The present invention relates to infectious DNA clones, infectious chimeric DNA clones of porcine circovirus (PCV), vaccines and means of protecting pigs against viral infection or postweaning multisystemic wasting syndrome (PMWS) caused by PCV2. The new chimeric infectious DNA clone and its derived, avirulent chimeric virus are constructed from the nonpathogenic PCV1 in which the immunogenic ORF gene of the pathogenic PCV2 replaces a gene of the nonpathogenic PCV1, preferably in the same position. The chimeric virus advantageously retains the nonpathogenic phenotype of PCV1 but elicits specific immune responses against the pathogenic PCV2. The invention further embraces the immunogenic polypeptide expression products. In addition, the invention encompasses two mutations in the PCV2 immunogenic capsid gene and protein, and the introduction of the ORF2 mutations in the chimeric clones.

1. Field of the Invention
The present invention concerns infectious porcine circovirus type-1 (PCV1) and type-2 (PCV2) DNA clones, chimeric PCV1-2 infectious DNA clones and live chimeric viruses derived from the chimeric DNA clones, useful as vaccines. The invention further concerns two mutations in the PCV2 immunogenic capsid gene and protein, and the introduction of the ORF2 mutations in the chimeric clones.
2. Description of the Related Art
All patents and publications cited in this specification are hereby incorporated by reference in their entirety.
Porcine circovirus (PCV) was originally isolated as a noncytopathic cell culture contaminant of a porcine kidney cell line PK-15 (I. Tischer et al., "A very small porcine virus with circular single-stranded DNA," Nature 295:64-66 (1982); I. Tischer et al., "Characterization of papovavirus and picornavirus-like particles in permanent pig kidney cell lines," Zentralbl. Bakteriol. Hyg. Otg. A. 226(2):153-167 (1974)). PCV is a small icosahedral non-enveloped virus that contains a single stranded circular DNA genome of about 1.76 kb. PCV is classified in the family of Circoviridae along with other animal circoviruses such as chicken anemia virus (CAV), Psittacine beak and feather disease virus (PBFDV) and tentative members columbid circovirus (CoCV) discovered in pigeons, goose circovirus and canary circovirus, and three plant circoviruses (banana bunchy top virus, coconut foliar decay virus and subterranean clover stunt virus) (K. V. Phenix et al., "Nucleotide sequence analysis of a novel circovirus of canaries and its relationship to other members of the genus circovirus of the family Circoviridae," J. Gen. Virol. 82:2805-2809 (2001); Todd et al., "Genome sequence determinations and analyses of novel circoviruses from goose and pigeon," Virology 286:354-362 (2001); M. R. Bassami et al., "Psittacine beak and feather disease virus nucleotide sequence analysis and its relationship to porcine circovirus, plant circoviruses, and chicken anemia virus," Virology 249:453-459 (1998); J. Mankertz et al., "Transcription analysis of porcine circovirus (PCV)," Virus Genes 16:267-276 (1998); A. Mankertz et al., "Cloning and sequencing of columbid circovirus (CoCV), a new circovirus from pigeons," Arch. Virol. 145:2469-2479 (2000); B. M. Meehan et al., "Sequence of porcine circovirus DNA: affinities with plant circoviruses," J. Gen. Virol. 78:221-227 (1997); B. M. Meehan et al., "Characterization of novel circovirus DNAs associated with wasting syndromes in pigs," J. Gen. Virol. 79:2171-2179 (1998); D. Todd et al., "Comparison of three animal viruses with circular single-stranded DNA genomes," Arch. Virol. 117:129-135 (1991)).
Members of the three previously recognized animal circoviruses (PCV, CAV, and PBFDV) do not share nucleotide sequence homology or antigenic determinants with each other (M. R. Bassami et al., 1998, supra; D. Todd et al., 1991, supra). The genome of the newly identified CoCV shared about 40% nucleotide sequence identity with that of PCV (A. Mankertz et al., "Cloning and sequencing of columbid circovirus (CoCV), a new circovirus from pigeons," Arch. Virol. 145:2469-2479 (2000)). Recently, a novel human circovirus with a circular genome, designated as transfusion transmitted virus or TT virus (TTV), was identified from individuals associated with post-transfusion hepatitis (H. Miyata et al., "Identification of a novel GC-rich 113-nucleotide region to complete the circular, single-stranded DNA genome of TT virus, the first human circovirus," J. Virol. 73:3582-3586 (1999); T. Nishizawa et al., "A novel DNA virus (TTV) associated with elevated transaminase levels in posttransfusion hepatitis of unknown etiology," Biochem. Biophys. Res. Commun. 241:92-97 (1997)). Additionally, a human TTV-like mini virus (TLMV) was identified from normal blood donors (P. Biagini et al., "Genetic analysis of full-length genomes and subgenomic sequences of TT virus-like mini virus human isolates," J. Gen. Virol. 82: 379-383 (2001); K. Takahashi et al., "Identification of a new human DNA virus (TTV-like mini virus, TLMV) intermediately related to TT virus and chicken anemia virus," Arch. Virol. 145:979-93 (2000)) and a third novel human circovirus, known as SEN virus (SENV), was also discovered from humans with post-transfusion hepatitis (T. Umemura et al., "SEN virus infection and its relationship to transfusion-associated hepatitis," Hepathology 33:1303-1311 (2001)). The genomic organization of both human TTV and TLMV is similar to that of the CAV (P. Biagini et al., 2001, supra; H. Miyata et al., 1999, supra; K. Takahashi et al., 2000, supra). Although antibodies to PCV were found in various animal species including humans, mice, cattle and pigs (G. M. Allan et al., "Production, preliminary characterization and applications of monoclonal antibodies to porcine circovirus," Vet. Immunol. Immunopathol. 43:357-371 (1994); G. C. Dulac and A. Afshar, "Porcine circovirus antigens in PK-15 cell line (ATCC CCL-33) and evidence of antibodies to circovirus in Canadian pigs," Can. J. Vet. Res. 53:431-433 (1989); S. Edwards and J. J. Sands, "Evidence of circovirus infection in British pigs," Vet. Rec. 134:680-1 (1994); J. C. Harding and E. G. Clark, "Recognizing and diagnosing postweaning multisystemic wasting syndrome (PMWS)," Swine Health and Production 5:201-203 (1997); R. K. Hines and P. D. Lukert, "Porcine circovirus: a serological survey of swine in the United States," Swine Health and Production 3:71-73 (1995); G. P. Nayar et al., "Evidence for circovirus in cattle with respiratory disease and from aborted bovine fetuses," Can. Vet. J. 40:277-278 (1999); I. Tischer et al., "Distribution of antibodies to porcine circovirus in swine populations of different breeding farms," Arch. Virol. 140:737-743 (1995); I. Tischer et al., "Presence of antibodies reacting with porcine circovirus in sera of humans, mice, and cattle," Arch. Virol. 140:1427-1439 (1995)), little is known regarding the pathogenesis of PCV in these animal species. Experimental infection of pigs with the PK-15 cells-derived PCV did not produce clinical disease and thus, this virus is not considered to be pathogenic to pigs (G. M. Allan et al., "Pathogenesis of porcine circovirus; experimental infections of colostrum deprived piglets and examination of pig foetal material," Vet. Microbiol. 44:49-64 (1995); I. Tischer et al., "Studies on epidemiology and pathogenicity of porcine circovirus," Arch. Virol. 91:271-276 (1986)). The nonpathogenic PCV derived from the contaminated PK-15 cell line was designated as porcine circovirus type 1 or PCV1.
Postweaning multisystemic wasting syndrome (PMWS), first described in 1991 (J. C. Harding and E. G. Clark, 1997, supra), is a complex disease of weaning piglets that is becoming increasingly more widespread. With the threat of a potential serious economic impact upon the swine industry, it has become urgent to develop a vaccine against PCV2, the primary causative agent of PMWS. PMWS mainly affects pigs between 5-18 weeks of age. Clinical PMWS signs include progressive weight loss, dyspnea, tachypnea, anemia, diarrhea, and jaundice. Mortality rate may vary from 1% to 2%, and up to 40% in some complicated cases in the U.K. (M. Muirhead, "Sources of information on PMWS/PDNS," Vet. Rec. 150:456 (2002)). Microscopic lesions characteristic of PMWS include granulomatous interstitial pneumonia, lymphadenopathy, hepatitis, and nephritis (G. M. Allan and J. A. Ellis, "Porcine circoviruses: a review," J. Vet. Diagn. Invest. 12:3-14 (2000); J. C. Harding and E. G. Clark, 1997, supra). PMWS has now been recognized in pigs in Canada, the United States (G. M. Allan et al., "Novel porcine circoviruses from pigs with wasting disease syndromes," Vet. Rec. 142:467-468 (1998); G. M. Allan et al., "Isolation of porcine circovirus-like viruses from pigs with a wasting disease in the USA and Europe," J. Vet. Diagn. Invest. 10:3-10 (1998); G. M. Allan and J. A. Ellis, 2000, supra; J. Ellis et al., "Isolation of circovirus from lesions of pigs with postweaning multisystemic wasting syndrome," Can. Vet. J. 39:44-51 (1998); A. L. Hamel et al., "Nucleotide sequence of porcine circovirus associated with postweaning multisystemic wasting syndrome in pigs," J. Virol. 72:5262-5267 (1998); M. Kiupel et al., "Circovirus-like viral associated disease in weaned pigs in Indiana," Vet. Pathol. 35:303-307 (1998); R. Larochelle et al., "Identification and incidence of porcine circovirus in routine field cases in Quebec as determined by PCR," Vet. Rec. 145:140-142 (1999); B. M. Meehan et al., 1998, supra; I. Morozov et al., "Detection of a novel strain of porcine circovirus in pigs with postweaning multisystemic wasting syndrome," J. Clin. Microbiol. 36:2535-2541 (1998)), most European countries (G. M. Allan et al., "Isolation of porcine circovirus-like viruses from pigs with a wasting disease in the USA and Europe," J. Vet. Diagn. Invest. 10:3-10 (1998); G. M. Allan and J. A. Ellis, 2000, supra; S. Edwards and J. J. Sands, 1994, supra; S. Kennedy et al., "Porcine circovirus infection in Northern Ireland," Vet. Rec. 142:495-496 (1998); A. Mankertz et al., "Characterization of PCV-2 isolates from Spain, Germany and France," Virus Res. 66:65-77 (2000); C. Rosell et al., "Identification of porcine circovirus in tissues of pigs with porcine dermatitis and nephropathy syndrome. Vet. Rec. 146:40-43 (2000); P. Spillane et al., "Porcine circovirus infection in the Republic of Ireland," Vet. Rec. 143:511-512 (1998); G. J. Wellenberg et al., "Isolation and characterization of porcine circovirus type 2 from pigs showing signs of post-weaning multisystemic wasting syndrome in the Netherlands," Vet. Quart. 22:167-72 (2000)) and some countries in Asia (C. Choi et al., "Porcine postweaning multisystemic wasting syndrome in Korean pig: detection of porcine circovirus 2 infection by immunohistochemistry and polymerase chain reaction," J. Vet. Diagn. Invest. 12:151-153 (2000); A. Onuki et al., "Detection of porcine circovirus from lesions of a pig with wasting disease in Japan," J. Vet. Med. Sci. 61:1119-1123 (1999)). PMWS potentially has a serious economic impact on the swine industry worldwide.
The primary causative agent of PMWS is a pathogenic strain of PCV designated as porcine circovirus type 2 or PCV2 (G. M. Allan et al., "Novel porcine circoviruses from pigs with wasting disease syndromes," Vet. Rec. 142:467-468 (1998); G. M. Allan et al., "Isolation of porcine circovirus-like viruses from pigs with a wasting disease in the USA and Europe," J. Vet. Diagn. Invest. 10:3-10 (1998); G. M. Allan et al., "Isolation and characterisation of circoviruses from pigs with wasting syndromes in Spain, Denmark and Northern Ireland," Vet. Microbiol. 66:115-23 (1999); G. M. Allan and J. A. Ellis, 2000, supra; J. Ellis et al., 1998, supra; A. L. Hamel et al., 1998, supra; B. M. Meehan et al., 1998, supra; I. Morozov et al., 1998, supra). The complete genomic sequence of the PMWS-associated PCV2 and nonpathogenic PCV1 have been determined (R. Larochelle et al., "Genetic characterization and phylogenetic analysis of porcine circovirus type 2 (PCV2) strains from cases presenting various clinical conditions," Virus Res. 90:101-112 (2002); M. Fenaux et al., "Genetic characterization of type 2 porcine circovirus (PCV-2) from pigs with postweaning multisystemic wasting syndrome in different geographic regions of North America and development of a differential PCR-restriction fragment length polymorphism assay to detect and differentiate between infections with PCV-1 and PCV-2," J. Clin. Microbiol. 38:2494-503 (2000); A. L. Hamel et al., 1998, supra; J. Mankertz et al., 1998, supra; B. M. Meehan et al., 1997, supra; B. M. Meehan et al., 1998, supra; I. Morozov et al., 1998, supra).
PCV1 is ubiquitous in pigs but is not pathogenic to pigs. In contrast, the genetically related PCV2 is pathogenic and causes PMWS in pigs. Sequence analyses reveals that the PMWS-associated PCV2 typically shares only about 75% nucleotide sequence identity with the nonpathogenic PCV1. Some other strains may vary somewhat to about 74% to about 76% nucleotide sequence identity. Both PCV1 and PCV2 have a very similar genomic organization and are small, non-enveloped viruses with a single stranded circular DNA genome of about 1.76 kb. The PCV genome contains at least two functional open reading frames (ORFs): ORF1 (930 bp) encodes the Rep proteins involved in viral replication (A. K. Cheung, "Transcriptional analysis of porcine circovirus," Virology 305: 168-180 (2003)) and ORF2 (699 bp) encodes the major immunogenic viral capsid protein (A. K. Cheung, 2003, supra; P. Nawagitgul et al., "Modified indirect porcine circovirus (PCV) type 2-based and recombinant capsid protein (ORF2)-based ELISA for the detection of antibodies to PCV," Immunol. Clin. Diagn. Lab Immunol. 9(1):33-40 (January 2002); P. Nawagitgul et al., "Open reading frame 2 of porcine circovirus type 2 encodes a major capsid protein," J. Gen. Virol. 81:2281-2287 (2000)).
Initial attempts to reproduce clinical PMWS in conventional pigs by PCV2 inoculation were unsuccessful (M. Balasch et al., "Experimental inoculation of conventional pigs with tissue homogenates from pigs with post-weaning multisystemic wasting syndrome," J. Comp. Pathol. 121:139-148 (1999); M. Fenaux et al., "Cloned Genomic DNA of Type 2 Porcine Circovirus (PCV-2) Is Infectious When Injected Directly into the Liver and Lymph Nodes of SPF Pigs: Characterization of Clinical Disease, Virus Distribution, and Pathologic Lesions," J. Virol. 76:541-551 (2002)). Experimental reproduction of clinical PMWS in gnotobiotic pigs and conventional pigs with tissue homogenates from pigs with naturally occurring PMWS and with cell culture propagated PCV2 produced mixed results. Clinical PMWS was reproduced in gnotobiotic (SPF) pigs and colostrum-deprived and caesarian-derived pigs co-infected with PCV2 and porcine parvovirus (PPV) (G. M. Allan et al., "Experimental reproduction of severe wasting disease by co-infection of pigs with porcine circovirus and porcine parvovirus," J. Comp. Pathol. 121:1-11 (1999); S. Krakowka et al., "Viral wasting syndrome of swine: experimental reproduction of postweaning multisystemic wasting syndrome in gnotobiotic swine by coinfection with porcine circovirus 2 and porcine parvovirus," Vet. Pathol. 37:254-263 (2000)), and in PCV2-inoculated gnotobiotic pigs when their immune system was activated by keyhole hemocyanin in incomplete Freund's adjuvant (S. Krakowka et al., "Activation of the immune system is the pivotal event in the production of wasting disease in pigs infected with porcine circovirus-2 (PCV-2)," Vet. Pathol. 38:31-42 (2001)).
Clinical PMWS was also reproduced in cesarean derived/colostrum deprived pigs (CD/CD) inoculated with PCV2 alone (P. A. Harms et al., "Experimental reproduction of severe disease in CD/CD pigs concurrently infected with type 2 porcine circovirus and porcine reproductive and respiratory syndrome virus," Vet. Pathol. 38:528-539 (2001)) and in conventional pigs co-infected with PCV2 and either porcine parvovirus (PPV) or porcine reproductive and respiratory syndrome virus (PRRSV) (A. Rivora et al., "Experimental inoculation of conventional pigs with porcine reproductive and respiratory syndrome virus and porcine circovirus 2," J. Virol. 76: 3232-3239 (2002)). In cases of the PRRSV/PCV2 co-infection, the PMWS characteristic pathological signs such as lymphoid depletion, granulomatous inflammation and necrotizing hepatitis are induced by PCV2 and not by PRRSV (P. A. Harms et al., 2001, supra). However, clinical PMWS was not reproduced in gnotobiotic pigs infected with PCV2 alone (G. M. Allan et al., "Experimental infection of colostrums deprived piglets with porcine circovirus 2 (PCV2) and porcine reproductive and respiratory syndrome virus (PRRSV) potentiates PCV2 replication," Arch. Virol. 145:2421-2429 (2000); G. M. Allan et al., "A sequential study of experimental infection of pigs with porcine circovirus and porcine parvovirus: immunostaining of cryostat sections and virus isolation, J. Vet. Med. 47:81-94 (2000); G. M. Allan et al., "Experimental reproduction of severe wasting disease by co-infection of pigs with porcine circovirus and porcine parvovirus," J. Comp. Pathol. 121:1-11 (1999); M. Balasch et al., 1999, supra; J. Ellis et al., "Reproduction of lesions of postweaning multisystemic wasting syndrome in gnotobiotic piglets," J. Vet. Diagn. Invest. 11:3-14 (1999); S. Kennedy et al., "Reproduction of lesions of postweaning multisystemic wasting syndrome by infection of conventional pigs with porcine circovirus type 2 alone or in combination with porcine parvovirus" J. Comp. Pathol. 122:9-24 (2000); S. Krakowka et al., 2001, supra; S. Krakowka et al., 2000, supra; R. M. Pogranichnyy et al., "Characterization of immune response of young pigs to porcine circovirus type 2 infection," Viral. Immunol. 13:143-153 (2000)). The virus inocula used in these studies were either homogenates of tissues from pigs with naturally occurring PMWS, or virus propagated in PK-15 cell cultures (G. M. Allan et al., "Experimental infection of colostrums deprived piglets with porcine circovirus 2 (PCV2) and porcine reproductive and respiratory syndrome virus (PRRSV) potentiates PCV2 replication," Arch. Virol. 145:2421-2429 (2000); G. M. Allan et al., "A sequential study of experimental infection of pigs with porcine circovirus and porcine parvovirus: immunostaining of cryostat sections and virus isolation, J. Vet. Med. 47:81-94 (2000); G. M. Allan et al., "Experimental reproduction of severe wasting disease by co-infection of pigs with porcine circovirus and porcine parvovirus," J. Comp. Pathol. 121:1-11 (1999); M. Balasch et al., 1999, supra; J. Ellis et al., 1999, supra; S. Kennedy et al., 2000, supra; S. Krakowka et al., 2001, supra; S. Krakowka et al., 2000, supra; R. M. Pogranichnyy et al., 2000, supra). Since tissue homogenates may contain other common swine agents such as PPV and porcine reproductive and respiratory syndrome virus (PRRSV) (G. M. Allan et al., "Experimental infection of colostrums deprived piglets with porcine circovirus 2 (PCV2) and porcine reproductive and respiratory syndrome virus (PRRSV) potentiates PCV2 replication," Arch. Virol. 145:2421-2429 (2000); G. M. Allan et al., "Experimental reproduction of severe wasting disease by co-infection of pigs with porcine circovirus and porcine parvovirus," J. Comp. Pathol. 121:1-11 (1999); G. M. Allan and J. A. Ellis, 2000, supra; J. A. Ellis et al., "Coinfection by porcine circoviruses and porcine parvovirus in pigs with naturally acquired postweaning multisystemic wasting syndrome," J. Vet. Diagn. Invest. 12:21-27 (2000); C. Rosell et al., 2000, supra), and since the ATCC PK-15 cell line used for PCV2 propagation was persistently infected with PCV1 (G. C. Dulac and A. Afshar, 1989, supra), the clinical disease and pathological lesions reproduced in those studies may not be solely attributable to PCV2 infection (G. M. Allan et al., "Experimental infection of colostrums deprived piglets with porcine circovirus 2 (PCV2) and porcine reproductive and respiratory syndrome virus (PRRSV) potentiates PCV2 replication," Arch. Virol. 145:2421-2429 (2000); G. M. Allan et al., "A sequential study of experimental infection of pigs with porcine circovirus and porcine parvovirus: immunostaining of cryostat sections and virus isolation, J. Vet. Med. 47:81-94 (2000); G. M. Allan et al., "Experimental reproduction of severe wasting disease by co-infection of pigs with porcine circovirus and porcine parvovirus," J. Comp. Pathol. 121:1-11 (1999); G. M. Allan and J. A. Ellis, 2000, supra; J. A. Ellis et al., 2000, supra).
Clinical PMWS has also been reproduced in PCV2-inoculated CDCD pigs when vaccinated with Mycoplasma hyopneumoniae (G. M. Allan et al., "Immunostimulation, PCV-2 and PMWS," Vet. Rec. 147:171-172 (2000)). Two recent field studies by G. M. Allan et al., "Neonatal vaccination for Mycoplasma hyopneumoniae and postweaning multisystemic wasting syndrome: a field trial," Pig J. 48:34-41 (2001), and S. C. Kyriakis et al., "The effects of immuno-modulation on the clinical and pathological expression of postweaning multisystemic wasting syndrome," J. Comp. Pathol. 126:38-46 (2002), tested the effect of immuno-modulation by Mycoplasma hyopneumoniae vaccine on the development of PMWS in endemic herds, and showed a significant decrease in PMWS cases in unvaccinated groups compared to the vaccinated animals. However, another recent study using conventional SPF piglets under controlled laboratory conditions could not reproduce such an effect, suggesting that vaccinations with M. hyopneumoniae may potentially influence the development of clinical PMWS but it is clearly a secondary role to a PCV2 infection. Based on these and other studies, PCV2 is nevertheless considered to be the primary but not the exclusive causative agent of PMWS.
The lack of an infectious virus stock of a biologically pure form of PCV2 has impeded the understanding of PCV2 pathogenesis and the etiological role of PCV2 in PMWS. Vaccinations against PPV and possibly PRRSV have not consistently been shown to prevent the onset of PMWS in PCV2 infected pigs. Consequently, finding a safe yet potent vaccine that specifically targets PMWS has been difficult. There is a definite art-recognized need in the veterinary field to produce an efficacious, safe vaccine against PCV2 infections and PMWS.
U.S. Pat. No. 6,287,856 (Poet et al.) and WO 99/45956 concern nucleic acids from psittacine beak and feather disease virus (BFDV), a circovirus that infects avian species, and from porcine circovirus (PCV). The patent proposes vaccine compositions comprising naked DNA or mRNA and discloses a nucleic acid vector for the transient expression of PCV in a eukaryotic cell comprising a cis-acting transcription or translation regulatory sequence derived from the human cytomegalovirus immediate or early gene enhancer or promoter functionally linked to a nucleic acid of the sequence. However, since the PCV DNA is derived solely from the PK-15 cell line, it is likely to comprise the nonpathogenic PCV1 discovered nearly 30 years ago by I. Tischer et al., 1974, supra, and, therefore, it is not likely to be effective in eliciting an immune reaction to PCV2 or infections caused by PCV2. Subunit vaccines of recombinant proteins made from vectors comprising open reading frames are also suggested in the patent but the open reading frames from PCV are not well characterized or distinguished from each other. Since the source of the PCV DNA is PK-15 cells, the proteins made from those vectors comprising the open reading frames of PCV1 would not possess reliable immunogenic properties, if any, against PCV2.
U.S. Pat. No. 6,217,883 (Allan et al.) and French Patent No. 2,781,159B relate to the isolation of five PCV strains from pulmonary or ganglionic samples taken from pigs infected with PMWS in Canada, California and France (Brittany), and their use in combination with at least one porcine parvovirus antigen in immunogenic compositions. Proteins encoded by PCV2 open reading frames (ORF) consisting of ORF1 to ORF13 are broadly described in the patent but there is no exemplification of any specific protein exhibiting immunogenic properties. The patent further discloses vectors consisting of DNA plasmids, linear DNA molecules and recombinant viruses that contain and express in vivo a nucleic acid molecule encoding the PCV antigen. Several other references, for example, U.S. Pat. No. 6,391,314 B1; U.S. Pat. No. 6,368,601 B1; French Patent No. 2,769,321; French Patent No. 2,769,322; WO 01/96377 A2; WO 00/01409; WO 99/18214; WO 00/77216 A2; WO 01/16330 A2; WO 99/29871; etc., also describe the administration of PCV1 or PCV2 polypeptides or the nucleic acids encoding the polypeptides of various strains.
However, the nonpathogenic PCV1 will not be useful against PCV2 infections and the pathogenic PCV2 strains described in the art, even if attenuated, are likely to be of limited value due to the usual tendency of a live virus to revert to its virulent state. Therefore, there is still a long-standing need in the art for a live, infectious, nonpathogenic antigen for the inoculation of pigs against serious infection or PMWS caused by PCV2 that is efficacious and remains safe in veterinary vaccines. These goals are met by the construction of the new live chimeric porcine circovirus described herein, which is based upon the genomic backbone of the nonpathogenic PCV1 isolated by I. Tischer et al. almost 30 years ago. The novel chimeric porcine circovirus of the present invention is able to satisfy that long-standing need by uniquely and advantageously retaining the nonpathogenic phenotype of PCV1 but eliciting specific immune response against pathogenic PCV2.
PCV2 causes pathological lesions characteristic of PMWS in specific-pathogen-free (SPF) pigs whereas PCV1 does not (M. Fenaux et al., 2002, supra). Based on the current studies, it is also observed that cell culture-derived PCV1 replicates more efficiently in PK-15 cells than PCV2 (see also M. Fenaux et al., "Immunogenicity and pathogenicity of the chimeric infectious DNA clones between pathogenic type 2 porcine circovirus (PCV2) and non-pathogenic PCV1 in weaning pigs," J. Virol. 77:11232-11243 (2003)). However, the genetic determinants for PCV2 pathogenicity in pigs and for the enhanced growth ability of PCV1 in PK-15 cells are not known. Thus, another set of objectives of the present invention is to identify and characterize the genetic determinants for PCV2 pathogenicity in vivo and for replication in vitro.

Chimeric infectious DNA clones, chimeric porcine circoviruses and uses thereof

Virginia Tech Intellectual Properties, Inc.

Iowa State University Research Foundation, Inc.


A vacuum brake booster having a vacuum chamber and a working chamber, which are separated from one another by a movable wall, and a control valve is described. The control valve has a control valve housing (10), which is coupled workingly to the movable wall and which, for achieving a pressure difference at the movable wall, is capable of controlling the supply of atmospheric pressure or above-atmospheric pressure to the working chamber in dependence upon the displacement of an input element of the vacuum brake booster. The control valve housing (10) comprises an outer sleeve (12) and an inner sleeve (48), which is disposed radially at the inside of and coaxially with the outer sleeve (12) and is connected by a plurality of webs (58, 62) to the outer sleeve (12). The control valve housing (10) is manufactured by injection molding, wherein at least one injection point (42) is provided, which is disposed in the region of the outer sleeve (12) and at a distance from fastening points of the webs (58, 62) to the outer sleeve (12).

The invention relates to a vacuum brake booster, having a vacuum chamber and a working chamber separated from one another by a movable wall, and a control valve which comprises a control valve housing coupled workingly to the movable wall and which, for achieving a pressure difference at the movable wall, is capable of controlling the supply of atmospheric pressure or above-atmospheric pressure to the working chamber in dependence upon the displacement of an input element of the vacuum brake booster, wherein the control valve housing comprises an outer sleeve and an inner sleeve, which is disposed radially at the inside of and coaxially with the outer sleeve and is connected by a plurality of webs to the outer sleeve.
Such a vacuum brake booster in tandem-design is known from DE-OS 24 36 144, and corresponding U.S. Pat. No. 3,897,718 which is incorporated by reference herein. In accordance with the tandem design, a housing of the vacuum brake booster is divided by stationary walls into two separate housing portions each of a fixed volume. Each of said two separate housing portions is subdivided by a movable wall into a vacuum chamber and a working chamber. Altogether, the vacuum brake booster known from DE-OS 24 36 144 comprises two movable walls, which are disposed inside the housing of the vacuum brake booster and coupled rigidly to a control valve housing.
Given a movement of the control valve housing relative to the housing of the vacuum brake booster, vacuum-tight guidance of the control valve housing has to be guaranteed. For said reason, an outer sleeve of the control valve housing has radially at the outside two axially offset sliding surfaces, on each of which a ring seal sealing a stationary wall in the direction of the control valve housing slides.
The outer sleeve is connected by a plurality of webs to an inner sleeve so as to produce an air flow path between outer sleeve and inner sleeve. The inner sleeve functions as a guide for an actuating piston, which is coupled to the input element of the vacuum brake booster and cooperates via a cylindrical sensing element with an elastomer reaction disk. The actuating forces, which the actuating piston introduces into the reaction disk by means of the sensing element and which are summoned up by the driver, are transmitted from the reaction disk to a reaction piston. Besides the actuating forces, the booster forces attributable to the displacement of the movable walls coupled to the control valve housing are additionally introduced into the reaction disk by means of an end face coupled to the inner sleeve. The booster forces are transmitted from the outer sleeve of the control valve housing by means of the plurality of webs to the inner sleeve.


Examples disclosed herein relate to receiving a request to perform an operation on a document, determining whether the document complies with a plurality of operation policies, and in response to determining that the document complies with the plurality of operation policies, providing a notification that the operation is ready to be performed and digitally signing the document.

Users often desire to print documents at a printing device. Typically, printer drivers convert the document data to a form specific to each printer, such that applications need not be aware of the technical details of each printer model. Modern operating systems often support both model-specific print drivers for individual printers and universal print drivers that may be capable of converting data to printer specific formats for a multitude of printer models.

Hewlett-Packard Development Company, L.P.


The present disclosure discloses an optical imaging lens assembly. The optical imaging lens assembly includes: a first lens, a second lens, a third lens, a fourth lens, a fifth lens, a sixth lens and a seventh lens in sequence from an object side to an image side along an optical axis. The first lens, the second lens, and the sixth lens each have a positive refractive power. The third lens and the seventh lens each have a negative refractive power. The fourth lens and the fifth lens each have a refractive power. Object-side surfaces of the first lens and the second lens are both convex surfaces. An image-side surface of the third lens is a concave surface. A total effective focal length f of the optical imaging lens assembly and a radius of curvature R13 of an object-side surface of the seventh lens satisfy: |f/R13|≥2.5.

As portable electronic products update rapidly, higher requirements are put forward on the matching imaging lens assemblies. The trend of miniaturization of the portable electronic products requires ultra-thin miniaturization of the imaging lens assemblies. At the same time, with the application and popularization of portable electronic products such as mobile phones or tablet computers, the matching imaging lens assemblies need to nave a good imaging quality not only under conditions such as daylight or sufficient lighting, but also under insufficient lighting conditions such as cloudy days or at dusk. Thus, corresponding requirements on the high pixel, high resolution, brightness of the image plane and clear aperture of the imaging lens assemblies is raised.


One example includes a method of attributing revenue to keywords for an entity having an entity website. The method may include obtaining the keywords used in a secured search on a search engine that result in a visit to an entity website and determining a position or rank of a webpage of the website on a search results page resulting from searching the keyword. The method may further include estimating, based on the rank of the webpage, a number of visits to the website that result from secured searches of the keyword.

Search engine optimization (SEO) generally describes the use of computing systems for running computing processes that collect, store, and analyze search engine data in order to provide recommendations to improve visibility of a website or a webpage in search engines. Search engine results can be obtained by one or more search strategies, such as natural, un-paid, organic, or algorithmic search results as well as for paid search algorithms of search engine marketing (SEM) target paid listings. Generally, the higher a website is located on a website listing and the more frequently a website appears in the search results list, the more visitors it will receive from the search engine's users.
SEO is implemented by Internet Technology (IT) professionals to improve the volume and quality of traffic to a given webpage or other Internet site. Typical techniques include keywords in title tags, keywords in meta tags, keywords in body text, anchor text in inbound links, age of site, site structure, link popularity in a site's internal link structure, amount of indexable text/page content, number of links to a site, popularity/relevance of links to site and topical relevance of inbound link tags, any of which can include SEO data. Additional techniques are sometimes employed based on the search engine for which the webmaster is attempting to optimize. Since search engine algorithms and metrics are proprietary as opposed to publicly available, search engine optimization techniques including the use of algorithms and metrics in conjunction with a computer or computing system are widely used to improve visibility of a webpage or other Internet site on search engine result pages. Entities, such as companies and individuals, may employ SEO to improve the volume and quality of traffic to their websites to increase sales, brand recognition, dissemination of their product, advertising, or for any other purpose.
Recent transitions by search engines include increased use of an encryption protocol called Secure Sockets Layer (SSL) in order to adopt stronger security standards. SSL and its predecessor Transport Layer Security (TLS) are useful in preventing eavesdropping and tampering of users' communication across a network. Hypertext Transfer Protocol (HTTP) is a widely used networking protocol for the World Wide Web. Hypertext Transfer Protocol Secure (HTTPS) is a combination of HTTP with SSL/TLS protocol to provide encrypted communication and secure identification of a network web server.
The subject matter claimed herein is not limited to embodiments that solve any disadvantages or that operate only in environments such as those described above. Rather, this background is only provided to illustrate one exemplary technology area where some embodiments described herein may be practiced.

This patent is subject to a terminal disclaimer.

Search engine optimization with secured search


A memory system connected to a processor is described. The memory system includes a volatile first storage section, a nonvolatile second storage section having a smaller storage capacity than that of the first storage section, and a storage control section that performs control to store data sets in the second storage section. Each of the data sets including data written in the first storage section in response to a write command from the processor, address information indicating a write destination in the first storage section, and address information indicating a write destination in a nonvolatile third storage section to which the data written in the first storage section is to be written back.

A highly reliable main memory that safely holds data in a main memory even when unexpected power loss occurs is generally called a persistent memory. An NVDIMM (Non-Volatile Dual Inline Memory Module) is formulated as standard related to this type of memory.
The NVDIMM includes a DRAM (Dynamic Random Access Memory) used as a main memory, a backup power supply for DRAM, a NAND flash memory, and a memory controller for NVDIMM. When the power supply of the NVDIMM is lost, data in the DRAM is saved in the NAND flash memory by using the backup power supply. The backup power supply is configured with a battery, a super capacitor and the like. The mounting area of the backup power supply hinders miniaturization of the system, and the cost of parts is increased by providing the backup power supply.
If a high-speed nonvolatile memory such as a MRAM (Magnetoresistive RAM) is used as the main memory instead of a DRAM, a backup power supply is unnecessary, but in a high-speed nonvolatile memory, the miniturization of a memory cell is difficult, and a bit unit price is higher than that of a DRAM, thus, it is not suitable for general applications.


The invention relates to an automated system for adjusting line array speakers. The automated system includes a system for moving two or more speakers with a moving device. Additionally, moving two linear actuators essentially simultaneously; a bracket to attach to the moving device to the speaker; a remote control system for controlling the movement of the speakers and for displaying the position of the speakers in real time; and a system for modeling and determining the proper frequency response for a venue and automatically adjusting the linear array speaker systems to the proper position for the proper frequency response.

1. Field of the Invention
This invention relates to a system of moving line array speakers, including a system to allow two linear actuators to move essentially simultaneously, a bracket to support the array, a remote control to move the actuators and a method of testing the frequency response of a line arrays in a venue and automatically adjusting the line arrays to achieve the optimum frequency response.
2. Discussion of the Related Art
The entertainment industry is one of the largest grossing industries in the world and audio systems are used to support this industry for theatrical productions, concerts, and movies. The audio systems are typically high-end speaker systems because high fidelity sound is required to ensure the audience receives the highest quality audio experience during an event.
Previous speaker systems are stacked up from the floor to achieve a specific height above the audience to create the proper frequency response. A proper frequency response allows every member of the audience to hear the event with the same clarity. Additionally, problems such as echo and distortion are created due to obstacles in the venue (i.e. columns) or the improper placement of the speakers in the system.
Problems with the stacking arrangement are that the speaker systems can only be stacked to a certain height and the stacked height may not be the height required to achieve the proper frequency response for the entire venue. The speakers were always set to the same angle, and thus were very difficult to adjust the frequency response.
Technology to correct some of the shortcomings of the floor stacked speaker system is a line array speaker system. The line array speaker system can either be suspended from the ceiling of a venue or stacked on the floor. The line array speaker system allows for even frequency response over large areas.
The speakers within the line array acoustically couple with each other depending on the angles that separate the individual speakers. Changing the angles between the speakers can control this coupling affect, which in turn, allows the user of the line array extensive control over the frequency response of the system. Currently, changing the angle between the speakers must be done by hand at ground level.
When a line array system is set up, metal spacers must be placed between the speakers to allow the user to create angles that would best suit the speaker placement in the venue. The angles are set in relation to the speaker below it. Thus, if the angle of the top most speaker requires an adjustment, every speaker in the array must be adjusted.
Currently, a line array is assembled by "stacking" speakers in a vertical column. Each speaker can weigh between approximately 100 and 500 pounds. The array is assembled and the angle between each speaker in the array is set. The frequency response of the line array is then tested. If the frequency response requires adjustment, the spacing between the speakers must be adjusted. Depending on which speaker requires adjustment, the entire array must be dissembled and reassembled with the new spacing. The above process is repeated until the proper frequency response for the venue is achieved. This trial and error process requires time and man power. The time and labor required adds additional costs to events. Additionally, since the line arrays are designed to be suspended, additional time is required to raise and lower the array in order to make the necessary adjustments.
Previously, the angles for each venue were determined once the line array system was in place at the venue. Presently, angle measurements can be determined, using software, prior to arriving at a venue, for example, MAPP (Multifunctional Acoustical Prediction Program) Online™ by Meyer Sound Laboratories. The software can be programmed to model acoustical aspects of a venue, while simulating the affects of angle changes within a line array. Most software can only simulate a sectional view of a venue, and it cannot take into consideration obstacles that project from the side of a theater or hall. The software allows a user to acquire basic angle estimates, but cannot be used to make precise angle adjustments within a venue. The precision adjustments must still be done, by trial and error, according to the requirements of the venue in which the array is arranged. Currently, no systems are available that computer models the venue in real time with the line arrays in position.
Thus, there is a need in the art for remote controlled system that can adjust the angles between individual speakers in a line array without having to disassemble the array and also while the speaker array is suspended from the ceiling. Additionally, there is a need in the art for an automated system to model and adjust the line arrays, in the actual venue, with minimum human intervention.

Automated system for adjusting line array speakers


An information output device is provided, which includes a request acquisition unit that acquires a maintenance request for a vehicle; a user information acquisition unit that acquires information regarding each of a plurality of users; a message generator that generates a message associated with the maintenance request acquired by the request acquisition unit; and a message output unit that outputs the message generated by the message generator. The user information acquisition unit acquires maintenance records of the vehicle that are records of maintenance executed for the vehicle by the plurality of users. The message generator selects a presentation destination user to be presented with the message and generates the message based on a maintenance record of the presentation destination user among the maintenance records of the vehicle. The maintenance record of the presentation destination user is a record of the maintenance executed by the presentation destination user.

A vehicle that expresses emotions is known, which is configured to be capable of executing external charging for an onboard battery with electric power from outside the vehicle (e.g., Patent Document 1). The vehicle described in Patent Document 1 includes an operation device and a control device. The control device makes a notification for prompting the user to execute the external charging when the SOC of the battery is a predetermined value or less. Then, when the user executes the external charging after the notification, the control device controls the operation device to execute a first operation (e.g., an operation corresponding to an emotion such as a sense of joy or appreciation). On the other hand, when the user does not execute the external charging after the notification, the control device controls the operation device to execute a second operation (e.g., an operation corresponding to an emotion such as a sense of desolation or dissatisfaction) different from the first operation.

Information output device and information output method


The present invention relates to a coating composition using a catalyst for selective catalytic reduction for the removal of nitrogen oxides from the exhaust gas, a catalytic module element for selective catalytic reduction and a catalytic module for selective catalytic reduction for the removal of nitrogen oxides, and more specifically to a catalytic module element in which and a catalytic module element for selective catalytic reduction in which a plurality of plate-type or waveform glass fiber sheets on which the coating layer of a catalyst for selective catalytic reduction are formed, are repeatedly laminated and a catalytic module for casing the catalytic module element. According to the present invention, the production process is simple, economical and productive and the catalytic module element for selective catalytic reduction is excellent not only in decomposition efficiency of nitrogen oxides in the exhaust gas, but also in durability, economic efficiency and thermal shock resistance. Further, the present invention has an advantage capable of providing a catalytic module that can be used in an operation by directly placing it on the actual spot.

Nitrogen oxides (NOx), which are exhaust gases produced from a power station using, as a main fuel, coal, heavy oil and gas, is the main culprit of air pollution and much cost is required for treating the NOx gas.
When nitrogen oxides are decomposed with a catalyst for high efficiency selective catalytic reduction (SCR), which is one of catalysts for the removal of nitrogen oxides, air pollution can be efficiently reduced with a low cost.
The catalyst for selective catalytic reduction (SCR catalyst) mainly comprises a support such as titania, alumina, silica and zirconia, and oxides of active metals such as vanadium, molybdenum, nickel, tungsten, iron and copper. In particular, the commercial selective catalytic reduction techniques mostly deal with V2O5/TiO2 catalysts. Further, various SCR catalysts for the removal of nitrogen oxides from exhaust gases are known in several patent documents including Korean Patent Nos. 382051, 473080 and 275301.
The process of selective catalytic reduction (SCR) has been used for a long time in the power station sector to remove the nitrogen oxides from exhaust gases. Herein, ammonia (NH3) is introduced into exhaust gases and is selectively reacted with the nitrogen oxides on a suitable catalyst to obtain nitrogen and water.
In the past, a method for manufacturing the most generally known catalytic module element in connection with selective catalytic reduction (SCR) techniques includes wash coating and extrusion.
The wash coating is a technique that is used in manufacturing a catalytic converter used as an automobile exhaust emission control system and in which a catalyst is thinly coated on the surface of a cordierite in the form of honeycomb (grid-type square brick form). However, this process is difficult to mass-produce a catalyst since the whole operation is manually performed in the selective catalytic reduction for many stationary sources and is not economical in that expensive cordierite is used as the support and hence the competitive price is lower than a process directly extruding an inexpensive catalyst.
Meanwhile, the extrusion generally uses a honeycomb produced through an extrusion manner by converting SCR powders into a highly viscous liquid phase. However, the honeycomb produced through the extrusion manner has problems in that is heavy and there are cracks in a molded article during drying and baking of the molded and extruded product, it is not economic because longer times are required in baking, and physical strength is lowered. In other words, cracks are generated because an exothermic reaction occurs in a drying step of a catalyst and thus an organic binder is suddenly volatilized. Further, the extrusion has problems in that the removal efficiency of nitrogen oxides is low and various types of catalytic module elements cannot be manufactured.

Composition, catalytic module element, and catalytic module for selective catalytic reduction of nitrogen oxides in gaseous medium containing oxygen


A filter frame and media capable of withstanding repeated heating to high temperatures in an oxidizing environment, and a method of cleaning the same for indefinite use in a method of operating industrial paint booths. Progressive density, heat resistant, and preferably metal media paint booth filters are provided for replacement of existing filters in industrial paint booths. The filters are structurally resistant to cyclic heating to high temperature in an oxidizing bake-off oven where the paint residue accumulated on the filters is reduced to ash. After cooling, the ash is removed, and the filters returned to service, and the cycle is repeated. The filter comprises a frame section and a mesh media section which has a plurality of mesh portions. The mesh portions are preferably arranged in a series M.sub.1, M.sub.n-1, M.sub.n, wherein n is a positive integer of 4 or more, that are sized with the free face area A.sub.n of each mesh portion n so that the overall mesh media section has a progressive density characteristic. Thus, an excessive amount of material is not captured at the first mesh portion M.sub.1 so as to avoid "face blinding" of the filter. In paint booth operation, when the filter has completed its operating cycle, typically as determined by a air flow velocity, dirty filter elements are removed and the filter is heated remove paint residue, and producing ash. After cooling and ash removal, the filter is returned to service.

In various stages of assembly of various parts and equipment, particularly for large trucks, automobiles, construction machinery, aircraft, or the like, it is often necessary for workers to paint a large object in a containment structure commonly known as a paint booth. Although a variety of paint booth structures have been devised to effectively employ various air flow design characteristics in order to reduce paint booth operating costs while maintaining adequate paint finish quality, in the various prior art paint booth designs known to us, the paint booth operations have resulted in a large quantity of paint contaminated air filters which must be safely and legally handled and discarded. Coating overspray in a typical paint booth might be as much as fifty percent (50%) or more of the volume of coating which adheres to the object being sprayed. With increasingly stringent environmental laws, many paint contaminated filters have had to be handled as hazardous waste, and where such handling is required, a premium has been paid to dispose of such filters in hazardous waste landfills. In particular, the U.S. Environmental Protection Agency, and the environmental agencies in various U.S. states and in other nations, have promulgated regulations and strict standards which require testing and rigorous documentation for land disposal of paint loaded filters which have been produced as a result of paint booth operations.
Collection of overspray paint from a spray booth is generally achieved now by (a) use of paper type filters, (b) use of fiberglass type filters, and (c) use of a water spray curtain for knockout of paint particles to a circulating water bath. Both paper and fiberglass filters result in paint saturated filters which must pass a "paint filter test" showing the absence of free liquids, before being disposed in a landfill. Typically, such filters must be disposed, at relatively high cost, in a hazardous waste landfill. Also, wet spray booth designs result in creation of a sludge, which must be periodically removed, treated, and disposed, often by shipment to a hazardous waste landfill.
In spite of the various schemes which have so far been offered to the marketplace to reduce airflow, limit overspray, or to enhance paint filter life, a continuing and growing demand exists for a simple, inexpensive method which can be used to preserve and enhance the life cycle of paint filters, thus reducing disposal costs. The need for an improved method for paint booth operation is especially seen in conjunction with work where large mobile objects are to be painted, such as heavy haul trucks, rail cars, construction machinery, or large commercial aircraft. As will be evident to those familiar with paint booths and to whom this specification is particularly addressed, a novel filter and a method of using the filter which effectively eliminates the necessity of disposing of large quantities of spent paint filters, would be of great benefit in increasing the profitability of manufacturing plants which are now incurring large and continuing expenses with presently used filters and methods of paint booth operation.

Method of recovering paint booth filters


The present invention provides a reactive red dye composition comprising (A) 3% to 97% by weight of a reactive azo dye of the following formula (I),

1. Field of the Invention
The present invention relates to a reactive red dye composition, and particularly relates to a reactive red dye composition suitable for discharge printing.
2. Description of the Related Prior Art
Regarding the dye of fabrics, there has not been any methods existed to obtain a red dye product with good build up by a single reactive dye till this day. The only method to obtain a red dye product with good build up is by mixing different colors.
In order to obtain a reactive red dye composition with good build up, a reactive dye of the following formula (1) is generally taken as a base and then mixed with orange, yellow or other colors of reactive dyes.

The similar technology of such a color mixing dye was disclosed in several patents, such as Chinese Patents Nos. CN1524904, CN1730565, and CN1730566, PCT Patent Nos. WO2000006652 and WO2006024639, and U.S. Patent applications Nos. US2005034252 and US2005034253.

Reactive red dye composition and application thereof

Abstract: wherein W, D1 and D2 are defined the same as the specification; and (B) 97% to 3% by weight of a reactive azo dye of the following formula (II),

Abstract: wherein R, X, Z, D3 and D4 are defined the same as the specification. The reactive red dye composition of the present invention can be utilized to dye cellulose fibers. The cellulose fibers dyed by the reactive red dye composition obtain not only good build-up and level dyeing properties but also an excellent property of white discharging.


Cholesterol lowering compounds and compositions are formed from the photochemical treatment of the Zaragozic Acids followed by esterification. These compounds and compositions are active squalene synthetase inhibitors useful in the treatment of hypercholesterolemia.

Hypercholesterolemia is known to be one of the prime risk factors for ischemic cardiovascular disease, such as arteriosclerosis. Bile acid sequestrants have been used to treat this condition; they seem to be moderately effective but they must be consumed in large quantities, i.e. several grams at a time, and they are not very palatable.
MEVACOR.RTM. (lovastatin), now commercially available, is one of a group of very active antihypercholesterolemic agents that function by limiting cholesterol biosynthesis by inhibiting the enzyme, HMG-CoA reductase.
Squalene synthase (also known as squalene synthetase) is the enzyme involved in the first committed step of the de novo cholesterol biosynthetic pathway. This enzyme catalyzes the reductive dimerization of two molecules of farnesyl pyrophosphate to form squalene. The inhibition of this committed step to cholesterol should leave unhindered biosynthetic pathways to ubiquinone, dolichol and isopentenyl t-RNA.
Previous efforts at inhibiting squalene synthetase have employed pyrophosphate or pyrophosphate analog containing compounds such as those described in P. Ortiz de Montellano et al, J. Med Chem. 20, 243 (1977) and E. J. Corey and R. Volante, J. Am. Chem. Soc., 98, 1291 (1976). S. Biller (U.S. Pat. No. 4,871,721) describes isoprenoid (phosphinylmethyl) phosphonates as inhibitors of squalene synthetase.
Recently certain nonphosphorus containing inhibitors of squalene synthetase have been isolated as natural products. These natural product inhibitors are described in copending patent application Ser. No. 496,743 filed Mar. 21, 1990, Ser. No. 496,742 filed Mar. 21, 1990, now issued as U.S. Pat. No. 5,096,923, and Ser. No. 582,452 filed Sep. 13, 1990, now issued as U.S. Pat. No. 5,102,907. Semisynthetic analogs of these naturally occurring compounds have been reported in copending application Ser. No. 698,766 filed May 10, 1991. A need still remains for a more effective squalene synthetase inhibitor, i.e., one that provides a greater antihypercholesterolemic effect and exhibits a good safety profile.
The natural product inhibitors are tricarboxylic acids. The present applicants have now found that these natural products known as zaragozic acid A, zaragozic acid B and zaragozic acid C undergo a photochemical reaction yielding monocarboxylic derivatives of the zaragozic acids, which are potent cholesterol lowering agents. The present invention discloses esters of these monocarboxylic acids.


The present invention relates generally to cinnamate crosslinkers. Specifically, the present invention relates to gels, biochips, and functionalized surfaces useful as probes, in assays, in gels, and for drug delivery, and methods of making the same using a newly-discovered crosslinking configuration.

Complex self-assembly processes require components to associate with particular partners in a preprogrammed fashion. DNA functionalization of nanoconstructs, nanoparticles, and micron-scale colloids has proven effective in getting specific cohesion between pairs of components and in forming structures. The hybridization behavior of DNA has been extensively studied for decades. Aside from genetic detection, DNA hybridization has been used to build designable DNA nano-structures, DNA-directed nano-particle structures, and micron particle structures. Such DNA engineering techniques can be utilized for DNA computing (processors), and in DNA chips, multifunctional colloidal particles as used in drug delivery, and complex colloidal self-assembly.
The highly specific, thermoreversible paired interactions that are formed by complementary DNA strands play an important role in biology and have recently been exploited as key building blocks particularly in nanotechnology as a strategy to selectively bind and create a host of potentially important structures and functional systems including crystals, motors/robots, computers, replicators, and machines. It is highly desirable to crosslink some or all of these bonds permanently for nanotechnological applications, as well as for biological assays. Several crosslinking methods have been investigated previously. Psoralen, a highly exploited crosslinking agent, intercalates between hybridized thymidine-adenosine dinucleosides in a DNA sequence and reacts with the thymines upon exposure to UV light, forming covalent links. However, the crosslinking efficiency for psoralen in solution is low (effective cross section 5×10−6 nm2) or requires a very specific attachment of the psoralen group at the start of a DNA "sticky end" next to a T-A sequence.
Cinnamate is one of the most extensively studied photo-crosslinkers used in DNA hybridization. Cinnamate-functionalized polymers are known to undergo crosslinking via photocycloaddition reactions upon exposure to UV radiation. Generally, cinnamate attaches to DNA strands using a phosphoramidite group, wherein a cinnamate on one strand is photo-crosslinked with an adjunct adenine base on another strand. However, the crosslinking efficiency is low, requiring approximately 30 minutes of incubation time for hybridization given an intensity of about 5.7 mW/cm2.
There remains, therefore, a need for efficient, specific, and permanent DNA crosslinking methods for use in biological assays, drug delivery, processors, and other nanoparticle structures.

DNA photolithography with cinnamate crosslinkers


Tire tread comprising a tread surface intended to come into contact with a roadway, this tread comprising at least one sipe extending in a main direction D and of mean width E, this sipe comprising in the main direction D at least one part sipe of shallow depth HF and at least one part sipe of great depth HG, the depth HF being less than the depth HG, each part sipe of shallow depth and each part sipe of great depth comprising an end region, this tread further comprising at least one insert oriented in a direction different from the main direction D of the sipe, this insert being positioned wholly within the thickness of the tread so as to be situated radially on the inside of a part sipe of shallow depth HF, this tread being such that at least the part sipe of shallow depth HF situated radially on the outside of the insert is provided, at its end region, with a widening forming a channel of maximum width W, this maximum width W being greater than the mean width E of the sipe.

1. Field
The present invention relates to tire treads and notably to the sipes with which these treads may be provided. It also relates to the treads comprising inserts intended to form new grooves after these treads have become partially worn, these treads also comprising sipes according to the invention.
2. Description of Related Art
It is known practice to form a tread having a tread surface that is intended to come into contact with a roadway, this tread having sufficient thickness to allow a satisfactory service distance to be covered through wear. It is known practice to provide the tread of a tire intended to be fitted to a passenger vehicle with a plurality of grooves the depth of which is suited to the grooves being present and effective throughout the service life. In combination with these grooves there are a plurality of sipes which make it possible to generate a great many edge corners of material without, however, excessively reducing the stiffness of the tread and without excessively increasing the voids volume of this tread.
In order to obtain in the initial state (which means as it leaves the mold) a suitable level of stiffness while at the same time ensuring a high number of voids at the end of life so that the tire has a great deal of wet grip, it has been proposed that new grooves be generated once tire wear reaches a certain level by either forming channels inside the tread or by introducing into the tread at least one insert which, when removed, forms a new grooves as described for example in patent document BE-399026-A.
In the latter instance, it is advantageous to combine both the presence of at least one insert and a plurality of sipes the orientation of which intersects the orientation of the insert.
During testing it has been found that movements of unvulcanized material can occur during the tire molding operation; these movements of material are not without impact on the geometry of the constituent parts and, more particularly of the inserts themselves that is obtained, and this can lead to a reduction in the running performance of the tire. In particular, it has been found that, with wear of the tread, the switchover from the sipe to the new groove formed by the insert is sometimes nonuniform and that can present problems.
It is an object of the invention to prevent such a problem.

COMPAGNIE GENERALE DES ESTABLISSEMENTS MICHELIN


Down-the-hole drilling machine comprising a housing in form of a tube (1), a hammer piston (6) being movable to-and-fro in the tube and intended for impacting a drill bit (5). The hammer piston is at its ends provided with end sections in form of polygons with rounded corners (51, 52). These end sections are turned relative to each other an angle which is half as large as the angle between two adjacent corners.

The present invention relates to a down-the-hole drilling machine. More particularly the invention relates to the guiding of the hammer piston in a down-the-hole drilling machine.
In prior art down-the-hole drilling machines a common reason for breakdown has been that the hammer piston has seized upon bending of the surrounding tube. Such bending is caused because the drill hole becomes bent because of inhomogeneities in the ground. One effort to solve this problem has been to make the hammer piston with short guides. However, this has meant that the guides have been worn down quickly with increased air consumption and had functioning as a consequence.


A multi-engine aircraft having one engine positioned at the tail of the fuselage may include rear tail units in a vertical longitudinal plane-of-symmetry of the fuselage. The tail engine is disposed in front of the rear tail units on the upper part of the tail of the fuselage. The tail engine is mounted, in a detachable manner, on a rigid supporting structure attached to the supporting structure of the fuselage. A lowering shaft, formed in the tail of the fuselage and plumb with the engine, is supported by the rigid supporting structure. The lowering shaft provides a passage for the engine between a high position corresponding to the operational position of the engine and a low position in which the engine is removed from the fuselage.

Such is the case in particular with tri-jet aircraft such as the Lockheed L1011, and the McDonnell Douglas DC-10, or MD-11., In fact, whilst two of the engines are respectively carried by the wings, the third engine is structurally and geometrically located between the horizontal tail unit with its two symmetrical stabilizers and the vertical tail unit with its vertical stabilizer disposed on the nacelle or the fairing of this third engine. Other aircraft integrate the tail engine at the end of the fuselage, directly in its structure.
Whatever the type of aircraft equipped with such an engine at the tail of the fuselage may be, particular maintenance problems arise due to the location of said engine compared with that of a very accessible and easily removable wing engine. In fact, when it is desired to remove the engine for an important overhaul, or even to replace it, it is necessary to previously carry out the removal of numerous surrounding components and devices that are independent of the engine in order to gain access to the latter, which results in particularly long, tedious and costly interventions.
Furthermore, it is necessary to provide complex and heavy lifting and/or handling installations (considering the height of the intervention) in order to be able to carry out in complete safety the various movements (horizontal and vertical) for taking out and moving the engine from the rear tail units or the fuselage to a receiving stand placed on the ground.

Multi-engined aircraft with lowering shaft


A coolant subsystem for a torpedo propulsion system having an external costion expansion engine. The coolant subsystem includes a valve which provides for one-way flow through the coolant subsystem. Inclusion of the valve prevents a backflow of exhaust gas into the coolant subsystem, thereby reducing the risk of torpedo failure due to engine overheating when the torpedo is launched in shallow water.

(1) Field of the Invention
This invention relates generally to torpedoes, and more particularly relates to a coolant subsystem for cooling the combustion chamber and/or cylinders of a torpedo propulsion system.
(2) Description of the Prior Art
Conventional torpedo engines employ coolant subsystems which rely upon seawater as a cooling medium. Generally, such coolant subsystems include a water inlet for receiving seawater, which is then pumped through the engine and emitted from the torpedo with the exhaust gas. While this type of coolant subsystem is reliable when a torpedo is launched from a substantial depth, torpedoes launched in shallow water will, on occasion, shut down and not complete their mission requirements. While numerous attempts have been made to determine the cause of such failures and to eliminate them, prior attempts have been only marginally successful in reducing the rate of engine failure, primarily because they have been unsuccessful in determining the actual cause of engine shutdown. Failure rates were reduced somewhat by implementation of engine start-up software changes, however a 3-5% failure rate has continued.

Coolant subsystem for a torpedo propulsion system

The United States of America as represented by the Secretary of the Navy


A system and method for verifying user identity, in accordance with the present invention, includes a conversational system for receiving inputs from a user and transforming the inputs into formal commands. A behavior verifier is coupled to the conversational system for extracting features from the inputs. The features include behavior patterns of the user. The behavior verifier is adapted to compare the input behavior to a behavior model to determine if the user is authorized to interact with the system.

1. Field of the Invention
The present invention relates to natural language understanding systems, and more particularly to a method and system for non-intrusively verifying a user based on behavior of the user.
2. Description of the Related Art
Traditional methods for speaker verification (or identification) rely on specific inputs from the user for the sole purpose of the verification. These methods may include providing speech samples and answering biometric questions. Once verified, the speaker is permitted to access the target system, and typically no further verification is performed. Even if additional verification is performed, it requires more specific inputs from the user for the purpose of verification. This is intrusive to the user.
Prior art speaker verification systems (or user verification systems, for systems without a spoken input modality) validate the identity of a given user on the basis of one or more of the following criteria:                1. Who the user is, which may be determined by the user's voice, fingerprint, handwriting, etc.        2. What the user knows, which may be determined by a password, or answers to some biometric questions (e.g., what is the mother's maiden name?), etc.        3. What the user possesses, such as an identification document, a key, a cellular phone with a particular number, etc.
All of the above methods for verification may be defeated if an imposter knows or possesses the information, such as the key or a maiden name, etc.
Therefore, a need exists for a method and system for determining an identity of a user based on the users behavior. A further need exists for a non-intrusive user verification system.

Method and system for non-intrusive speaker verification using behavior models


A method of making a plurality of light emitting diodes simultaneously includes steps of: a) providing a wafer and a first bonding layer, and adhering the first bonding layer to a bottom side of the wafer; b) cutting the wafer to form a plurality of LED dies on the first bonding layer; c) adhering a second bonding layer on top sides of the plurality of LED dies; d) removing the first bonding layer; e) mounting the second bonding layer with the plurality of LED dies on a base having a plurality of recesses; f) removing the second bonding layer and letting the plurality of LED dies fall into the recesses of the base; g) electrically connecting the LED dies to electric poles in the base; h) encapsulating the LED dies; and i) cutting the base to form the plurality of LEDs.

1. Technical Field
The disclosure generally relates to a method of making light emitting diodes, and particularly to a method of making a plurality of light emitting diodes simultaneously.
2. Description of Related Art
In recent years, light emitting diodes (LEDs) have been widely used in illumination. Typically, an LED device includes a plurality of LEDs. Each LED includes an LED chip arranged in a reflector cup and electrically connected to an external circuit. In addition, the LED chip is packaged to protect it from environmental harm and mechanical damage. However, generally, to form the plurality of LEDs, each LED chip is individually mounted into the reflector cup and then connected to a circuit board through wire bonding, and finally transparent material is filled into the reflector cup to encapsulate the LED chip to form an LED. In other words, the LEDs are formed separately at a time, which is costly, time-consuming and may require substantial amounts of manual labor and/or specialized equipment.
For the foregoing reasons, therefore, there is a need in the art for a method for making LEDs which overcomes the limitations described.


A method and system for storing at least one miniature is disclosed. Each of the at least one miniature includes a base and a model. The base has a shape. The method and system include providing a tray and a tray container. The tray has a slot therein. The slot is for holding the base of each of the at least one miniature. In one aspect, the slot is configured such that a portion of the slot conforms to the shape of the base. In another aspect, the slot has a stationary portion and a movable portion. The stationary and movable portions of the slot are to allow the at least one miniature to be placed within the slot and to allow a portion of the slot to conform to the shape of the base. The tray container is for storing the tray.

The present invention relates to miniatures, and more particularly to a method and system for storing miniatures in a secure manner.
Individuals throughout the world collect miniatures, such as wargaming or collectible miniatures. FIGS. 1A and 1B generally depict miniatures 10 and 20. Each miniature 10 and 20 typically includes a base 12 and 22, respectively, and a model 14 and 24, respectively. The bases 12 and 22 are typically rectangular (e.g. square), as is the base 12, or circular, as is the base 22. In addition, the bases 12 and 22 are typically standard sized. For example, the circular base 22 is typically twenty-five millimeters in diameter at the bottom. The square base 12 is typically twenty millimeters by twenty millimeters, twenty-five millimeters by twenty-five millimeters or forty millimeters by forty millimeters at the bottom. Both the rectangular base 12 and the circular base 22 have sloped, or beveled, edges. The edges of the base 12 and the base 22 are sloped at approximately the same angle. In contrast, the size of the models 14 and 24 vary greatly in both size and shape. For example, the models 14 and 24 typically range between one-half and three inches in height. In addition, the models 14 and 24 are typically relatively fragile. Thus, it is easy to break a portion of the miniature 10 and 20.
Because individuals often collect a large number of miniatures 10 and 20, some mechanism for storing and transporting the miniatures 10 and 20 is desired. The mechanism should hold the miniatures 10 and 20 securely to prevent damage. However, it is desirable for the mechanism not to contact the models 14 and 24 to prevent wear and tear on the models 14 and 24, respectively.
FIG. 2 depicts a conventional case 30 for storing miniatures. The conventional case 30 typically has a plastic shell (not shown). Within the shell, a conventional foam separator 32 and a conventional foam insert 34 are used to store miniatures. The conventional foam separator 32 is used to separate layers of the conventional foam insert 34, allowing many miniatures 10 and 20 to be stored. The conventional foam separator 32 is typically approximately one half inch in thickness. Several apertures 34 (only one of which is labeled) are typically cut in the conventional foam insert 34. The conventional foam insert 34 is typically one inch thick. Each aperture 36 is typically one inch by one and one half inch. Each aperture 36 is for holding a single miniature 10 or 20. Thus, an individual would insert miniatures 10 and 20 into the apertures 36 of a conventional foam insert 34, separate different foam inserts using the conventional foam separator 32, and stack these layers within the plastic shell (not shown).
Although the conventional case 30 functions for some miniatures 10 and 20, one of ordinary skill in the art will readily recognize that it has several drawbacks. Most notably, the conventional case does not provide adequate protection for many miniatures 10 and 20. Miniatures which have bases that are larger than the apertures 36 require that the apertures 36 be modified. For miniatures 10 having a base that is forty millimeters by forty millimeters, the apertures 36 often must extend through several layers of foam inserts 34. On the other hand, miniatures 10 and 20 which are too small for the apertures 36 are often jostled during transportation in the conventional case 30. These miniatures 10 and 20 may suffer damage during transportation in the conventional case 30.
FIG. 3 depicts a portion of another conventional case 50. The case 50 typically has a hinged outer shell (not shown) that is in function to a suitcase. Within the outer shell are conventional foam inserts 52 and 54. Each conventional foam insert 52 and 54 has a conventional dimpled pattern 56 and 58, respectively. The dimpled patterns 56 and 58 have a shape that is sometimes known as an xe2x80x9cegg-cratexe2x80x9d or xe2x80x9cegg-cartonxe2x80x9d pattern. The conventional dimpled patterns 56 and 58 are formed to interlock. In other words, where one conventional dimpled pattern 56 or 58 is concave, the other conventional dimpled pattern 58 or 56, respectively, is convex. The conventional foam inserts 52 and 54 are also very soft. In order to use the conventional case 50, miniatures 10 and 20 are placed in the depressions of one of the conventional dimpled patterns 56 or 58. When the conventional case 50 is closed, the interlocking nature of the conventional dimpled patterns 56 and 58 helps to hold the miniature 10 or 20 in the depression in which the miniature 10 or 20 was placed.
Although the conventional case 50 functions, miniatures 10 and 20 may be damaged when carried in the conventional case 50. The interlocking conventional dimpled patterns 56 and 58 often allow the miniatures 10 and 20 stored therein to move to a certain extent. Thus, the miniatures 10 and 20 might be damaged. In addition, the models 14 and 24 often have small features that poke into the conventional foam inserts 52 and 54. Thus, when the conventional case 50 is opened, the miniature 10 or 20 may stick to the top of the case. Furthermore, the miniatures 10 and 20 stored in the conventional case 50 must be spaced apart to prevent them from contacting each other and causing damage. Thus, the conventional case 50 cannot hold a high density of miniatures.
Accordingly, what is needed is an improved system and method for storing miniatures. The present invention addresses such a need.
The present invention provides a method and system for storing at least one miniature. Each of the at least one miniature includes a base and a model. The base has a shape. The method and system comprise providing a tray and a tray container. The tray has a slot therein. The slot is configured to hold the base of the at least one miniature. In one aspect, the slot is configured such that a portion of the slot conforms to the shape of the base. In another aspect, the slot has a stationary portion and a movable portion. The stationary and movable portions of the slot are to allow the at least one miniature to be placed within the slot and to allow a portion of the slot to conform to the shape of the base. The tray container is for storing the tray.
According to the system and-method disclosed herein, the present invention provides a storage system for miniatures which can securely hold individual miniatures with little or no damage.

Method and system for storing miniatures


A method of treating systemic afflictions includes loading a dental floss with an active therapeutic agents and rubbing the floss against a mouth tissue to release the active therapeutic agent onto the tissue for penetration through the tissue. The active therapeutic agent is selected from the group consisting of zinc sulfate, zinc chloride, zinc acetate, zinc phenol sulfonate, zinc borate, zinc bromide, zinc nitrate, zinc glycerophosphate, zinc benzoate, zinc carbonate, zinc citrate, zinc hexafluorosilicate, zinc diacetate trihydrate, zinc oxide, zinc peroxide, zinc salicylate, zinc silicate, zinc stannate, zinc tannate, zinc titanate, zinc tetrafluoroborate, zinc gluconate, and zinc glycinate. An additional therapeutic agent may also be loaded on the floss, for example, antimicrobials, antibiotics, antioxidants, anti-plaque agents, analgesics, anti-tarter agents, anti-caries agents, hemostatic agents, anti-inflammatory agents, hormones, bleaching agents and vitamins.

Before the onset of disease, healthy pink gingiva (gum tissue) surrounds the teeth, both holding them in place and preventing infectious material from entering the jaw bone or tooth itself. The tooth includes three regions known as the crown, neck, and root. Gingiva or gum tissue is the soft tissue covering the neck of the tooth. The area between the enamel and the gingiva is called the gingival crevice. The gums are under constant bacterial assault. Gingivitis develops when large masses of bacteria clog the gingival crevice.
Periodontal disease (gum disease) is one of the most prevalent chronic diseases affecting humans. Children as young as 5 years of age can have gum disease. By age 35, three out of four people are afflicted, and by age 65, an estimated 98 percent of Americans have periodontal disease." The word "periodontal" is derived from two Greek words that mean "around the tooth periodontal disease is caused by certain types of bacteria, forming a sticky, colorless, constantly forming film of bacteria called plaque. Plaque that is not removed can combine with other materials and harden into a rough, porous deposit called calculus (tartar). Calculus on the tooth surface (above the gum line) may not contribute to periodontal disease, but calculus on the neck or root surface (below the gums) makes removal of new plaque and bacteria more difficult. Bacteria in plaque produce metabolic by-products that diffuse into the immediate surrounding area, irritate the gingiva, and result in an inflammatory reaction. The gingiva then swells, becomes reddened, sensitive to touch and may bleed. It is not normal for gums to bleed when brushing or flossing. Bleeding gums is usually the first sign of gingivitis. Gingivitis is reversible. Gum disease occurs when the gingival crevice between the tooth and gum is more than three millimeters. As gingivitis progresses, the tissue surrounding the teeth is destroyed, the supporting collagen fibers begin to degenerate, and eventually the bone supporting the tooth socket degenerates and tooth loss can occur.
Periodontal disease can be prevented by practicing good oral hygiene. Daily tooth brushing and flossing are the most important weapons against the formation of plaque. Brushing teeth thoroughly at least twice a day helps remove plaque from the outer, inner, and chewing surfaces of the teeth. But careful brushing alone is not sufficient, because the bristles of the toothbrush cannot make contact with all parts or sides of the teeth. Dental floss helps to remove plaque from the crevices between the teeth that are often too deep to access with a brush.
Dental floss or tape is typically a multi-filament bundle of natural or synthetic fibers of varying thickness, usually in a continuous strand, sometimes coated with wax or other polymers and housed on a spool for ease of dispensing. Using dental floss to help remove plaque from the tooth surface is known in the art. It has been known in the art to coat or otherwise fix substances to dental floss for application of those substances to the teeth and gums to achieve therapeutic effects to the teeth and gums. Certain of these known are herein described:

Therapeutic dental floss for treating systemic diseases


A wiring board includes: a flexible insulating base 1; a plurality of conductive wirings 2 arranged on the flexible insulating base 1; protruding electrodes 3 provided respectively at an end portion of the same side of each of the conductive wirings; external terminals 4, 5 formed respectively at the other end portions of each of the conductive wirings; metal plating layers applied on the conductive wirings, the protruding electrodes and the external terminals; and solder resist layers 7 formed respectively by coating the conductive wirings in regions between the end portions at which the protruding electrodes are provided and the external terminals. In the regions where the solder resist layers are formed, no metal plating layers are formed on the conductive wirings, and the surfaces of the conductive wirings to be contacted with the flexible insulating base are rougher than the surfaces not to be contacted with the flexible insulating base. Even when a film base is thin, bending stress applied to the conductive wirings is relieved sufficiently, and thus breaks in the wirings are suppressed.

1. Field of the Invention
The present invention relates to a wiring board such as a tape carrier substrate formed by providing a conductive wiring on a flexible insulating base. Particularly, the present invention relates to a structure of a wiring board having conductive wirings whose folding resistance is improved.
2. Description of Related Art
As one type of package module using a tape carrier substrate, the one employing a COF (Chip On Film) has been known. The COF includes a semiconductor chip mounted on a flexible insulating tape carrier substrate and the mounted portion is protected by sealing with a resin. The tape carrier substrate includes as main components an insulating film base and a plurality of conductive wirings formed on a surface of the film base. In general, polyimide is used as a material of the film base and copper is used as a material of the conductive wirings. As required, a metal plating film and a solder resist layer as an insulating resin are formed on the conductive wirings.
The COF is used mainly for packaging a driver for driving a display panel such as a liquid crystal panel. In such a case, conductive wirings on the tape carrier substrate are arranged in two groups of a first group for forming external terminals for output signals and a second group for forming external terminals for input signals, and a semiconductor chip is packaged between the first group of conductive wirings and the second group of conductive wirings. The first group of conductive wirings forming the external terminals for output signals are connected to electrodes formed in the periphery of the display panel, and the second group of conductive wirings forming the external terminals for input signals are connected to terminals of a mother board.
On the other hand, a packaging method of folding the tape carrier substrate at its end portion is used for providing a smaller structure to be packaged in the display panel. For facilitating folding at an acute angle, it is known to previously form a slit at the portion of the film base to be folded so as to fold only a copper foil lead that forms the conductive wirings.
However, in the structure, since the film base is not provided at the folded portion where the slit is formed, mechanical stress during the packaging or stress caused by a heat cycle or the like will be concentrated to the conductive wirings made of a thin copper lead, and cracks and ruptures in the conductive wirings can occur easily. Particularly, in a case of Sn plating or Sn-Pb plating both of which are provided most widely on conductive wiring, a brittle Cu-Sn diffused alloy layer is formed on the interface between the copper foil lead and the plating due to the heat applied during the package assembly process, and thus the folding resistance of the conductive wirings is degraded considerably.
A structure for improving the folding resistance of the conductive wirings is described in JP H05-326643 A, for example. In this structure, either Sn or Sn alloy is not plated on the surface of the copper foil lead positioned on a folding slit formed on a film base, and furthermore, a flexible resin film (solder resist) having a plating resistance and insulation is provided on the surface of a copper lead positioned on the folding slit.
However, even in the wiring board having the above-mentioned conventional structure, folding resistance of the conductive wirings made of a copper lead cannot be sufficient anymore. The reason is that, in accordance with the trend for smaller packages using tape carrier substrates, thicknesses for all the components have been reduced. For example, the thickness of the film base of polyimide is about 40 μm, the thickness of the conductive wirings is about 8 μm, and the thickness of the solder resist is about 15 μm. As a result, even at the time of folding the conductive wirings with the film base, stress being not much different from the case of folding the conductive wirings alone will be applied, so that the conductive wirings can be broken easily. In light of this, there is a demand for a structure for relieving sufficiently the bending stress applied to the conductive wirings.

Wiring board, semiconductor device and display module

Matsushita Electric Industrial Co., Ltd.


The present invention provides antibodies that bind to human interleukin-25 (IL-25) and methods of using the same. According to certain embodiments, the antibodies of the invention bind human IL-25 with high affinity. In certain embodiments, the invention includes antibodies that bind human IL-25 and block IL-25-mediated cell signaling. The antibodies of the invention may be fully human, non-naturally occurring antibodies. The antibodies of the invention are useful for the treatment of various disorders associated with IL-25 activity or expression, including asthma, allergy, chronic obstructive pulmonary disease (COPD), inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease, atopic dermatitis (AD), and Eosinophilic Granulomatosis with Polyangiitis (EGPA), also know as Churg-Strauss Syndrome.

Interleukin-25 (IL-25) is a cytokine that is structurally related to interleukin-17 (IL-17) and is sometimes referred to as IL-17E. It is a secreted, homodimeric glycoprotein that interacts with and signals through the heterodimeric IL-17RB/IL-17RA receptor (Iwakura, et. al., (2010), Immunity, 34:149). IL-25 is produced by Th2 cells, epithelial cells, endothelial cells, alveolar macrophages, mast cells, eosinophils and basophils (Rouvier, E. et. al., (1993), J. Immunol. 150:5445-5456; Pan, G. et. al., (2001), J. Immunol. 167:6559-6567; Kim, M. et. al., (2002), Blood 100:2330-2340). Signaling through IL-25 is associated with eosinophil recruitment, initiation of Th2 and Th9 responses and suppression of Th1 and Th17 cell responses. IL-25 induces the production of other cytokines, including IL-4, IL-5 and IL-13, in multiple tissues (Fort, M M et. al., (2001), Immunity 15:985-995).
IL-25 has been implicated in chronic inflammation associated with the gastrointestinal tract and the IL-25 gene has been identified in a chromosomal region associated with autoimmune diseases of the gut, such as inflammatory bowel disease (IBD) (Buning, C. et. al., (2003), Eur. J. Immunogenet. October; 30(5): 329-333). IL-25 has also been shown to be upregulated in samples from patients with asthma (Sherkat, R. et. al., (2014), Asia Pac. Allergy October; 4(4):212-221). Accordingly, blockade of IL-25 signaling may be useful for the treatment of various disorders associated with IL-25 activity or expression.
Anti-IL-25 antibodies are mentioned, e.g., in U.S. Pat. Nos. 8,785,605; 8,658,169 and 8,206,717; and PCT publications WO2011/123507; WO2010/038155 and WO2008/129263. Nonetheless, there is a need in the art for novel IL-25 antagonists, such as the anti-IL-25 antibodies of the present invention, for the treatment of diseases or disorders associated with IL-25 expression and/or signaling, or other conditions associated with IL-25 expression and/or signaling.


A system for disabling a device. An embedded identifier contained within a cable security system is read in response to enabling a cable security mechanism within the device. The device is disabled if the embedded identifier is not found.

1. Field of the Invention
The present invention relates generally to an improved electronic device security system. More specifically, the present invention is directed to a method, system, and computer usable program code to disable an electronic device upon theft.
2. Description of the Related Art
Currently, there is an ever increasing need to provide security for electronic devices against the unauthorized removal or theft of these electronic devices. The high cost and portability of such electronic devices results in the higher risk of theft. Electronic devices, such as, for example, laptop computers, stereos, and televisions, are a frequent target for theft from homes, offices, stores, college dorm rooms, and libraries. Some electronic devices, such as projectors, are even more at risk of theft because projectors are frequently left unattended in conference rooms.
In addition, security is required to prevent the theft of data contained on electronic devices, such as personal and laptop computers. Theft of the computer itself sometimes is not as great a loss as the data contained therein. The data may be of such significance as to warrant extreme measures in protecting it. As a result, deterrence of and protection from theft of computer data is of paramount importance to all who use computer systems as well.
Accordingly, a number of methods have been developed for guarding against the unauthorized removal of electronic equipment and the data contained therein. One such method of protection is anchoring the electronic device to a desktop, or other immovable object, with a locking cable mechanism. While this method provides a physical deterrent to theft, the cable can be cut and the electronic device removed with the cable system lock still attached to the electronic device. Since the electronic device can still operate, the electronic device is still of value to the thief.
Another method is the use of a key lock switch on the front panel of a computer itself to protect the data contained therein. However, a determined thief can bypass the computer disable key lock switch. Encoding data may be another method of safeguarding computer records but requires extra enciphering and deciphering programs which increase access decoding and storage encoding time when a user wants to work with the data.
Another method of protection includes the attachment of non-removable tags to the electronic devices. This method requires the use of sensing devices that are responsive to the non-removable tags. These tag sensing devices are located at exits from the premises where the electronic devices are located. However, these tag sensing devices are rather expensive. Consequently, this method is generally not very feasible, especially when multiple exit points exist.
Another method of theft protection includes sensing a current loop coupled to the protected electrical device. This method includes a plurality of electronic tethers which are connected to individual pieces of protected equipment by way of connectors which in turn are bonded to the surface of the protected equipment. Each tether includes a pair of conductors which are connected together to form a closed current loop via a series of resistor and conductive foil, which is adhesively bonded to the outside of the equipment. However, it is conceivable that a thief may carefully remove the current loop without detection.
Therefore, it would be beneficial to have a method, system, and computer useable program code for disabling electrical devices upon theft and ensuring that the data contained within the stolen electronic devices cannot be retrieved by unauthorized persons.

Method and system for disabling an electronic device upon theft

International Business Machines Corporation