impeller 4 is disposed within a gas exhaust passage 9.
In such a turbocharger or the like gas turbine, it is important that the rotor 2 should exhibit good dynamic balance during its rotation, since otherwise the rotation causes vibration of bearings 6a and 6b and other associated parts. Machining errors during manufacture of the impellers, shaft and other components of the rotor generally cause dynamic unbalance of the rotor.
There is known a device which can detect and evaluate the dynamic balance of such rotors. The conventional device includes a housing, two or more ball bearings secured to the housing for rotatably supporting the rotor in a substantially horizontal position, and a sensor for detecting vibration of the housing caused as a result of the rotation of the rotor supported by the bearings.
In the conventional dynamic balance measuring device, the weight of the rotor is supported in the radial direction (in the direction perpendicular to the axis of the rotor shaft) only, because the rotor shaft is maintained in a horizontal position. It has been found, however, that vibration in the thrust direction (in the direction parallel to the axis of the rotor shaft) should not be ignored in order to precisely evaluate the dynamic balance of the rotor. That is, with the conventional device, a portion of the vibration in the radial direction is relaxed as a result of the sliding of the shaft in the axial direction so that the measured value involves a measuring error which cannot be disregarded.

Device for measuring dynamic balance of a rotor


Multiple relays are different distances from their respective donor access nodes. The donor and relay path selected for a user's traffic is selected based on the priority associated with that user and a ratio of a channel quality indicator and the distance of the donor-relay link. Traffic associated with a higher priority user is routed via a path with a good channel quality indicator to distance ratio whereas traffic for other, lower QoS profile, users does not take channel quality or relay-to-donor distance into account.

Wireless communication may be used as a means of accessing a network. Wireless communication has certain advantages over wired communications for accessing a network. One of those advantages is a lower cost of infrastructure to provide access to many separate locations or addresses compared to wired communications. This is the so-called "last mile" problem. Another advantage is mobility. Wireless communication devices, such as cell phones, are not tied by wires to a fixed location. To use wireless communication to access a network, a customer needs to have at least one transceiver in active communication with another transceiver that is connected to the network.
To facilitate wireless communications, the Institute of Electrical and Electronics Engineers (IEEE) has promulgated a number of wireless standards. These include the 802.11 (WiFi) standards and the 802.16 (WiMAX) standards. Likewise, the International Telecommunication Union (ITU) has promulgated standards to facilitate wireless communications. This includes TIA-856, which is also known as Evolution-Data Optimized (EV-DO). The European Telecommunications Standards Institute (ETSI) has also promulgated a standard known as long term evolution (LTE). Additional standards such as the fourth generation communication system (4G) are also being pursued. These standards pursue the aim of providing a comprehensive IP solution where voice, data, and streamed multimedia can be given to users on an "anytime, anywhere" basis. These standards also aim to provide higher data rates than previous generations. All of these standards may include specifications for various aspects of wireless communication with a network. These aspects include processes for registering on the network, carrier modulation, frequency bands of operation, and message formats.
Relay nodes can be provided in 4G networks to increase capacity and expand coverage area by facilitating communication between wireless devices and access nodes. For example, a relay access node can establish a backhaul link with a donor access node. The relay access node can establish access links with one or more wireless devices. This can improve the capacity and coverage in areas near to the relay access node—particularly when the relay access node is near the edge of the donor access node's coverage area.

Quality of service enhancement for wireless relay networks


[Object] To provide an information processing apparatus by which sound can be smoothly re-listened to.

A function of re-listening of missing sound when a user misses some sound in a hearing-aid apparatus is provided. According to Patent Literature 1, for example, a past sound signal to be listened to again and current input sound are provided at the same time after processing is performed thereon such that the past sound signal and the current input sound can be easily distinguished.

Information processing apparatus, information processing system, and program

Abstract: [Solution] There is provided an information processing apparatus including: a reproduction processing unit that performs reproduction of a recorded sound on a basis of a reproduction start instruction for starting re-listening of the recorded sound from a position tracking back a predetermined time from a reproduction start time, at which the reproduction start instruction is input, to a position of a present time.


An end cutter includes a pair of rollers (64,73) operatively arranged to frictionally engage cloth passing through the nip thereof. One of the rollers is mounted for unidirectional rotation such that the cloth may be pulled forwardly from a roll, but cannot retract when such pulling force is released. The logic includes a pressure comparator and pneumatically-operated safety dump valve (92,94) for sensing whether the cutter (31) has encountered a motion-impeding obstruction on its forward cutting stroke, and automatically releases the force urging the cutter to move forwardly in such event. The cutter is mounted on a rodless cylinder (48).

In the preparation of finished fabric goods, such as clothing and the like, it is first necessary to unwind cloth from a roll. The unwound cloth is cut into sheets of desired lengths, and such sheets are then superimposed on top of one another to form a stack of cut plies of such material. Thereafter, a suitable pattern may be placed on top of the stack, and the entire stack may be cut en banc according to the pattern to form various individual pieces, which are then sent to subsequent sewing and finishing stations.
The present invention provides an automatic end cutter for use in such cloth spreading and cutting apparatus. One example of a prior art automatic end cutter is shown and described in U.S. Pat. No. 4,779,500, the aggregate disclosure of which is hereby incorporated by reference, and which is assigned to the assignee of the present application. That patent discloses an end cutter in which cloth is unwound from a roll, and is pulled along a cloth spreading table. The patent also shows and describes an automated means for cutting an end length from the unwound cloth. Basically, cloth is first pulled from the roll and is spread upon the table. A cutter is then energized and moved forwardly across the table to sever an end length from the roll. After this length has been cut, the cutter is returned to its initial position. At this point, the cutter and carriage are automatically lifted and lowered to clamp the trailing end of the just-cut length of cloth, and any plies therebeneath. Operators on either side of the table then grasp the free or cut end of the cloth, and pull another length from the roll so as to overlie the previously cut length, and the cutting operation is repeated.
While the device disclosed in the '500 patent does provide a type of automated end cutter, a number of problems have persisted. First, when cloth is pulled from a roll, the unwound length of cloth is put in tension. When released, the advanced length has a tendency to retract or move back toward the roll. Thus, as a practical matter, it is somewhat difficult to accurately position the unwound length at the desired location of the intended cut.
Secondly, the '500 patent discloses a belt-type arrangement for selectively raising the cutter and carriage relative to the table. The carriage and cutter were returned to their lowered position by the force of gravity, amplified by a weight mounted on the distal end of the belt. Thus, the downward clamping force was substantially constant. Upon further reflection and experience, it is felt that it would be desirable to exert a variable downward force on the stack of cut sheets or plies at a controllable down-pressure, in order to more easily accommodate different types of cloth.
Thirdly, the '500 patent did not have a mechanism for stopping the advance of the cutter in the event that cloth "bunched" ahead of the cutter to provide an impediment to the forward motion of the cutter.
Accordingly, it would be generally desirable to provide an improved automatic end cutter incorporating features to solve these problems.

Unidirectional pinch rollers for a cloth spreading machine


A method and apparatus for supplying gypsum slurry of predetermined concentration to a follow-on utilization device, such as an irrigation network. Slurry of a first higher concentration is prepared in a vessel using a vertically arranged mixer with power and drive components mounted outside the tank and a mixer shaft bearing an impeller and a propeller positioned inside the tank for immersion in the slurry ingredients. Rotation of the impeller and propeller causes the slurry ingredients to flow downwardly in the central region of the vessel, outwardly near the bottom towards the inner wall surfaces, upwardly of the inner wall surfaces towards the top and inwardly to the central region in a cyclic fashion to produce a uniform slurry. The slurry is withdrawn through an outlet in one of the tank walls and mixed with externally supplied water in a mixing chamber to dilute the slurry to a desired useable concentration. The added water is supplied via an adjustable flow meter to obtain the desired diluted concentration. Once the diluted concentration has been selected, a uniform concentration is maintained throughout the delivery cycle, regardless of the level of the slurry in the vessel.

This invention relates to water amendment technology in general. More particularly, this invention relates to methods and systems for combining a mixed component in the form of a slurry with water so as to effect remediation of the water for some utilization purpose, such as to affect soil conditions using an irrigation network.
Methods and systems are known for combining make-up water with gypsum in order to provide a slurry of predetermined initial starting concentration for the purpose of affecting soil conditions. In a typical application, a measured amount of powdered gypsum is mixed with a known volume of make-up water in order to provide a slurry of preselected initial density, depending upon the calculated soil remediation requirements, the mixture being prepared in a holding tank of special design located adjacent the inlet to an irrigation facility. The slurry mixture is then pumped from the tank to the inlet of the irrigation system, adding fresh make-up water to the tank as the slurry level in the tank drops below a predetermined minimum level. The slurry mixture in the tank is agitated continuously during the withdrawal process in order to maintain a uniform suspension of gypsum particles in water.
Known slurry make-up and distribution systems suffer from a number of disadvantages. Firstly, the agitation mechanisms used in most tanks are disposed within the tank itself, typically in a horizontal attitude. With slurry in the tank above the level of the agitator, the bearings used to mount the agitator shaft for rotation are physically contacted by the slurry mixture, which is highly abrasive to most bearing materials. As a consequence, the agitator bearings are prone to premature failure and require costly replacement. In addition, the mounting of the agitator is typically done through the end or side walls of the tank, which places large mechanical loads on these walls. The walls must thus either be reinforced at additional cost to resist these forces, or will be subject to premature failure in a form of cracking or bending.
Another disadvantage with known slurry tank configurations lies in the use of additional make-up water when the slurry level drops below a predetermined lower threshold. When additional make-up water is added to the existing slurry mixture in the tank, the density of the slurry changes. Unless this change can somehow be compensated for, the efficacy of the soil treatment is impaired and the optimum desired soil effect will never be attained. In some cases, it is possible to partially counter the effective slurry dilution by simply carrying on the slurry treatment for a longer period of time: however, at best, this adds additional water cost to the soil treatment process and, at worst, does not result in the proper amount of calcium irrigated into the soil.
Efforts to date to provide a slurry tank based soil conditioning system devoid of the above disadvantages have not met with success.

Method and system for slurry preparation and distribution


A system for entering data in a format that is easy to use, enabling selection of encoding format and displaying the resulting search data string in format to enable generation of byte sets for supplying to free string match algorithm for application to network data.

This invention relates to encoding and previewing of search string data.
In network test environments, for example, a technician is often looking for particular data strings, for the purpose of debugging or testing the network, or searching for networking problems or event occurrences.
Communications protocols have generally well defined structures consisting of specifications for the order and contents of fields within a message. Fields within a data stream in a given protocol may be sent in packets, a combination of values that control the flow of data, sometimes referred to as protocol header fields, or payload fields that contain information that is exchanged between devices on a network.
Information contained in a packet is often "encoded" to facilitate efficient processing by the computer applications that generate or consume the packet.
Since a network may be employing a variety of communication protocols and data encoding types, it can be cumbersome or impossible to find a particular data set or string in raw data received by a network test instrument.
The strings may be plain text, e.g. "uspto", but are more likely specific values described by the protocol a user is attempting to troubleshoot. Even plain text maybe encoded within a data packet using several different schemes, such as ASCII or Unicode. The protocol, the network or the operating systems of the devices being monitored may also affect the "byte order" of the data.
In a network test and measurement situation, for a user of packet capture applications for network testing, creating an encoded packet filter or trigger specification, to look for data or activity on the network as a part of the testing/measuring, can be difficult and error-prone, as the different protocols and encodings that may be in use result in data on the network that is complex to decode manually. Translating values that a user is interested in to the specifications required by the string match algorithm can be difficult, because a given encoding may involve complex rules. But such translation is heretofore been required, so that the user can specify to the string match algorithm what it is that is to be matched.
Without the ability to filter data packets, high speed, high utilization interfaces common in computer networks can quickly fill the packet capture capability of software and hardware-based packet analysis applications and devices.
Accordingly, some manner of filtering and easily specifying the filter values becomes desirable.


When a first floor (11) which is formed of a punching plate or the like and through which air passes is provided immediately below an arm (17) at a middle height part of a conveying robot (10) in a casing (2a) of a clean transfer device (2) and a degree of opening of a casing bottom part frame (2b), which supports a base part of the conveying robot (10), with respect to the outside is restricted, a class 1 can be maintained. Here, when a second floor (13) formed of a punching plate or the like is used on the casing bottom part frame (2b), a class 0 state can be realized under specific conditions, thereby enabling production of a semiconductor having a wire width of 0.1 μm. As a result, the device can cope with the unexpectedly high degree of cleanliness of 0.1 μm particle class 1, which cannot be realized in the prior art, requested also for the transfer device according to a reduction in wire width on a highly integrated semiconductor wafer.

In a conventional clean booth as a cleaning space, as disclosed in, e.g., Japanese Patent Application Laid-open No. 1990-4145, there has been adopted a method by which clean air supplied from an HEPA (High Efficiency Particulate Air) filter or a ULPA (Ultra Low Penetration Air) filter set on a ceiling of a box-like body blows down foreign particles and these foreign particles are discharged to the outside from a grating floor formed of a perforated plate. In recent years, however, in a manufacturing process for a sheet-like electronic component as typified by a semiconductor wafer with a wire width of 1 μm or below from which contamination due to grained foreign particles or organic matters must be completely eliminated, a highly cleansed clean booth called a mini-environment has been used. As an example of this type of booth, in Japanese Patent Application Laid-open No. 2001-244315, although an apparatus which computer-controls a displacement volume by providing an exhaust system to a body of a conveying robot as a foreign particle generation source is proposed, but its quantitative effect is not described.
When a robot which may possibly generate dust is not used, although a class 10 or a lower class is achieved with respect to dust of 0.3 μm in an apparatus disclosed in, e.g., Japanese Patent Application Laid-open No. 2000-161735, this value is not sufficient when processing a semiconductor wafer whose wire width is not more than 0.5 μm. Further, in the apparatus disclosed in Japanese Patent Application Laid-open No. 2001-244315, there is a case in which a robot or an opening/closing door as a foreign particle generation source moves in a clean booth or a case in which foreign particles soar above with eddy currents generated on the rear side of a sheet-like matter, a cleanness is insufficient, and installation of an expensive computer-controlled system increases a facility cost, which is not desirable.

Sheet-like electronic component clean transfer device and sheet-like electronic component manufacturing system


Apparatus and methods provide for a structural joint utilizing overlapping blade stringers coupled to opposing sides of a continuous skin. According to embodiments described herein, a structural joint includes a number of inside blade stringers associated with a first component are coupled to an inside surface of a continuous skin. A number of outside blade stringers associated with a second component may be coupled to an outside surface of the continuous skin. The inside blade stringers and outside blade stringers may overlap on opposing surfaces of the continuous skin.

Aircraft, as well as other types vehicles and structures, utilize stringers to provide strength and stiffening characteristics to skin that covers various surfaces of the aircraft or structure. As two components converge at a joint, conventional techniques include terminating the stringers from each component and skin at one or more metallic splice plates that provide the desired reinforcement to the joint. When utilizing composite materials for the stringers and skin, the potential for delamination exists at these joints where increased loads and corresponding moments are common. To accommodate excessive forces at these joints and prevent delamination and composite failure, these conventional joints and associated splice plates are commonly complex and undesirably heavy.
It is with respect to these considerations and others that the disclosure made herein is presented.

Structural joint having continuous skin with inside and outside stringers


A pressure-sensed ink-filled pen comprises at least a pen tube, a valve, a filler seat and a filler. An ink outlet is formed within the front portion of the pen tube. An U-shape valve made of a relatively soft material is mounted in front of the ink outlet. A filler seat embedding a filler at the front end thereof is received in a flexible relation within the front portion of the pen tube, allowing a longitudinal movement. By pressing the filler and the filler seat at one end to cause another end to open the valve, a pressure-sensed ink-filled pen with proper ink supply is formed.

(a) Field of the Invention
The invention relates to pressure sensed ink-filled pen and more particularly to a structural improved pen with pen tube filled with ink for the filler to absorb, by which proper measure of ink is supplied to avoid waste of ink and leads to structural simplification and reduction of cost.
(b) Description of the Prior Art
One type of conventional ink-filled pen has ink filled in pen tube for the filler to absorb. The prior art usually plant the filler at the front end of pen tube to absorb ink within. However, such model makes the filler absorb ink extravagantly and easily leads to fast running out of ink, crumpled and ragged paper while exceeded ink smear over paper, and also makes ink hard to dry.
So another model of ink-filled pen with a mechanism to adjust the supply of ink to fix said disadvantages could be found in the market. However, such commonly seen ink-supply-controlled pen generally has lots of components installed at the inner front end of pen tube, therefore makes overall structure of pen complicated. It does not only lead to tedious fabrication procedure but also the difficulties to cut down manufacturing cost.
The purpose of the invention is to provide a pressure sensed ink-filled pen model comprising at least one pen tube, one valve, one filler seat, and one filler with one ink outlet installed inside the front end of said pen tube, and said U shaped soft material valve installed covering upon the front of said ink outlet inside the front end of said pen tube, by which said filler seat at the front of said pen tube with said filler pivoted constitute one pressure sensed ink-filled pen so that by pushing said filler seat and said filler, said valve could be pushed open to ensure proper measure supplement of ink. Accordingly waste of ink could be avoided and the manufacturing cost could be cut down.
The secondary purpose of the invention is to provide a pressure sensed ink-filled pen model with an end cover installed at the rear end of said pen tube by which ink within said pen tube is sealed up.
Another purpose of the invention is to provide a pressure sensed ink-filled pen model such that at the front end of the end cover a longer hollow inserting section is installed extending into the pen tube in the front, by which at the front end of said inserting section an inner stopper could be installed to reduce the space within said pen tube therefore the deposition of ink can be controlled.


A two-way book especially useful when reading to a group of young children. The book includes a binding and a plurality of pairs of pages which are movably attached to the binding. Each pair of pages has a first page and a second page with corresponding indicia thereon. Each pair of pages is also movable between an open position and a viewing position. In the open position, the first and second pages of at least one pair are substantially adjacent one another with the binding extending therebetween. In the demonstrating position, the first and second pages of one pair face opposite one another with the remaining pairs of book pages therebetween. Furthermore, the second page faces the reader of the book and the first page faces the listener of the reader so that the listener can observe the indicia as the reader reads the book. Preferably, the indicia on each page of a pair of pages is identical and includes both a text and an illustration. An alternative embodiment provides for indicia on side by side pages to be simultaneously displayed and read by the listener and reader.

Child care providers and elementary teachers are typically unable to read to the children under their care or in their class on a one on one basis. When reading to a group of young children, the children typically sit opposite and facing the reader. The reader must read the text of each page and then turn the book to face the children so that they can see the illustrations. This procedure is obviously very awkward. Furthermore, the children cannot follow the text as it is read or view the illustrations as it is read, which would both enhance their reading skills as well as their attentiveness.


A handle operator slide and a motor operator slide are individually coupled with a charging mechanism to independently charge charging springs thereof. The charging mechanism is operative to charge the springs of a contact operating mechanism as the charging springs discharge. The charging mechanism includes a prop controlled by the condition of the operating mechanism to releasably sustain the charging springs in a fully charged condition, while the operating mechanism includes a hook to releasably sustain the breaker contacts open against the urgence of fully charged operating mechanism springs. Consequently, the circuit breaker is capable of executing multiple contact opening and closing operations without recharging the charging springs by either the handle or the motor via their respective slides.

The present invention relates to circuit breakers of the industrial type which are equipped with both a manual operating handle and a motor operator mechanism to afford the capability of either local manual circuit breaker operation or typically remotely initiated motorized circuit breaker operation. Such remotely initiated operation may be effected manually (by control switch actuation) or automatically in coordination with the operations of other equipment. Thus, motor operated industrial circuit breakers have particular application as, for example, process control switches having the added benefit of affording overcurrent protection.
Heretofore, circuit breakers designed for both manual and motorized operation have typically required electrical and/or mechanical interlocking such that upon initiation of manual circuit breaker operation, motorized circuit breaker operation is locked out or defeated, and vice versa. This is done to prevent damage to the circuit breaker and possible injury to operating personnel since the circuit breaker mechanisms simply cannot tolerate concurrent manual and motorized operations. Examples of such interlocking can be found in commonly assigned U.S. Pat. Nos. 3,559,121 and 4,042,896.
Obviously, the inclusion of such interlocking adds complexity and expense to the circuit breaker design, in addition to constituting a potential source of field problems. A related problem that may be posed by this interlocking involves the possible loss of power or a malfunction in the motor operator mechanism while motorized circuit breaker operation is in process. In this event, it is highly desirable to be able to remove or defeat the interlocking such as to permit manual completion of the interrupted motorized circuit breaker operation. Defeatable interlocking, if accommodatable by the circuit breaker mechanisms, contributes further to design complexity and expense. The alternative is to await restoration of power or to remedy the source of the motor operator malfunction in order to complete the circuit breaker operation, which typically is totally unacceptable.
It is accordingly an object of the present invention to provide an improved manual and motor operated circuit breaker.
Another object of the present invention is to provide a circuit breaker of the above character, wherein manual and motor powered circuit breaker operations are accommodated in non-interfering fashion.
A further object is to provide a circuit breaker of the above character, wherein special interlocking between manual and motor powered circuit breaker operations is avoided.
Yet another object is to provide a circuit breaker of the above character, wherein circuit breaker operation initiated by the motor may be readily completed manually and vice versa.
An additional object is to provide a circuit breaker of the above character wherein the manual and motor operating means incorporated therein are efficient in design, and both convenient and reliable in operation.

Manual and motor operated circuit breaker


A flexural resonator element includes a base body and a beam with a groove and a through-hole, the beam being extended in a Y direction from the base body and flexurally vibrating in an X direction orthogonal to the Y direction, the groove being formed on a surfaces of the beam perpendicular to a Z direction orthogonal to the X direction and the Y direction, and the through-hole having a smaller width in the X direction than a width of an opening of the groove in the X direction and penetrating from an inner surface of the groove formed on the surface of the beam to a surface of the beam opposite to the surface of the beam having the groove.

1. Technical Field
The present invention relates to a flexural resonator element and a flexural resonator.
2. Related Art
In general, a flexural resonator element includes a vibrating beam. Flexural vibration of the beam causes oscillation to drive the flexural resonator element. When the flexural resonator element is driven, flexural deformation of the beam repeatedly occurs. At a certain moment, when the beam is flexurally deformed, compression displacement is caused in a region near a first side surface of the beam in a deforming direction, and expansion displacement is caused in a region near a second side surface of the beam opposite to the first side surface thereof. Thereby, at the moment, temperature in the compressed region of the beam increases, whereas temperature in the expanded region of the beam decreases. Then, at a next moment, the beam is deformed in a direction opposite to the above deforming direction, whereby the compressed region and the expanded region are switched each other.
When focusing attention on the compressed or expanded region, a cycle of increase and decrease in temperature is repeated in the region by vibration of the beam. Accordingly, when heat input or output occurs between the compressed or expanded region and another region, vibration energy of the beam is dissipated as heat energy, reducing vibration energy efficiency in the flexural resonator element. Such an energy loss is more noticeable in more compact flexural resonator elements and seems to be one of reasons why miniaturization of flexural resonator elements results in a small Q value.
To solve the problem, for example, JP-UM-A-2-032229 discloses a resonator including a hole and a groove. The hole has a same opening area both on upper and lower surfaces of a beam to allow a compressed or expanded region to be structurally independent from an other region. The groove is provided to delay the input or output of heat between the compressed or expanded region and the other region.
Miniaturization of flexural resonator elements has increasingly been demanded. To meet the demand, there is used a beam having an extremely small width. This makes it very difficult to form a groove as in the conventional art on the beam in order to increase the efficiency in the resonator element. In other words, although there is a need for formation of a narrow groove with a large depth, it is more difficult to form a narrower groove by an ordinary etching process. Additionally, mechanical strength of the beam is reduced by formation of the penetrating through-hole having the same opening area both on the upper and the lower surfaces of the beam.
Furthermore, a wiring electrode formed on the beam having a small width needs to also have a small size. This tends to cause wiring electrode breaking or unnecessary short circuit.

Flexural resonator element and flexural resonator for reducing energy loss due to heat dissipation


A model engine starter assembly is provided which is capable of quickly relieving the engagement between the actuator and the coupling pin upon the start of the model engine and includes a starter shaft which carries a starter pin and defines a shaft axis, and a hub provided with a guide groove which is slanted at a predetermined angle with respect to the shaft axis. The hub has a bore in which a rearward end portion of the starter shaft is inserted for rotational movement relative to the hub. The starter pin is received within the slanted groove so as to move the starter shaft in the direction of the shaft axis in response to rotation of the shaft axis relative to the hub to thereby move an actuator attached to a forward end of the starter shaft into and out of engagement with a connecting pin of the model engine's crank shaft. The slanted groove is defined by a front guide face which terminates at an open end of the guide groove, a rear guide face opposed to the front guide face, and a transition face which extends between the rear guide face and the open end of the guide groove.

The present invention relates to a model engine starter to be used for starting the model engine to drive a model car.
In the conventional model engine starter disclosed in Japanese Utility Model Registration No. 3093337, the sleeve (hub) is formed with a cutout having a pin actuating guide face to actuate a pin attached to the starter shaft such that said starter shaft is moved to bring a coupling member (coupling pin) mounted to the crankshaft of the model engine into engagement with an engagement recess formed in the coupling plate (drive section) so as to start the model engine.
When the model engine is started, the coupling member goes out of the engagement recess through a chamfered portion of the engagement recess to push slanting face of the coupling member such that the starter shaft is restored (moved) to the original position.
In the starter of said model engine, the sleeve is provided with a cutout having a guide face only for pushing the pin out. Therefore, it is required to make use of the chamfered portion and the slanting face in the coupling plate for restoring the starting shaft to the original position.
However, chamfering the engagement recess in the coupling plate to form a slanting face therein is so difficult that the cost is driven up.
Further, there is a need for providing a mechanism (a steel ball, a coil spring, a mounting screw or an accommodation bore) to set the initial position of the starting shaft for restoring the starting shaft to the initial position.
However, such structure requires an accommodation bore formed through the starting shaft, which can lessen the strength thereof. Further, since a bias means for retaining the rotary shaft from rotating until a predetermined load is exerted, there is a likelihood of the starting shaft rotating simultaneously with the revolution of the sleeve, making the start of the model engine impossible.
Further, the starting shaft is caused by the coupling member to rotate together with the crankshaft for some time period, generating a power loss to the model engine.


In a process for producing a magnetic metal powder, a magnetic metal compound is reduced by wet reduction in a state mixed with a clay or is heat treated in the presence of a clay powder. Alternatively, a magnetic metal powder is prepared by reducing a magnetic metal powder by wet reduction or by reducing a magnetic metal compound in a state mixed with a clay by dry reduction, and then the resulting powder is heat treated in the presence of the clay powder. The clay is typically kaolin.

This invention relates to a process for producing magnetic metal powders.
Ferromagnetic powders hitherto used in making magnetic recording media have been the powders of maghemite (.gamma.--Fe.sub.2 O.sub.3), magnetite (Fe.sub.3 O.sub.4), maghemite doped with cobalt, cobalt-doped magnetite, chromium dioxide, etc. However, as the quality requirements for magnetic recording media have recently become increasingly stringent, development of ferromagnetic powders having properties suited for higher density recording with greater sensitivity than heretofore is being called for. One of the material groups to which the developmental efforts are directed is the group of ferromagnetic metal powders, for example, of iron, cobalt, nickel, and alloys of at least two metals, including cobalt-iron and cobalt-nickel combinations.
Those ferromagnetic metal powders can be made by dry reduction, wet reduction, evaporation, thermal decomposition, and various other methods. Of those, typical methods in use on industrial scales are dry and wet reductions. Dry reduction is a general term for a variety of processes for converting ferromagnetic metal compounds by gas-phase reduction into elementary metals, including reduction with a reducing gas of the thermal decomposition product of an organic acid salt of a ferromagnetic metal, reduction with a reducing gas of an acicular oxyhydroxide which may or may not contain any of various metals or an acicular oxide obtained from such an oxyhydroxide, and reduction of an oxalate or formate of a ferromagnetic metal in a hydrogen stream. Wet reduction, on the other hand, is a technique of reducing a ferromagnetic metal salt by adding a reducing agent to a solution of the salt. In either case the powdery product obtained is customarily heat treated in order to adjust its magnetic properties, increasing its coercive force (Hc) in particular, so that the product may be suited for use in high density recording media. The heat treatment is especially important for the magnetic powder formed by wet reduction. The heat treated powder is continuously taken out of the oven into a tank, where it is impregnated with an antioxidant solvent, and then transferred to a step for producing a magnetic coating material for the manufacture of a magnetic recording medium. In that step the ferromagnetic metal powder is mixed with a binder and additives needed to prepare a magnetic coating material. The product is applied in the usual manner on a base to form a medium for magnetic recording such as a magnetic tape.
During the course of manufacture briefly outlined above, there are stages at which the magnetic metal particles being treated are heated while in contact with one another, with the possibility of the particles being aggregated or sintered together.
For example, in dry reduction, the reaction is effected by passing a reducing gas through a reactor, such as a rotary kiln, charged with a metal compound powder to be reduced. Although the reduction temperature varies with the kind of the metal compound to be reduced, the reaction at the highest temperature feasible is desired if improvements are to be attained in the magnetic properties, such as remanent magnetization and saturation magnetization, and further in productivity. On the other hand, the high treating temperature involves an increased possibility of sintering to a disadvantage. The aggregation of the particles with heat as mentioned above retards the reduction reaction. Consequently, the metal particles do not exhibit the desired magnetic properties, and the squareness ratio (SQ) of the particles as sintered is low, failing to reach the level of 0.5 or upwards required for magnetic recording media.
Similarly, the heat treatment poses the sintering problem. The heat treatment usually is conducted by a rotary kiln or an apparatus equipped with agitator blades inside and also with a heating jacket over the outer wall. The jacket heats the charge at temperatures adjustable up to 500.degree. C. The atmosphere for heat treatment is a nonoxidizing, preferably a reducing, gas atmosphere. The heat treatment time, which ranges from about one to about 30 minutes, naturally depends on the temperature. Considering the effect and efficiency of heat treatment the use of a high temperature, i.e., in the proximity of 400.degree. C., is advisable. However, the treatment at such a high temperature is accompanied with a disadvantage of an increased possibility of the magnetic metal particles being sintered. The product of dry reduction takes the form of needle-shaped particles with a major-to-minor axis ratio in the range of 5-20, whereas the particles obtained by wet reduction tend to be connected or linked like necklaces. The relatively slender particles, when exposed to a high temperature with stirring in a heat treating apparatus, easily undergo sintering, or aggregation of the particles at contacting portions.

Process for producing magnetic metal powders


A shear plate for application to the outer end portion of a ferrule to be cast into a concrete component such as a wall panel, the shear plate having an outer portion engageable with the ferrule and, beyond the outer portion, a portion shaped to incline away from the adjacent surface of the concrete component to which the outer end of the ferrule is to be exposed. The shear plate enables the ferrule to be situated close to an edge of the component in a situation in which it will be subjected to shear loading in a direction towards that edge.

Internally threaded ferrules may be incorporated into a concrete component, such as a wall panel or beam, during casting thereof to provide within the cast component a fixing point for subsequent attachment. The deep embedment of the ferrule within the concrete in conjunction with a transverse tie bar through the inner end of the ferrule and/or an enlarged base portion of the ferrule ensures that the ferrule is firmly anchored against axial loading. Provided the ferrule is sufficiently spaced from the edge of the component, the ferrule is also able to carry a substantial shear loading as a result of the inherent strength of the concrete between the ferrule and the edge of the component. That effect cannot, however, arise if the ferrule is situated relatively close to the edge of the component and in that case, ferrules have not conventionally been used in a situation where it will be subject to a shear loading in a direction towards the adjacent edge.

ITW Construction Systems Australia Pty Ltd