The present invention relates to infectious bovine rhinotracheitis viruses which fail to produce any functional thymidine kinase as a result of an insertion in the thymidine kinase gene, vaccines against infectious bovine rhinotracheitis containing the same and methods for production and use of same. The present invention also relates to infectious bovine rhinotracheitis-based viral vectors useful for the coexpression of foreign genes.

I. Infectious Bovine Rhinotracheitis Disease
The alpha herpesvirus, bovine herpesvirus type 1 (hereinafter "BHV-1"), more commonly known as infectious bovine rhinotracheitis virus (hereinafter "IBRV") and infectious pustular vulvovaginitis virus (hereinafter "IPV"), is a direct cause of bovine disease and is a major factor in the initiation of bacterial pneumonia (Ludwig, H., In: The Herpesviruses., Ed. B. Roizman, 2:135-314 (Plenum Press: New York) (1983); Pastoret, P. P., et al, Ann. Rech. Vet., 13:221-235 (1982); Yates, W. D. G., Can. J. Comp. Med., 46:225-263 (1982); Gibbs, E. P. J. et al, Vet. Bull. (London) Part I, 47:317-343 (1977); and Gibbs, E. P. J. et al Vet. Bull. (London) Part II, 47:411-425 (1977)). Infectious bovine rhinotracheitis (hereinafter "IBR") has a worldwide distribution and is probably the single most costly disease of cattle in the United States. Respiratory IBR disease in the United States costs about $25 million. Additional losses associated with IBRV infections result from abortion storms, fatalities in newborn calves, losses in milk yield, conjunctivitis, metritis, enteritis and meningitis.
The spread of IBR in naturally and artificially bred cattle poses a serious problem, especially with the continued widespread use of frozen semen. Recurrent shedding of virus from infected bulls also constitutes a significant threat to the artificial insemination industry in the United States and to the worldwide distribution of bovine germ plasm. The incrimination of IBRV as the etiologic agent of oophoritis and salpingitis with resultant infertility and sterility adds to the seriousness of IBRV infections.
The severity of illness resulting from IBRV infections depends on the virus strain and on the age of the animal affected. After recovery from infection, animals may show signs of recurrent disease without being reexposed to the virus. Recurrent disease without reexposure occurs because the virus remains dormant, i.e., latent, in neurons of the sensory ganglia of its host and can be reactivated, even after long periods (Rock, D.L. et al, J. Gen. Virol., 67:2515-2520 (1986); Homan, E. J. et al, Am. J. Vet. Res., 41:1212-1213 (1980); and Rodriguez, L. L. et al, Am. J. Vet. Res., 45:1069-1072 (1984)). Dexamethasone treatment can also provoke recrudescence of virus shedding with or without clinical symptoms of active IBR. This suggests that reactivation and release from neuronal sites and, possibly, persistent infection of other tissues, can occur (Narita, M. et al, Am. J. Vet. Res., 42:1192-1193 (1981); Sheffy, B. E. et al, J. Am. Vet. Med. Assoc., 163:850-851 (1973); Homan, E. J. et al, Am. J. Vet. Res., 43:309-313 (1983); Ackermann, M. et al, Am. J. Vet. Res., 43:36-40 (1982); Ackermann, M. et al, Veter. Microbiol, 9:53-63 (1984); and Edwards, S. et al, Veter. Microbiol, 8:563-569 (1983)). However, reactivation of IBRV from latency can also occur spontaneously, so that cattle latently infected with field strains of IBRV represent a sporadic source of virus transmission and herd infection.
II. Known IBR Vaccines
Control of IBR is based largely on vaccination. However, vaccination may not prevent second infections by pathogenic field strains, although vaccination does increase the effective dose required to initiate second infections and it reduces the amount and duration of virus shedding. Further, vaccinated animals have less severe clinical signs than unvaccinated animals. As a result of all these factors, spread of pathogenic field strains in the herd may be reduced by vaccination.
Currently, three types of IBR vaccines are being employed: (1) killed virus vaccines; (2) subunit vaccines; and (3) modified-live virus (hereinafter "MLV") vaccines (U.S. Pat. Nos. 3,634,587 3,925,544 and 4,291,019). Killed IBR vaccines have been produced by treating IBRV with chemicals, such as formalin or ethanol, and/or physical agents, such as heat or ultraviolet irradiation. Subunit IBR vaccines have been prepared by solubilizing IBRV-infected cell cultures with nonionic detergents and purifying some of the solubilized virus proteins (Babiuk, L. A. et al, Virol., 159:57-66 (1987)). Early MLV vaccines were designed for parenteral administration and consisted of IBRV attenuated by rapid passage in bovine cell cultures or by adaptation of IBRV to porcine or canine cell cultures, by adaptation to growth in cell culture at a low temperature (30.degree. C.), or by selection of heat-stable virus particles (56.degree. C. for 40 min). Specialized types of MLV vaccines are those administered intranasally. These MLV vaccines have been attenuated by serial passage in rabbit cell cultures or by treatment of IBRV with nitrous acid followed by selection for temperature-sensitive mutants (Todd, J. D. et al, J. Am. Vet. Med. Assoc., 159:1370-1374 (1971); Todd, J. D. et al, Infect. Immun., 5:699-706 (1973); Zygraith, N. et al, Res. Vet. Sci., 16:328-335 (1974); Kucera, C. J. et al, Am. J. Vet. Res., 39:607-610 (1978); and Smith, M. W. et al, Can. Vet. J., 19:63-71 (1978)). Temperature-sensitive virus vaccines are restricted in their replication to the nasal mucosa because the temperature of the nasal mucosa is several degrees lower than that of the body. Temperature-sensitive viruses are unable to replicate at the higher temperatures of the lower respiratory tract. Hence, their growth and spread in the body is self-limiting.
The currently available IBR vaccines discussed above have serious disadvantages and have, therefore, proved unsatisfactory in commercial use. More specifically, although killed IBRV vaccines are considered to be safer than MLV vaccines, i.e., they cannot establish latency and they eliminate the problem of postvaccination shedding, they are expensive to produce, must be administered several times, and disadvantageously require adjuvants. In addition, with their use, there is the possibility of fatal hypersensitivity reactions and nonfatal urticaria. Further, some infectious virus particles may survive the killing process and thus cause disease. Moreover, animals vaccinated with killed IBRV vaccines can be infected at a later time with virulent virus. The virulent virus can establish a latent infection and can be reactivated and shed, thereby spreading infection in the herd (Frerichs, G. N. et al, Vet. Rec., 111:116-122 (1982); Wiseman, A. et al, Vet. Rec., 104:535-536 (1979); and Zuffa, A. et al, Zentralbl. Veterinaermed. Reihe B., 27:725-733 (1980)). Accordingly, although killed IBR vaccines can provide some protection against IBR, they are generally inferior to MLV vaccines in providing long term protection.
Subunit vaccines are often less toxic than killed virus vaccines, and may induce novel immunologic effects which can be of significant value. The technique for subunit vaccine preparation involves removal of capsid proteins, while leaving intact antigenic proteins that elicit protective immunity. This creates a potential for the development of serologic procedures to differentiate vaccinated from naturally infected animals. Further, subunit vaccines, though antigenic, do not contain live virus and, thus, cannot be transmitted to other animals, cause abortion, or establish latency (Lupton, H. W. et al, Am. J. Vet. Res., 41:383-390 (1980); and le Q. Darcel, C. et al, Can. J. Comp. Med., 45:87-91 (1981)). However, subunit vaccines, like killed vaccines, do not generally prevent infection and latency when animals are subsequently exposed to virulent IBRV field strains. Other disadvantages of subunit vaccines are the high cost of purification and the requirement of several injections with adjuvant.
MLV IBR vaccines have the important advantage that they produce rapid protection and activate cell-mediated and humoral components of the immune system. In the case of intranasal (hereinafter "IN") administration, localized immune responses that suppress later replication of virulent IBRV in the respiratory tract contribute significantly to protection. The local immune responses include production of interferon and IgA antibodies in nasal secretions (Kucera, C. J. et al, Am. J. Vet. Res., 39:607-610 (1978)). Extensive utilization of MLV IBR vaccines has reduced the frequency of occurrence of IBR. However, most of the available MLV IBR vaccines are not entirely satisfactory. More specifically, there is concern as to their safety, especially if the vaccine virus itself produces latency and may be shed and transmitted to susceptible cattle.
Maximal utilization of intramuscularly (hereinafter "IM") -administered MLV IBR vaccines has been especially hampered by the hazards of vaccine-induced abortions. That is, abortion rates as high as 60% have been reported after IM administration of some MLV IBR vaccines (Kahrs, R. F., J. Am. Vet. Med. Assoc., 171:1055-1064 (1977); and Kendrick, J. W. et al, Am. J. Vet. Res., 28:1269-1282 (1967)). In addition, with the MLV IBR vaccines currently in use, there is the danger of reversion to virulence.
In a search for safer MLV IBR vaccines, specialized vaccines have been developed (Todd, J.D. et al, J. Am. Vet. Med. Assoc., 159:1370-1374 (1971); Kahrs, R. F. et al, J. Am. Vet. Med. Assoc., 163:427-441 (1973); Smith, M. W. et al, Can. Vet. J., 19:63-71 (1979); Zygraich, N. et al, Res. Vet. Sci., 16:328-335 (1974); and Kucera, C. J. et al, Am. J. Vet. Rest, 39:607-610 (1978)). These vaccines have been found to be immunogenic and safe for IN administration to pregnant cattle and can prevent abortions in pregnant cows which have been challenge-exposed to virulent IBRV. However, they have a disadvantage in that they can only be administered by the IN route. This is because, when administered IN, one such IBR vaccine replicates to a limited extent at the lower temperature of the upper respiratory tract. However, when administered IM, the vaccine replicates poorly or not at all at normal body temperatures (Zygraich, N. et al, Res. Vet. Sci., 16:328-335 (1974)). On the other hand, another IBR vaccine is insufficiently attenuated for IM administration to pregnant animals although safe when given IN (Todd, J. D., J. Am. Vet. Med. Assoc., 163:427-441 (1973)). Furthermore, some of the vaccine strains produce mild or moderate respiratory disease even after IN administration, and they do not prevent signs of IBR following field challenge exposure (Kahrs, R. F. et al, J. Am. Vet. Med. Assoc., 163:437-441 (1973)). Vaccination by temperature-sensitive viruses does not prevent the installation of virulent virus in a latent form or the reexcretion of the virulent virus. Moreover, vaccination with temperature-sensitive viruses does not inhibit reexcretion of a wild-type strain latently carried by animals at the time of vaccination (Nettleton, P. F. et al, In: Latent Herpesvirus Infections in Veterinary Medicine, Eds. G. Whittmann, R. M. Gaskell and H.-J. Rziha (Martinus Nijhoff Publishers: Boston/The Hague/Dordrecht), pages 191-209 (1984); Straub, O. C., Comp. Immun. Microbiol. Infect. Dis., 2:285-294 (1979); Thiry, E. et al, Veterin. Microbiol. 10:371-380 (1985); and Zuffa, A. et al, Zentrabl. Veterinaermed. Reihe B., 29:413-425 (1982)).
Accordingly, neither the IM-administered MLV IBR vaccines, which are unsafe for pregnant cows, nor the MLV IBR vaccines that must be administered IN, discussed above fit comfortably into many of the current management practices. That is, vaccination of large numbers of animals by the IN route is inconvenient and potentially dangerous to animal handlers. In addition, screening to identify pregnant animals prior to immunization is often not desirable or cost effective.
III. Attenuated Properties of Thymidine Kinase-Negative Herpesvirus Mutants
Recently, temperature-resistant, thymidine kinase-negative (hereinafter "tk.sup.- ") IBR vaccines derived from the thymidine kinase positive (hereinafter "tk.sup.+ "), i.e., wild-type, Los Angeles strain of IBRV (ATCC No. VR 188) have been developed which overcome many of the problems that have limited the use of currently available vaccines (Kit, S. et al, Virol., 130:381-389 (1983); Kit, S. et al, Arch. Virol., 86:63-83 (1985); Kit, S. et al, Vaccine, 4:55-61 (1986); and U.S. Pat. Nos. 4,569,840 and 4,703,011, which articles and patents are incorporated by reference herein in their entirety)). These IBRV vaccines consist of plaque-purified IBRV isolates that replicate equally well at either 39.1.degree. C. or 34.5.degree. C. in rabbit skin, bovine tracheal cells and bovine kidney cells. Hence, they are designed "temperature-resistant". This is in contrast to those IBRV strains that are designated "temperature-sensitive", that is, those used for the IN-administered vaccines which replicate only about 10.sup.-4 to 10.sup.-7 as well at 39.1.degree. C. as at 34.5.degree. C. In addition to the ability to replicate equally well at 39.1.degree. C. or 34.5.degree. C., the tk.sup.- IBR vaccines lack the ability to produce a functional thymidine kinase enzyme (hereinafter "TK") in infected cells. In one vaccine, designated IBRV(B8-D53) (ATCC No. VR 2066) (U.S. Pat. No. 4,569,840), the failure to produce a functional TK results from a mutagen-induced mutation. With a second vaccine, designated IBRV(NG)dltk (ATCC No. VR 2112) (U.S. Pat. No. 4,703,011), the failure to produce a functional TK results from a deletion of about 400 base pairs (hereinafter "bp") from the coding sequences of the IBRV tk gene. In addition to this deletion, there is an insertion into the IBRV tk gene of a 40 bp oligonucleotide, designated NG, with stop codons in all three reading frames. The characteristics, i.e., temperature resistance and tk.sup.-, directly contribute to the superiority of these IBRVs as vaccines.
As an alternative to the above-described tk.sup.- mutagen-induced mutants and tk.sup.- deletion mutants of IBRV, embodiments of the present invention were developed. Specifically, these embodiments relate to IBRV mutants that fail to produce any functional thymidine kinase as a result of an insertion in the coding region of the IBRV tk gene without deleting any nucleotide sequences from the IBRV tk gene. Insertion mutations inactivate the function of the IBRV tk gene by disrupting normal transcription and translation of the IBRV tk gene. Based on the findings that the previously described IBRV tk.sup.- mutagen-induced mutants and tk.sup.- deletion mutants are safe and efficacious vaccines against IBR disease, it is believed that the IBRV tk.sup.- insertion mutants of the present invention will also be useful as vaccines against IBR disease. The development of this embodiment of the present invention is based in part on the description of the location of the IBRV tk gene and the nucleotide sequence thereof, and the enrichment and selection procedures developed for isolating the IBRV tk.sup.- mutants described in U.S. Pat. Nos. 4,569,840 and 4,703,011. That is, prior to U.S. Pat. No. 4,703,011, it had not been possible to develop IBRV mutants that fail to produce any functional thymidine kinase as a result of an insertion in the IBRV tk gene because in the art (1) the location of the IBRV tk gene on the physical map of IBRV DNA was not known; (2) the approximate boundaries of the nucleotide sequences delineating the coding region of the IBRV tk gene were not known; and (3) the restriction nuclease sites within the IBRV tk gene to allow appropriate insertions to be made in a cloned IBRV tk gene were not known. In addition, prior to U.S. Pat. Nos. 4,569,840 and 4,703,011, it was not known in the art what selection drugs were advantageous for enrichment and selection procedures. As a result, prior to U.S. Pat. Nos. 4,569,840 and 4,703,011, there was insufficient information to engineer and isolate an insertion mutant in the IBRV tk gene.
IV. Distinguishing Vaccinated From Infected Animals
The temperature-resistance and tk.sup.- characteristics of the IBRV mutants discussed above greatly improves their safety and usefulness as vaccines. However, the dormancy feature of IBRV still makes it difficult to effect eradication of IBR through the application of quarantine measures which are intended to prevent the spread of IBR by the isolation of IBRV-infected herds and the slaughter of IBRV-infected animals. That is, with existing MLV IBR vaccines, it is impossible to determine, by simple blood tests, whether a specific animal, which does not show symptoms of illness, is a carrier of a dormant IBRV. This is because usage of most current vaccines masks infections. Hence, since animals which appear healthy may actually be carriers and, thus, spreaders of IBRV, it is important to be able, even after vaccination, to identify infected animals and herds so as to be able to apply quarantine measures.
In addition, some countries require that imported livestock, whether for breeding, for stocking of farms, or for market, be tested and shown not to be carriers of IBRV, i.e., the animals cannot be imported unless they are seronegative for IBRV. With current killed and MLV IBR vaccines, a producer who elects to protect his animals from the diseases which accompany the stresses of shipping, or who is forced by the circumstances of IBR infection in an endemic region to vaccinate susceptible animals, finds himself at a severe economic disadvantage. This is because vaccination of the stock with current killed and MLV IBR vaccines results in a positive serological test for IBRV. Revaccination to enhance protection further increases IBRV antibody titers. As a result, the farmer's ability to export valuable livestock and to sell his stock at home is restricted and he is at a disadvantage whether he vaccinates or does not vaccinate. Hence, an IBR vaccine is needed that can be administered safely, can protect animals from disease and dormant infections caused by field strains of IBRV, has a low or nonexistent probability of reversion to virulence, and yet, does not produce a positive serological test for IBRV. Such a vaccine would allow exportation of livestock and vaccination programs to be pursued unhindered by the fear of quarantine. A producer could then minimize losses within his own herd, while animal health authorities could continue with their respective control measures.
To meet the needs discussed above, e.g., the IBRV(NG)dltk vaccine described in U.S. Pat. No. 4,703,011 was further modified to produce vaccines, such as IBRV(NG)dltkdlgIII (ATCC No. VR 2181), described in U.S. patent application Ser. No. 116,197, filed Nov. 3, 1987, which U.S. application is incorporated by reference herein in its entirety. This IBR vaccine not only fails to produce any functional TK as a result of a deletion in the IBRV tk gene but also fails to produce any antigenic IBRV gIII polypeptides as a result of a deletion in the IBRV gIII gene. The IBRV gIII gene has been found to be a useful serological marker for IBRV infections.
V. Viral Based Vectors
During the last few years, recombinant DNA technology has permitted the construction of chimeric viruses which express genetic information from more than one origin.
A variety of unique viral based vectors have been developed such as adenovirus based vectors (Ruether, J. E. et al, Mol. Cell. Biol. , 6:123-133 (1986); and Haj-Ahmad, Y. et al, J. Virol., 57:267-274 (1986)) as well as herpes simplex virus based vectors (Smith, M. et al, Proc. Natl. Acad. Sci. USA, 81:5867-5870 (1984); and Smiley, J. R. et al, J. Virol., 61:2368-2377 (1987)), Herpes saimiri virus based vectors (Desrosiers, R. C. et al, Mol. Cell. Biol., 5:2796-2803 (1985)), baculovirus based vectors (van Wyke Coelingh, K. L. et al, Virol., 160:465-472 (1987); Miyamoto, C. et al, Mol. Cell. Biol., 5:2860-2865 (1985); Smith, G. E. et al, Proc. Natl. Acad. Sci. USA, 82:8404-8408 (1985); Smith, G. E. et al, Mol. Cell. Biol., 3:2156-2165 (1983); Matsuura, Y. et al, J. Gen. Virol., 68:1233-1250 (1987); and Kang, C. Y. et al, J. Gen. Virol., 68:2607-2613 (1987)), and nuclear polyhedrosis virus based vectors (Hu, S. -L. et al, J. Virol., 61:3617-3620 (1987); and Marumoto, Y. et al, J. Gen. Virol., 68:2599-2606 (1987)).
The use of viral based vectors as vaccines is advantageous over subunit vaccines because replication of the viral based vectors within the host amplifies the amount of foreign antigen being expressed thereby, often increasing both cell-mediated and humoral immunogenic responses to the foreign antigen. In addition, the expression of foreign antigens within infected cells of the immunized host provides for post-translational modifications of the foreign antigen and thus antigen presentation more closely resembling those occurring during natural infection with the pathogen from which the foreign antigen is derived. Further, the use of safe, live-attenuated virus as vectors allows for the immunization against the pathogen from which the foreign antigen is derived.
The most extensively developed and exploited viral based vectors are the vaccinia virus based vectors (Mackett, M. et al, Proc. Natl. Acad. Sci. USA, 79:7415-7419 (1982); Panicali, D. et al, Proc. Natl. Acad. Sci. USA, 79:4927-4931 (1982); and Fuerst, T. R. et al, Mol. Cell. Biol., 7:2538-2544 (1987)). Vaccinia virus based vectors which have been described include those which are useful as vaccines for hepatitis B (Smith, G. L. et al, Nature, 302:490-492 (1983); and Cheng, K.-C. et al, J. Virol., 61:1286-1290 (1987)); rabies (Kieny, M. P. et al, Nature, 312:163-166 (1984); and Wiktor, T. F. et al, Proc. Natl. Acad. Sci. USA, 81:7194-7198 (1984)); malaria (Smith, G. L. et al, Science, 224:397-399 (1984)); human respiratory syncytial virus (King, A. M. Q. et al, J. Virol. 61:2885-2890 (1987); human parainfluenza virus type 3 (Spriggs, M. K. et al, J. Virol., 61:3416-3423 (1987)); rotavirus SA11 (Andrew, M. E. et al, J. Virol., 61:1054-1060 (1987)); influenza (Smith, G. L. et al, Proc. Natl. Acad. Sci. USA, 80:7155-7159 (1983); Smith, G. L. et al, Virol., 160:336-345 (1987)); herpes simplex virus (Paoletti, E. et al, Proc. Natl. Acad. Sci. USA, 81:193-197 (1984); Gillespie, J. M. et al, J. Clin. Microbiol., 23:283-288 (1986); and Sullivan, V. et al, J. Gen. Virol., 68:2587-2598 (1987)); vescicular stomatitis virus (Mackett, M. et al, Science, 227:433-435 (1985)); human immunodeficiency virus envelope proteins (Chakrabarti, S. et al, Nature, 320:535-537 (1986); Hu, S. -L. et al, Nature, 320:537-540 (1986); and Hu, S. -L. et al, Nature, 328:721-723 (1987)); and Friend murine leukemia virus envelope proteins (Earl, P. L. et al, Science, 234:728-731 (1986)). A vaccinia based viral vector which expresses the coding gene sequences of the PRV g92 gene has also been described (Robbins, A. K. et al, European Pat. Publication No. 0,162,738). In addition, vaccinia-based viral vectors which express host genes, such as murine interleukin-2 (Ramshaw, I. A. et al, Nature, 329: 545-546 (1987)) and murine Class I major histocompatibility complex antigen H-2K.sup.d, have been reported (Coupar, B. E. H. et al, Proc. Natl. Acad. Sci. USA, 83:7879-7882 (1986)).
Viral based vectors offer several significant advantages. First, immunization against more than one disease is possible with a single virus strain. This creates economy of production. Second, for many vaccines, two or more different modified-live viruses cannot be employed in combination in a single formulation because the replication of the viruses in the host causes mutual interference, and thereby impairs immunization. This situation is circumvented with viral based vectors because there is only a single replicating genome. Third, vaccines against causative agents of infectious disease, such as viruses and bacteria, for which vaccines have not previously been available or feasible, may for the first time be developed using viral based vectors which express the antigens of the causative agents of infectious disease. This is because the only component of the causative agents of infectious disease which is carried by the viral based vector is the gene coding for the antigen of the causative agent of disease which is responsible for eliciting immunity. Other components of the causative agents of infectious disease that are responsible for the pathobiology of the disease are eliminated from the viral based vector.
Although there is evidence that genetically engineered vaccinia viruses have reduced pathogenicity, there are several major obstacles to their general use as vaccines. First, severe complications can occur after vaccination, especially in immunodeficient individuals. Second, they are highly infectious for many animal species and humans. The insertion of genes from heterologous virus species into vaccinia-based viral vectors could alter the recombinant vaccinia virus host range or tissue tropism. Therefore, as agents, vaccinia virus based vectors pose potential health hazards. Third, there is no purpose served in vaccinating animals against smallpox, i.e., the disease that vaccinia protects against. Finally, potential recombination events between vaccinia and indigenous animal pox viruses might regenerate virulence of the vaccinia virus which will cause smallpox disease in humans.
IBRV-based viral vectors have distinct advantages over vaccinia-based viral vectors for the vaccination of cattle because they (1) protect cattle against the important bovine diseases of IBR and IPV; and (2) are host-limiting, i.e., they do not infect humans.
In embodiments of the present invention, IBRV has been utilized as the basis for viral based vectors. IBRV is a typical alpha herpesvirus with a genome consisting of linear double-stranded DNA molecules approximately 135-140 kilobases (hereinafter "kb") in size. Like vaccinia and like other herpesviruses, IBRV can tolerate nucleotide sequence deletions of 4 kb or more, and can tolerate foreign DNA insertions of 5-10 kb or more.
Prior to U.S. Pat. No. 4,703,011 and U.S. patent application Ser. No. 116,197, filed Nov. 3, 1987, now U.S. Pat. No. 4,992,051 it was not possible to develop IBRV-based viral vectors because there was no knowledge of the location of suitable, insertion sites, i.e., non-essential IBRV genes, which could be employed for the insertion of foreign genes. U.S. Pat. No. 4,703,011 and U.S. patent application Ser. No. 116,197, filed Nov. 3, 1987, however, identified the location of the IBRV tk and IBRV gIII genes on the physical map of IBRV DNA and demonstrated that they were not essential for virus replication in cultured cells. Hence, suitable insertion sites for foreign genes became known for the first time. Furthermore, U.S. Pat. No. 4,703,011 and U.S. patent application Ser. No. 116,197, filed Nov. 3, 1987, now U.S. Pat. No. 4,992,051 described for the first time the nucleotide sequences of the coding regions, the promoter regions, the translation start and stop signals, and the polyadenylation signals of the IBRV tk and IBRV gIII genes.
In the present invention, the isolation of IBRV DNA fragments containing IBRV gene promoters and the ligation of IBRV promoters to the coding nucleotide sequences of foreign genes has been described for the first time. Further, it has been determined for the first time in the present invention that in IBRV-based viral vectors, the foreign gene can be expressed by a foreign gene promoter and does not require an IBRV promoter for expression. Thus, for the first time in the present invention, it has been possible to develop IBRV-based viral vectors.

Infectious bovine rhinotracheitis virus insertion mutants, vaccines containing same, and methods for the production of same


A guidewire lumen for a catheter includes a tubular portion and a sleeve bonded over less than an entire length of the tubular portion. The tubular portion is formed of a first material and the sleeve is formed of a second material. The second material may bond better to certain materials than the first material.

The present invention relates to catheters and catheter components and, more particularly, to catheters and catheter components including guidewire lumens with sleeves.
Catheters used to treat, e.g., blocked arteries in coronary, peripheral, and neurovascular fields are typically guided to a treatment site by riding over a guidewire. Although the guidewire is sometimes coated with a friction-reducing material such as TEFLON, there is generally some friction when a plastic catheter is pushed over the wire.
In the past, in balloon catheters, polyethylene was used as the balloon material in the catheter. This allowed the use of low friction, High Density Polyethylene (HDPE) as the lumen for the guidewire. A low profile heat bond could be performed at the distal tip of the balloon and the guidewire lumen to allow for a smooth transition and a soft tip.
As more advanced and stronger materials have been developed for the balloon, such as Polyester (PET), Nylon, and Acrylon (Acrylonitrile), a need for an alternative to HDPE has arisen. HDPE as a single material cannot be heat bonded to materials such as Polyester, Nylon, and Acrylon. Some of the materials that can be bonded to Nylon balloons include Polyether Block Amide (PEBAX) and Nylon, however, these materials tend to have higher surface friction than HDPE. One solution has been to coextrude an inner layer of HDPE or TEFLON and an outer layer of some other material, such as PEBAX. This is more costly than an HDPE extrusion, and the coextrusion can result in delamination. Alternatively, an adhesive bond has been used. However, adhesive bonds tend to be undesirably stiff and have a relatively high profile.
Materials with low surface friction such as HDPE, and various fluoropolymers such as PolyTetraFluoroEthylene (PTFE) (also known as TEFLON as manufactured by DuPont), TetraFluorEthylene-Perfluorpropylene (FEP), and PerFluoroAlkoxy (PFA), cannot be heat bonded to many modern balloon materials and are difficult to process. Materials presently used as the guidewire lumen for Nylon balloons are commonly Polyether Block Amide (PEBAX), Nylon 11, Nylon 12, or blends of these materials. Materials used for PET and Acrylon balloons are Hytrel and PET/Polyurethane blends. Polyurethane balloons used for neuro applications also commonly use polyurethane or PEBAX inner wire lumens. All of these materials have high surface frictions at body temperature and have the potential to interfere with guidewire movement.
It is desirable to provide a material suitable for use in a catheter having a low surface friction and that is flexible and easy to process. It is particularly desirable to provide such a material for use in connection with a guidewire lumen.
In accordance with an aspect of the present invention, a guidewire lumen for a catheter comprises a tubular portion and a sleeve disposed over less than an entire length of the tubular portion, the tubular portion being formed of a first polymer and the sleeve being formed of a second polymer, the second polymer comprising one or more of a polyamide, a nylon, a polyether block amide, and polyurethane.
In accordance with another aspect of the present invention, a guidewire lumen for a catheter comprises a tubular portion formed of a first material and a sleeve formed of a second material disposed around part of the tubular portion, and a metallic marker band disposed around a portion of the tubular portion, the sleeve being disposed over the marker band and extending from proximate a distal end of the tubular portion to a point proximal of and proximate the marker band.
In accordance with another aspect of the present invention, a method of making a catheter comprises providing a sleeve over less than an entire length of a tubular portion of a guidewire lumen, the tubular portion being formed of a first material and the sleeve being formed of a second material, providing a marker band over the tubular portion and beneath the sleeve, and bonding the sleeve to a catheter component.
In accordance with another aspect of the present invention, a catheter comprises a guidewire lumen comprising a tubular portion and proximal and distal sleeves disposed over less than an entire length of the tubular portion, the tubular portion being formed of a first material and the sleeves being formed of a second material, and a metallic marker band disposed between the distal sleeve and the tubular portion, a balloon bonded to the distal sleeve, and a catheter shaft bonded to the proximal sleeve.

Catheter with guidewire lumen with tubular portion and sleeve


A catheter includes a catheter body having a proximal end, a beveled distal end, and a lumen therethrough. The beveled distal end defines an elliptical port for releasing contrast or other media through the lumen and from the elliptical port. The catheter may also be used delivering devices or for aspirating or extracting materials from the vasculature or other body lumens. A fixed guidewire extends distally from the distal end of the catheter body, typically from the distal-most edge of the elliptical port. The fixed wire is typically malleable so that it can be manually formed into a desired shape. The elliptical port may be flat or concave.

1. Field of the Invention
The present invention relates generally to medical devices and methods. More particularly, the present invention is directed at guide wires and their incorporation into diagnostic and therapeutic (multipurpose) catheters.
Currently, diagnostic catheters are steered by a first wire (typically referred to as a moveable guidewire) that is disposed in a lumen running the entire catheter length, typically 90-100 cm. The first wire is longer than the catheter and extends distally from the catheter tip by a variable length, usually from 5-7 cm. The diagnostic catheters are navigated "over the wire" (OTW) to a target vessel, typically a coronary or cerebral artery in an angiography procedure. The purpose of the wire is to steer the catheter as it is advanced through the artery. The wire is advanced first, and the catheter is then advanced over the slides over wire which provides a track for guiding the catheter. This procedure is repeated until the catheter reaches the desired or "target" location, and the wire is then pulled back in the case of an angiography catheter to open the lumen for introducing contrast media.
After the initial angiography or other diagnostic procedure is complete, a balloon or other therapeutic catheter may be "exchanged" for the diagnostic catheter by replacing the first wire with a longer, typically 260-300 cm, exchange wire. The diagnostic catheter is withdrawn over the exchange wire, and the therapeutic catheter then advanced over the exchange wire. The exchange wire must be sufficiently long to allow the physician to be able to grasp some portion of the wire as the diagnostic catheter is withdrawn as well as when the therapeutic catheter is advanced.
Having the entire length of the first wire present in the diagnostic catheter can be disadvantageous in several ways. For example, the wire reduces the flexibility of the catheter making the diagnostic catheter difficult to navigate through tortuous anatomy. Additionally, the space between the inner diameter (ID) of the diagnostic catheter lumen and the outer diameter (OD) of the first wire creates a "shelf". This shelf can "catch" on the ostium of branch vessels as they take off from the main vessel along the catheter's course.
Currently guidewires used in diagnostic procedures have an outside diameter (OD) from 0.035 inch to 0.038 inch, reducing the flexibility of the diagnostic catheter as it is advanced through the vasculature. One reason for using such larger, stiffer wires is to decrease risk of the "shelving effect" between the catheter and the wire. Using a larger diameter wire reduces the spacing between the catheter lumen's ID and the wire's OD which in turn reduces the height of the shelf and the risk that catheter will engage branch vessels as the catheter is advanced. Such larger diameter wires, however, have the disadvantage that they are less flexible, making navigation of the wires and catheters even more difficult.
A further difficulty with conventional angiography and other diagnostic catheters arises when the first wire is pulled back during advancement of the catheter, Such pull back generates a negative pressure (similar to pull back of a plunger in a syringe) which can release air bubbles from the catheter lumen. The air bubbles can travel distally into the blood stream creating air emboli and potentially causing cause strokes.
Two techniques are commonly used to mitigate air bubbles from migrating distally when the wire is removed: The first technique is known as "double flush" technique in which aspiration with a syringe is performed twice, before establishing anterograde flow; after the second aspiration, the catheter is flushed with heparinized saline and contrast dye. The second technique uses continuous heparinized saline infusion, and when the wire is removed, the rotatory hemostatic valve (RHV) is left open allowing back bleeding; this retrograde bleeding will remove the air bubbles, then the RHV is flushed with saline, and finally anterograde flow is established. Both these techniques add complexity and risk to the procedures.
Most wires have an atraumatic "J" tip, in order to deflect the wire away from vessel walls, and to prevent the wire from dissecting the vessel wall when resistance is found. A less common wire has a straight tip but is malleable, giving the operator the ability to reform the tip, into a desired shape, based on the architecture of the vessel that attempted to be catheterized and to facilitate the a-traumatic catheterization of the vessel. Once the wire "makes a curve", the catheter is advanced OTW to the desired location.
With current technology the proximal end of the wire is manually rotated by hand with a "pill-roll" finger movement or using a torque device, a collet, that facilitates the necessary grasp to make a clock and counter-clock rotation of the wire. With current diagnostic catheter technology, it is also necessary to pull the wire out prior to the contrast injection which is necessary in order to opacify the target. Both these steps complicate current angiography protocols.
A majority of diagnostic catheters have angled tips, called multipurpose (MP) catheters. A 45° degree MP tip is bent at a 45° degree angle relative to the central axis of the catheter body. The purpose of an angled tip is to allow engaging the origin of larger vessels and then to advances the wire from within. Once the target has been reached, the catheter can slide over the wire. Ideally, MP catheter tips are left along the axis of the target vessel. On the other hand, if a MP catheter is in a straight segment, the angled tip will be against the wall, as shown in FIG. 1, with the potential to cause a dissection to the vessel wall, especially if the wire is advanced forward.
For these reasons, it would be desirable to provide improved guide wire structures and methods for their use in introducing angiography and other vascular diagnostic and therapeutic catheters. It would be particularly desirable to provide diagnostic catheter structures and methods for their use which can eliminate the need to periodically pull back the guide wire as the catheter is advanced, thus simplifying the procedure and lessening the risk of introducing air embolism. It would further be desirable to eliminate any need for more than one lumen in the diagnostic catheter. At least some of these objectives will be met by the inventions described hereinafter.
2. Description of the Background Art
The disclosures described below are relevant background to the present invention:
U.S. Pat. No. 5,114,414 describes a system that includes a multi-lumen catheter. One of those lumens is closed at the distal end, with an "antenna" that comes out the distal closed end. The stated purpose of the wire is to protect the arterial lumen. The other lumens are multipurpose. i.e. to host a wire, instruments, or the like. Having multiple lumens can lead to an undesirable overall increase in the diameter of the catheter.
U.S. Pat. No. 8,764,724 describes a diagnostic or aspiration catheter (FIGS. 7A, 7B and 8) with an obliquely inclined tip having a wire lumen 92 fixed thereto and a guide wire extending therethrough. The patent proposes a multi lumen catheter for coronary application. My invention describes a single lumen catheter. One of the elements of this co-axial system described here includes a beveled catheter on both ends distal and proximal. The proximal segment of the double beveled catheter is attached to a wire that is embedded for the entire length. The wire does not arise from the beveled tip, my invention describes a wire embedded only on the distal tip of a beveled catheter, the one that is presented here comes from a separate element from one of the lumens within the coaxial system. Shows a suction catheter (FIGS. 7A, 8) with an obliquely inclined tip having a wire lumen 92 fixed thereto and a guide wire extending therethrough. The beveled tip increases the cross sectional diameter of the catheter.
U.S. Pat. No. 7,224,250 describes a two lumen aspiration catheter with one lumen having a beveled tip and a second, shorter lumen, providing a rapid exchange system where the wire is not part of the system. There is a shorter catheter that is glued to the distal end of the aspiration catheter; this second lumen allows the passage of a wire. These catheters are advanced to a target location after an initial catheter reaches the target. The initial catheter is then withdrawn and replaced with a second catheter.
U.S. Pat. No. 8,850,960 describes a beveled catheter for arterial puncture like a needle, followed by the insertion of a dilator. The catheter uses a wire that travels within the entire lumen of the catheter but which is not embedded. The purpose is mainly for access and not for navigation aspiration or radiographic contrast injection.
A stent on a wire is described in Sarno et. al. (2010) EuroIntervention 6:413-417. The wire is attached the entire length of the stent, and the device is not intended for primary navigation and requires a separate guiding catheter. The "stent on a wire" does not have a beveled tip.
FIG. 1 shows a prior art MP catheter in a straight section of an artery with a distal tip of the catheter urged against the arterial wall. A magnification in the lower left corner shows deformation of the wall by the catheter tip.

Delivery catheter with fixed guidewire and beveled elliptical port


A virtual jog wheel for navigating a set of media elements is disclosed. A graphical user interface including the virtual jog wheel and a set of media elements is provided. A command from a user corresponding to a rotational movement of a touch object relative to the virtual jog wheel is identified. In response to the command, a user may navigate from a first position in a first media element of the set of media elements to a second position in a second media element of the set of media elements.

Users watching videos, viewing images, or listening to music on a computing device (e.g., a mobile phone or a tablet) often have the desire to change a current position in the playback of the underlying content (e.g., the video, photos, or audio). The current playback position within the media (i.e., the playback position) is often controlled by a user via an interaction with a slider bar (i.e., a seek-slider bar or a time scrubbing bar) whereby a user may change a current playback position by moving or sliding an indicator or pointer along the slider bar to a new playback position. Certain touchscreen-based slider bars are horizontally arranged and require a user to move a touch object (e.g., a finger) in a vertical direction in order to control the scrubbing speed (e.g., the rate of movement of a pointer corresponding to a playback position).
Frequently, multiple media elements (e.g., individual audio and/or video files) are presented to the user in a playlist. In such instances, the user may use a slider bar to control the playback position within a single media element in the playlist, but may not interact with the slider bar to switch the playback position among the multiple media elements.

This patent is subject to a terminal disclaimer.

Media element navigation using a virtual jog wheel


Belt weatherstrip moulding for motor vehicles or other motor vehicle trim may be made of separate inner and outer components. The inner component may be a base component which is extruded in a flexible material such as an elastomeric material which may be rubber or rubbery materials and which partially envelops an elongate core which is rigid with respect to the extruded material. Preferably the core is aluminum or less preferably stainless steel, galvanized steel or zinc coated steel or it may be a rigid thermoplastic material. The elongate core has an exposed face for attachment to the outer moulding. The outer component is an outer decorative skin and is an injection moulding, preferably polyurethane, although other plastics material may be used. The inner and outer mouldings are adhered together through double sided adhesive tape. It is possible to attach the composite moulding to a vehicle body by means of only one fixed mounting and a number of other mountings which allow relative movement between the vehicle body and the composite trim member to compensate for relative differences in expansion and contraction between the vehicle body and the trim.

1. Field of the Invention
This invention relates to exterior decorative trim for vehicles, the trim having a stiffened core. The invention particularly relates to belt moulding weatherstrip for use in adjacent moveable or stationary windows.
2. Description of the Prior Art
Exterior elongate trim for vehicles which has been formed of a combination of a stiffened elongate portion and a softer flexible elongate portion. This has caused some difficulties in manufacture. This is especially true when it is desired to provide the outer visible surface of the trim with a high gloss finish.
One method of making trim for this purpose is to extrude a moulding, e.g. of rubber, over an elongate metal core to totally encapsulate it. The resultant moulding which is stiffened by the metal core may be applied to the body of the automobile by any convenient method. It may be possible to apply a second moulding part over this first moulding encapsulating the metal core to provide any decorative finish. Such metal moulding parts are usually fixed by riveting, stapling, screwing or other conventional means.
It has also been proposed to form a two-part trim in which the first extrusion encapsulating the metal core is used as a base for an outer decorative trim part which is formed thereon to by injection moulding.
Still further it has been proposed to co-extrudea base moulding over a metal core and provide an outer decorative skin.
This last described system, while providing trim of a acceptable quality, is very expensive since defects noticed in final operations in the outer decorative trim may involve discarding the whole of any defective two-part moulding.
Generally, difficulties have been encountered in providing a base moulding having a stiffened elongate portion and a more flexible portion which moulding is easily and economically attachable to a decorative finished portion. Problems have also been encountered in the provision of a high gloss finish of the top decorative portion which withstands the weathering over a period of time. These problems are accentuated where belt mouldings are concerned since belt mouldings require a very flexible lip adjacent to an automobile window which seals against the window while, when the window is a movable window, allowing sliding of the window against it.
The present inventors have addressed the problems of providing an improved, economically manufacturable belt weatherstrip moulding which will withstand weathering of its decorative outer surface and will withstand temperature changes which tend to cause expansions and contractions along the length of the moulding.


A method of suppressing interference in a communication sent over a channel includes assessing characteristics of channel-induced distortion in a channel, and applying pre-distortion to a signal sent over the channel. The pre-distortion is based on the assessed characteristics of the channel-induced distortion.

Field
This invention relates to handling interference in power and communications systems. More particularly, the invention relates to methods and systems for suppressing interference in communication signals and power signals transmitted over electrical power lines.
Description of the Related Art
Electrical power lines are sometimes used to carry signals and data in addition to electrical power. A power line communication (PLC) system, for example, may allow end-user devices and utilities to transmit data and enable devices to respond to commands. One application for power line communication is in a "smart grid". The term "smart grid" may be used to refer to a control system that integrates digital computing and communication technologies and services with the power-delivery infrastructure, such as contemplated in the Energy Independence and Security Act of 2007.
Power line communications, such as those used in smart grid applications, may not function properly if reliable communications are not available among users (for example, among grid operators, utilities, end users, and electrical devices). Utilities increasingly require improved communications methods & technologies to collect data and computing power and software to visualize and control grid operations in real time.
One problem that may be encountered in PLC systems is interference. A low-frequency power line channel tends to be a harsh, complex, reactive environment for any form of communications. The power signal itself (the 60 Hz "fundamental") may produce a form of distortion that is problematic for secondary signals (such as communication signals) which are introduced into the channel. For example, the reactive nature of the channel, combined with the relative heft of the primary stimulus (the fundamental, or the power signal itself), may produce a form of channel-initiated modulation which may have a detrimental effect on such secondary communication signals. This channel-initiated modulation may express itself in the combined channel (containing the power signal, the communication signal, and other noise) as a form of noise which is time-synchronous with (or "coherent with") the power signal and which affects all signals in the channel. This time-synchronous or coherent noise may also be referred to as "images" or "ghosts" or "side lobes". The coherent noise may be perceived as a recursive replication of the original communication signal, a recursive replication of some component of the original communication signal, or periodically recurring energy which distorts the communication signal. Image signals may be particularly problematic for communications scenarios which rely on multiple closely spaced, narrowband subcarriers (for example, narrowband frequency division modulation or similar approaches).
Transmission of data via an active power line is a difficult task. Among other things, the pre-existing power signal may cause a number of problems in the system. These problems may include pseudo-stationary interference from harmonics of the fundamental, other forms of synchronous noise, or a form of "blowback" into the data transmitter from the fundamental and harmonics, among others. The structure of the power line network may also interact with low frequency secondary signals that are introduced to the network for the purposes of communication. This interaction may appear as a form of amplitude modulation of the communication signal. The amplitude modulation envelope may be time-synchronous or coherent with the fundamental. The distorting amplitude modulation envelope may be imposed on any/all secondary signals in the channel. This type of channel-induced distortion may be problematic for data communications because amplitude modulation tends to create a proliferation of harmonically-related images of the communication signal or components of the communication signal. As image signals proliferate in the channel, the availability of idle or clear spectrum for additional subcarriers may be drastically reduced, and thus the placement of those subcarriers may become difficult.

Suppression of interference in power and communications signals


An energy degrader includes: a damping unit that attenuates energy of incident charged particles and has a thickness changing stepwise or continuously according to a position of a two-dimensional coordinate system within a plane crossing a traveling direction of charged particles; and a driving unit that performs translational driving of the damping unit in first and second axial directions that are directions of two axes crossing each other in the two-dimensional coordinate system.

1. Technical Field
The present invention relates to an energy degrader to attenuate the energy of charged particles and a charged particle irradiation system including the same.
2. Description of the Related Art
Equipment that irradiates a patient with charged particles, such as proton beams, to perform cancer treatment is known. This kind of equipment includes a cyclotron to accelerate ions (charged particles) generated by an ion source, a transport line to transport the charged particles accelerated by the cyclotron, and a rotatable irradiation device (rotating gantry) to irradiate the patient with charged particles from an arbitrary direction.
In a particle beam irradiation device disclosed in the related art, a depth-direction position of the charged particle beam that reaches the inside of an irradiation object is controlled by attenuating the energy of the charged particle beam accelerated by a synchrotron (accelerator) using a range shifter. This range shifter is formed so as to have a thickness changing in a stepwise manner, and controls the position in a depth direction by making the charged particle beam pass through a specific stage of the stages formed in a stepwise manner.
In the technique disclosed in the related art, the attenuation of energy is changed by changing the passing position of the charged particle beam by driving the range shifter in one axial direction.

Energy degrader and charged particle irradiation system including the same


One embodiment relates to a low intermediate frequency (IF) receiver. The low-IF receiver includes an analog front end that is configured to receive a modulated IQ data signal and provide an in-phase signal and a quadrature signal, where the in-phase signal is phase shifted by approximately 90° relative to the quadrature signal. The low-IF receiver further includes a digital processing block, and a single path that provides only one of the in-phase signal and the quadrature signal to the digital processing block. Other receivers and methods are also disclosed.

Several trends presently exist with regards to wireless communication devices. For example, in comparison to previous generations of wireless devices, modern wireless devices are more compact, more affordable, and have longer battery lifetimes. While consumers may largely take these trends for granted, these trends are the result of significant engineering efforts.
To communicate with other devices, many wireless devices include receivers. These receivers are typically included in chip sets that enable wireless communication via one of several communication standards, such as Bluetooth, Digital Enhanced Cordless Telecommunication (DECT), and numerous others. Because these chip sets are used commonly in cell phones, music players, personal digital assistants (PDAs), etc., it is desirable for the chip sets to be relatively compact and efficient, thereby providing lower cost, higher performance products in a smaller footprint.
In recent years, one way in which designers have tried to deliver compact and efficient chipsets is by including zero intermediate frequency (IF) receivers. A zero IF receiver enables direct conversion of analog radio frequency (FREQ) signals to a digital baseband. This typically reduces the component count, and may correspondingly limit the footprint and cost of the chipset. By reducing the number of components, zero IF receivers also simplify the supply chain and improve manufacturing yield.
While zero-IF receivers offer a more compact chipset, technical barriers often limit the extent to which such receivers can be used in modern communication systems. For example, because a local oscillator signal (LO) in these receivers is the same as the RF frequency, the LO signal may leak from the receiver to the antenna, which can cause interference with other receivers on the same frequency-band. Also, DC offset, which comes from the self-mixing of LO leakage, may seriously deteriorate the SNR (Signal Noise Ratio).
One type of receiver that limits both of these shortcomings (i.e., LO leakage and DC offset) is a low-IF receiver. In low-IF receivers, the received RF frequency is down-converted to a low, but non-zero IF, before being down-converted to the baseband. Thus, the down-conversion from the received RF frequency to the baseband will have one or more IFs, where each IF corresponds to a separate stage in the receiver. Due to the fact that these separate stages are relatively area intensive, conventional low-IF receivers have a relatively large footprint.
In order to continue to meet and exceed consumers' growing expectations with regards to compactness, affordability, and battery life; improved low IF receivers are needed. Ideally, these improved low-IF receivers will provide relatively high-performance in a relatively small footprint.


The ink of the invention comprises a vehicle and a colorant. The colorant is a water-insoluble pigment that has been chemically modified to be water dispersable by addition of functional groups to the surface of the pigment resulting in water soluble colorant particles. The performance of these pigments is improved by the addition of specific functional groups which provide improved black to color bleed control and high waterfastness.

Ink-jet printing is a non-impact printing process in which droplets of ink are deposited on print media, such as paper, transparency film, or textiles. Low cost and high quality of the output, combined with relatively noise-free operation, have made ink-jet printers a popular alternative to other types of printers used with computers. Essentially, ink-jet printing involves the ejection of fine droplets of ink onto print media in response to electrical signals generated by a microprocessor.
There are two basic means currently available for achieving ink droplet ejection in ink-jet printing: thermally and piezoelectrically. In thermal ink-jet printing, the energy for drop ejection is generated by electrically-heated resistor elements, which heat up rapidly in response to electrical signals from a microprocessor to create a vapor bubble, resulting in the expulsion of ink through nozzles associated with the resistor elements. In piezoelectric ink-jet printing, the ink droplets are ejected due to the vibrations of piezoelectric crystals, again, in response to electrical signals generated by the microprocessor. The ejection of ink drop-lets in a particular order forms alphanumeric characters, area fills, and other patterns on the print medium.
Inks useful in ink-jet printing are typically composed of either pigments or dyes. Pigments are very small insoluble solid colorant particles wherein the molecules are strongly associated with one another through intermolecular forces such as Van der Waals attraction, pi-pi interactions or hydrogen bonding. These forces of attraction prevent solvation of the molecules by common solvents such that they cannot form solutions like their dye counter-parts. Conventionally, pigments are used in printing inks by suspending them in a liquid medium using a high-energy dispersion process with the aid of dispersing agents. One disadvantage of using pigments is that their dispersions are inherently thermodynamically unstable and eventually the pigment particles agglomerate to larger particles that tend to settle. Moreover, pigments lead to the inks taking a relatively long time to dry on the media, which in turn leads to increased opportunity for the ink to run or smear when subjected to moisture or water; the degree of water resistance is called "waterfastness". Further, the tendency of one color of ink to run into the adjacent color is know at "bleed". This is most apparent with black ink bleeding into color inks. Several methods have been employed by ink formulators to achieve bleed control to varying degrees of success. Many pigmented inks possess one or more of the foregoing properties. However, few ink compositions possess all of those properties, since an improvement in one property often results in the degradation of another. Thus, inks used commercially represent a compromise in an attempt to achieve a pigmented ink evidencing at least an adequate dispersibility and performance in each of the aforementioned properties.
Accordingly, investigations continue into developing ink formulations that have both good dispersibility and improved properties such as improved bleed control and good waterfastness all without sacrificing performance in other necessary properties.

Superior waterfastness and bleed control with specifically treated pigments for ink-jet printing


A merchandise sensor for protecting an item of merchandise displayed on a merchandise display security device from theft includes sensor electronics and a sensor element operably coupled to the sensor electronics. The sensor element provides an output value in an initial stable state before an interaction state and in a subsequent stable state following the interaction state. The sensor electronics compares the output value of the sensor element in the subsequent stable state and the output value of the sensor element in the initial stable state to determine whether a change in the output value indicates an alarm condition. In the event that the output value of the sensor element in the subsequent stable state is not within a predetermined tolerance bandwidth of the output value of the sensor element in the initial stable state, the sensor electronics activates an alarm in response to the alarm condition.

It is common practice for retailers to display relatively expensive items of merchandise on a merchandise display security device, such as a display stand, an alarm module, a security fixture, and the like. The security device typically displays an item of merchandise so that a potential purchaser may readily view and evaluate the features and operation of the item before deciding whether to make a purchase. The item of merchandise is typically attached to a sensor that is secured on the merchandise display security device so as to prevent, or at least deter, theft of the item. The security device, the sensor, or both, may also include an audible and/or visible alarm that is activated to alert security personnel in the event of a possible theft.
Existing merchandise sensors monitor and determine the absolute state of attachment of the item of merchandise to the sensor. In other words, the sensor monitors and determines whether the item of merchandise is attached to the sensor (i.e., a "secure" or "non-alarm" condition) or whether the item of merchandise is not attached to the sensor (i.e., an "unsecured" or "alarm" condition). An alarm is activated in the event that the sensor determines an "unsecured" or "alarm" condition. As a result, the sensor is required to continuously monitor and determine the state of attachment of the item of merchandise to the sensor. Continuous absolute state sensing, however, has the specific disadvantages of producing an unacceptable number of false alarms and requiring greater power consumption. Furthermore, removable components of the item of merchandise typically must be attached to and monitored by a separate sensor. The use of multiple sensors complicates installation of the item of merchandise on the merchandise display security device and requires the retailer to maintain an inventory of different sensors. False alarms and multiple obtrusive sensors may negatively impact the experience of a potential purchaser interacting with the item of merchandise, and thus, can adversely impact sales of the item.
Accordingly, there exists an unresolved need for a sensor adapted for attachment to an item of merchandise to protect the item from theft that overcomes the disadvantages of existing merchandise display security device sensors. There exists a further, and more particular, need for a merchandise sensor that does not continuously monitor and determine an absolute state of the attachment of the item of merchandise to the sensor. There exists a further specific need for a merchandise sensor adapted for attachment to an item of merchandise and configured for use with a merchandise display security device that reduces the number of false alarms, reduces power consumption and does not require the use of a separate sensor to monitor a removable component of the item of merchandise.

Merchandise sensor and method for protecting an item of merchandise


An electroacoustic transducer system for converting sound waves propagating from a musical instrument drum to an electric signal is generally provided. The system includes a housing, an electroacoustic transducer, and a cover. The housing includes a concave inner surface and a convex outer surface. In addition, the housing defines a housing cavity with a mouth. The electroacoustic transducer is disposed in the housing cavity and faces outwardly from the concave inner surface and towards the mouth to receive sound waves propagating from the drum. The electroacoustic transducer receives and converts the sounds waves in the housing cavity to the electric signal. The cover has a generally planar outer surface and extends over the mouth to at least partially enclose the electroacoustic transducer.

1. Field of the Invention
This invention relates to an electroacoustic transducer system for a musical instrument drum.
2. Background Art
A dynamic microphone is an instrument having a transducer with a diaphragm to convert mechanical energy of sounds waves into an electric signal. Many microphones are specifically designed to pick up a sound from a musical instrument within a particular frequency range. For example, some microphones are specifically designed to pick up a low-frequency sound from a drum, such as a bass drum, a snare drum, tom-tom drum, a bongo drum, etc. Further, various attempts have been made in an effort to improve the sound quality of microphones. However, many microphones produce an electric signal that distorts or inaccurately reproduces the low-frequency sound that a drum generates.
Prior art patents include U.S. Pat. Nos. 7,256,342; and 7,297,863; and U.S. Published Patent Application Nos. 2004/0159018A1; 2002/0083622; and 2001/0003876.


A method of forming a rotary cutting die includes the following steps. A curved cutting rule transfer plate including an inner surface and an outer surface is provided. A cutting rule channel is formed in the transfer plate, and defines a predetermined design. A cutting rule having a cutting edge and a support edge is placed in the cutting rule channel. The support edge of the cutting rule extends from the inner surface of the transfer plate. A translucent rotary die place is formed on the inner surface of the transfer plate. The support edge of the cutting rule extends into and is supported in the rotary die plate. The transfer plate is then removed from the rotary die plate.

The present invention relates generally to the field of rotary cutting dies, and more particularly to an improved method and apparatus for making and using such dies.
Rotary cutting dies have been manufactured and used for numerous years. Conventionally, rotary cutting dies are formed from an opaque, resinous die plate material supporting a metallic cutting rule. The cutting rule extends above the surface of the resin die plate and defines a cutting design. The design created by the metallic cutting rule is employed to cut, score or perforate material, such as paper, cardboard or the like, through the rotary cutting process.
Usually, rotary cutting dies are sized to be mounted either on discrete sections of a rotary cutting machine die cylinder or along the entire surface thereof. To accommodate either type of die, the die cylinder typically contains a number of receiving holes spaced at pre-determined intervals. The receiving holes are positioned in an array along the die cylinder, and are configured to receive screws or other fasteners that extend through the die to affix the die to the die cylinder. Mounting holes are bored into the cutting die to align with the receiving holes in the die cylinder. The rotary cutting die is thus aligned and positioned on the die cylinder to reflect the predetermined pattern for the cutting, scoring or perforating process.
Because the die plate of the rotary cutting die is normally formed from an opaque material, the precise hole placement required to properly mount and align the cutting die on the die cylinder cannot be readily determined and must be obtained by approximation or guess. In an attempt to solve this alignment problem, a guide bar, having guide holes spaced along its longitudinal axis to match the spacing of the receiving holes in the die cylinder, has been used. The guide bar is placed along the top surface of a rotary cutting die while the cutting die is held in place over the die cylinder. The guide bar is extended across the cutting die and the die cylinder to indicate the position of the receiving holes beneath the cutting die provided in the die cylinder. By aligning the guide holes in the guide bar with the receiving holes in the die cylinder, the position of the mounting holes required to be bored or drilled into the cutting die can be more easily determined. Subsequently, the mounting holes are drilled in the cutting die and the cutting die is mounted on the die cylinder, as described above. While the guide bar has produced satisfactory results, inaccuracies in locating the receiving holes still frequently occur.
Inaccurate alignment and positioning of mounting holes may be occasionally remedied by re-drilling or otherwise forming the holes without unduly affecting or jeopardizing the integrity of the cutting die. Often, however, inaccurate mounting hole positioning in the cutting die results in the cutting die being ruined, necessitating a new cutting die being formed. When cutting dies are scrapped, significant overhead costs and down time are incurred. Moreover, inaccurate mounting hole positioning increases production costs and lowers plant productivity.


An organic light emitting display device is presented which prevents water from penetrating through an outermost side of a display panel, thereby enhancing reliability of first thin film transistors (TFTs). The organic light emitting display device includes a base substrate, a first buffer layer disposed on the base substrate, a TFT disposed on the first buffer layer in a display area, a second TFT disposed on the first buffer layer in a non-display area, an organic light emitting diode (OLED) disposed on the first TFT, and an encapsulation layer disposed on the OLED, the second TFT, and the first buffer layer. The first buffer layer and the encapsulation layer each include the same material, for example, silicon oxynitride (SiON).

Field of the Invention
The present invention relates to an organic light emitting display device, and more particularly, to an organic light emitting display device for enhancing reliability of thin film transistors.
Discussion of the Related Art
As the times advance to the information-oriented society, flat panel display (FPD) devices which have good characteristics such as thin profile, lightness, and low power consumption are increasing in importance. Examples of FPD devices include liquid crystal display (LCD) devices, plasma display panels (PDPs), organic light-emitting display devices, etc. Recently, electrophoretic display (EPD) devices are also being widely used as one type of FPD device.
In the flat panel display devices, LCD devices and organic light emitting display devices including a thin film transistor (TFT) have advantageous properties in resolution, color display, and image quality, and thus are commercialized as display devices for notebook computers, tablet computers, and desktop computers.
In particular, organic light emitting display devices are self-emitting devices, and have low power consumption, a fast response time, high emission efficiency, high luminance, and a wide viewing angle. Therefore, organic light emitting display devices are attracting much attention as next-generation flat panel display devices.
A related art organic light emitting display device includes an organic light emitting display panel, a timing controller, a gate driver, and a data driver. A plurality of gate lines and a plurality of data lines are provided in the organic light emitting display panel, and a plurality of emission parts are respectively provided in intersection areas of the gate lines and the data lines. The timing controller outputs a gate control signal for controlling a gate driver and a data control signal for controlling a data driver. The gate driver sequentially supplies a scan pulse to the gate lines in response to a gate control signal input from the timing controller. The data driver converts image data, input from the timing controller, into analog data voltages and supplies the analog data voltages to the data lines. The gate driver and the data driver are manufactured independently from the organic light emitting display panel and are connected to the gate lines and the data lines in a tape automated bonding (TAB) type.
However, when the gate driver and the data driver are separately manufactured and are connected to the display panel like the related art, a volume of the organic light emitting display device increases, and moreover, the weight of the display device increases. Therefore, recently, the organic light emitting display device is manufactured in a gate-in panel (GIP) structure where the gate driver is built into one side of the display panel. However, in the organic light emitting display device having the GIP structure, the characteristic of TFTs built into the gate driver is degraded due to hydrogen which penetrates through an outer side of the display panel. Also, reliability of a device is degraded due to hydrogen within the display panel.
The above-described background is possessed by the inventor of the application for deriving the invention, or is technology information that has been acquired in deriving the invention. The above-described background is not necessarily known technology disclosed to the general public before the application of the invention.


A top vacuum corrugation feeder with optimized performance for a large variation in sheet sizes is obtained by adjusting the vacuum port area of a vacuum chamber simply by the action of adjusting the paper guides in the paper tray for different sheet sizes.

This invention relates generally to a top vacuum corrugation feeder for an electrophotographic printing machine, and more particularly, to a top vacuum corrugation feeder having movable side guides that can be adjusted for feeding a wide variety of document or copy sheet sizes.
Present high speed xerographic copy reproduction machines produce copies at a rate in excess of several thousand copies per hour, therefore, the need for a sheet feeder to feed cut copy sheets to the machine in a rapid, dependable manner has been recognized to enable full utilization of the reproduction machine's potential copy output. In particular, for many purely duplicating operations, it is desired to feed cut copy sheets at very high speeds where multiple copies are made of an original placed on the copying platen. In addition, for many high speed copying operations, a document handler to feed documents from a stack to a copy platen of the machine in a rapid dependable manner also been reorganized to enable full utilization of the machine's potential copy output. These sheet feeders must operate flawlessly to virtually eliminate the risk of damaging the sheets and generate minimum machine shutdowns due to uncorrectable misfeeds or sheet multifeeds. It is in the initial separation of the individual sheets from the sheet stack where the greatest number of problems occur.
One of the sheet feeders best known for high speed operation is the top vacuum corrugation feeder with front air knife. In this system, a vacuum plenum with a plurality of friction belts arranged to run over the vacuum plenum is placed at the top of a stack of sheets in a supply tray. At the front of the stack, an air knife is used to inject air into the stack to separate the top sheet from the remainder of the stack. In operation, air is injected by the air knife toward the stack to separate the top sheet, the vacuum pulls the separated sheet up and acquires it. Following acquisition, the belt transport drives the sheet forward off the stack of sheets. In this configuration, separation of the next sheet cannot take place until the top sheet has cleared the stack. In this type of feeding system every operation takes place in succession or serially, and therefore, the feeding of subsequent sheets cannot be started until the feeding of the previous sheet has been completed. In addition, in this type of system the air knife may cause the second sheet to vibrate independent of the rest of the stack in a manner referred to as "flutter". When the second sheet is in this situation, if it touches the top sheet, it may tend to creep forwardly slightly with the top sheet. The air knife then may drive the second sheet against the first sheet causing a shingle or double feeding of sheets. Also, some current top and bottom vacuum corrugation feeders utilize a valved vacuum feedhead, e.g., U.S. Pat. Nos. 4,269,406 and 4,451,028. At the appropriate time during the feed cycle the valve is actuated, establishing a flow and hence a negative pressure field over the stack top or bottom if a bottom vacuum corrugation feeder is employed. This field causes the movement of the top sheet(s) to the vacuum feedhead where the sheet is then transported to the take-away rolls. Once the sheet feed edge is under control of the take-away rolls, the vacuum is shut off. The trail edge of this sheet exiting the feedhead area is the criteria for again activating the vacuum valve for the next feeding. A top vacuum corrugation feeder with a valveless vacuum system is shown in U.S. Pat. No. 4,699,369 and all of the heretofore mentioned patents are included herein by reference.
Current customer requirements for middle volume machines include the furnishing of sheet feeders that handle sheets ranging in size from A6 to 12".times.18". If the port area of a vacuum feedhead of a top vacuum corrugation feeder is designed for the A6 size sheets, there may be insufficient flow and pressure to acquire and feed the larger sheets. However, if the air system is designed for the larger sheets, smaller sheets will not cover all of the port openings, allowing air leakage and reducing feeder performance. Therefore, an improved feeder is needed that will reliably feed a wide variety of sheet sizes.

Adjustable top vacuum corrugation feeder


A Heads-Up Display (HUD) system comprises a processor, a power source, and one or more sensors coupled to a frame connector. The processor is configured to receive signals from the one or more sensors and output image data. A display is mounted on a display arm extending from the frame connector. The display is configured to display images based on the image data. A goggles frame is configured to releasably receive the frame connector. The display is located within a field of view of a user wearing the goggles frame when the frame connector is received by the goggles frame.

Any discussion of the prior art throughout the specification should in no way be considered as an admission that such prior art is widely known or forms part of general common knowledge in the field.
In many activities that people participate in, it is desirable or required that they wear head and/or eye protection. By way of non-limiting example, many skiers and snowboarders wear goggles, and many motorcyclists and hockey players wear helmets, which may have visors.
Also, there are systems for providing skiers, snowboarders and others taking part in physical activities with information regarding their performance or status. Some current solutions include handheld GPS devices, performance measurement units, wristwatches, and mobile phones. There also exist such information systems built into goggles or helmets such as those disclosed, for example, in International Applications No. PCT/CA2010/001592 and No. PCT/CA2011/050023, which are hereby incorporated by reference herein.
The inventors have determined a need for improved head-mounted information systems.


According to one embodiment, a magnetic memory device includes a stacked structure including a magnetic layer, and an upper structure provided on the stacked structure, and including a first portion and a second portion surrounding the first portion and formed of material different from that of the first portion.

A magnetic memory device is proposed into which transistors and magnetoresistive effect elements are integrated on a semiconductor substrate. In general, a pattern of the magnetoresistive effect element is formed by performing ion beam etching (IBE) using a hard mask as a mask.
However, if the element is made more minute, there is a risk that the hard mask could not sufficiently satisfactorily function as a mask, and thus a desired magnetoresistive effect element could not be obtained.
Therefore, it is hoped that a magnetic memory device including a hard mask which can sufficiently satisfactorily function as a mark and a method of manufacturing the same will be provided.

Magnetic memory device including upper structure having first portion and second portion surrounding first portion and formed of material different from that of first portion, and method of manufacturing the same


A loader arm assembly is configured to rotate about an axis defined by a pivot pin. The loader arm assembly includes a loader arm having a first end and a second end, the first end having a cavity. The cavity is configured to be aligned with an axis of rotation. The cavity has a cavity perimeter. The loader arm assembly further includes a pivot tube assembly including a pivot tube having an inner bore configured to engage a pivot pin for rotation about the axis. The pivot tube further has an outer perimeter. A portion of the outer perimeter fixedly engages the cavity perimeter. The pivot tube assembly further includes one or more plates extending from the pivot tube in fixed parallel engagement with the loader arm.

A loader vehicle generally includes a wheeled tractor or other engine-driven vehicle. A bucket is attached to one end by two arms. The arms lift and rotate the bucket under power and control from the tractor. In its lowest position, the bucket may be maintained substantially level with the ground for scraping, digging and dozing dirt, gravel, grain or other material. In its highest position, the bucket is several feet off the ground. Rotation of the bucket allows the bucket to roll back, to prevent spillage of contents during transport and to roll forward for dumping. The vehicle includes a hydraulic system for raising, lowering and rotating the bucket. An operator in a cab controls the operation of the loader. A backhoe-loader vehicle includes a bucket at one end and a backhoe at the other end.
The combination of bucket and arms is known as a boom. The two arms are attached to the vehicle chassis at one end and to the bucket at the other end. The connection to the chassis is known as the upper pivot point. At the upper pivot point, the arms rotate about an axis defined by the points of attachment between the arms and the chassis. Hydraulic cylinders are connected between the arm and chassis. Operation of the hydraulic cylinders rotates the arms about the axis, raising and lowering the boom.
The bucket is also attached to the arms by a rotating connection. The bucket rotates about an axis defined by the points of attachment between the bucket and the arms. A hydraulic linkage controls rotation of the bucket. The hydraulic linkages which move the arms and the bucket are under control of the operator.
Normal use of the boom for loader operation puts extreme mechanical stress on the entire boom assembly. Scraping and lifting operations in particular put both compressive and torsional stress on the boom. The upper pivot points, where the arms attach to the vehicle chassis, are particularly affected by torsional stress.
The forces generated by operation of the loader may be sufficient to structurally damage the loader at the upper pivot points. Damage may occur to one or both of the arms of the boom or to the chassis at the point where the arms attach.
Accordingly, there is a need for a reinforced loader arm assembly capable of withstanding the compressive and torsional stresses associated with operation of the loader.


Methods, systems, and computer programs, for estimating think times. One of the methods includes receiving a request to perform a test of one or more computing resources. The test of the one or more computing resources is performed by simulating an interaction of one or more simulated users with the one or more computing resources. Requests are submitted from the simulated user for execution by the one or more computing resources. Respective response times of the one or more computing resources to each of the requests are measured. An estimated think time of the simulated user is computed, wherein the estimated think time is computed based on at least one preceding response time.

This document relates to techniques for estimating think times during testing of computer resources.
To test how computing resources will perform in a production environment, conventional testing systems can submit requests from simulated users for processing by the computing resources that are being tested and measure the response time of the computing resources to the requests. Because each simulated user will generally submit multiple requests during testing, these conventional testing systems also generally employ a think time between each request submitted by a user. The think time is the amount of time between the time that a simulated user receives a response to a request and the time that the simulated user submits another request. Generally, the think time is an estimate of the time that a real user would delay between receiving a response to one request and submitting another request. Some conventional testing systems treat response time and think time as being independent. However, studies have shown that, for some real users, a longer response time to their provided request may result in a longer delay between receiving the response to the request and submitting a subsequent request.

Estimating think times using a measured response time


A vehicle which includes a fuel cell, a receptacle, a lid, and a fixing pin, and which stores a detection of the open state during a period from a time point of a latest end of operation of the vehicle to a time point of input acceptance of a start-up instruction. If a detection of an open state has been stored in a memory at a time point of input acceptance of a start-up instruction, then the vehicle executes a retry operation of temporarily moving the fixing pin of the fixed position to the released position and thereafter moving the fixing pin again to the fixed position during an operating period of the vehicle from the time point of input acceptance of the start-up instruction.

Field
The present invention relates to a fuel cell-equipped vehicle and a control method therefor.
Related Art
JP2011-156896A teaches a fuel cell-equipped vehicle (fuel cell vehicle), which includes a receptacle (charging port) for accepting charging of a fuel from outside of the vehicle, and an openable/closable lid (lid member) for covering the receptacle. JP2004-148980A teaches a lock mechanism for fixing such a lid in a closed state.
With the fuel cell vehicles of JP2011-156896A and JP2004-148980A, there has been a possibility that the fuel cell vehicle may travel while the lid covering the receptacle is not fixed in the closed state due to a positional shift of the lid, a timing shift of the lid fixation operation effected by the lock mechanism, an irregular operation by the user, or the like. When the fuel cell vehicle travels with the lid unfixed to the closed state, the lid may be damaged when the lid having come to an open state during a travel of the fuel cell vehicle hits against an obstacle. Thus, there has been a desire for a technique that can securely prevent the lid covering the receptacle from going to the open state when the fuel cell vehicle is traveling.

Fuel cell-equipped vehicle and control method therefor


A filter body of a common mode noise filter includes: a non-magnetic body; a first magnetic body and a second magnetic body sandwiching the non-magnetic body; and a first coil conductor and a second coil conductor of planar shape which are embedded in the non-magnetic body and positioned on the first magnetic body side and second magnetic body side in the non-magnetic body in a manner facing each other in a non-contact state; and also has a non-magnetic first protective part and second protective part which are made of a non-magnetic material whose strength is higher than the first magnetic body and second magnetic body and which are positioned on the outermost side of the filter body in a manner sandwiching the first magnetic body and second magnetic body.

A common mode noise filter generally has a structure whereby a filter body, constituted by two magnetic bodies sandwiching a non-magnetic body in which two coils are embedded, has two pairs of external terminals provided on it which are each electrically continuous with each of the coils (refer to Patent Literature 1).
Below is an example where the non-magnetic body is made of borosilicate glass and each magnetic body is made of Ni—Zn—Cn ferrite. Since the strength (mechanical strength) of each magnetic body is lower than the strength of the non-magnetic body, when external force is applied to the common mode noise filter as the common mode noise filter is installed on a circuit board, etc., transferred, or the like, the two magnetic bodies positioned on the outermost side of the filter body, especially the ridgelines of each magnetic body, may be chipped. This chipping can lead to volume decrease of each magnetic body and consequently cause the impedance characteristics and other filter characteristics to deteriorate as a result of volume decrease caused by the chipping.


A reflective type liquid crystal display which has, between a pair of transparent substrates with electrodes thereon, a nematic liquid crystal composition which exhibits a cholesteric phase at room temperature. The liquid crystal composition contains a nematic liquid crystal mixture containing a liquid crystalline difluorostilbene compound, and a chiral agent. The concentration of the liquid crystalline difluorostilbene compound in the liquid crystal composition is preferably in a range from 5 wt % to 60 wt %.

This application is based on application No. 11-358419 filed in Japan, the contents of which are incorporated by reference.
1. Field of the Invention
The present invention relates to a liquid crystal composition and a liquid crystal light modulating device such as a liquid crystal display which uses the liquid crystal composition.
2. Description of Related Art
In recent years, various kinds of reflective type liquid crystal displays which use chiral nematic liquid crystal have been developed. The chiral nematic liquid crystal is prepared by adding a chiral agent to nematic liquid crystal so as to exhibit a cholesteric phase at room temperature. Such a liquid crystal display makes a display by switching the liquid crystal between a planar state (colored state) and a focal-conic state (transparent state) when a pulse signal of a specified voltage is applied to the liquid crystal. The liquid crystal display can be so structured as to keep the colored/transparent states even after stoppage of the application of voltage.
This kind of liquid crystal is expected to be used in a different field from liquid crystal for displaying motion pictures. This kind of liquid crystal is typically used as a substitution for paper on which an image is printed. For example, the liquid crystal can be used for electronic blackboards, bulletin boards, electronic books, decorative panels, etc.
This kind of liquid crystal is desired to have the following characteristics: being driven by a low voltage; displaying an image at high definition with high contrast; having a wide operating temperature range; responding to a low temperature, etc. The liquid crystal is especially desired to be driven by a low voltage, to have a high response speed and to display an image with high contrast. There is, however, a well-known fact that when a chiral agent is added to nematic liquid crystal, the driving voltage becomes higher, and the response speed is lowered. Also, when some measures are taken to improve the liquid crystal in one or some of the above desirable characteristics, the liquid crystal is likely to degrade in other characteristics.
An object of the present invention is to provide a liquid crystal composition and a liquid crystal light modulating device which can be driven by a low voltage, have a high response speed and displays an image with high contrast.
In order to attain the object, a liquid crystal composition according to the present invention comprises: a nematic liquid crystal mixture which contains a liquid crystalline difluorostilbene compound; and a chiral agent. The liquid crystal composition exhibits a cholesteric phase at room temperature.
When a plurality of voltages of mutually different strengths are applied to such a liquid crystal composition which exhibits a cholesteric phase at room temperature, the liquid crystal composition switches between a state to selectively reflect light of a specified wavelength (selective reflection state) and a state to transmit incident light (transparent state).
Liquid crystalline difluorostilbene compounds generally have low viscosity and high anisotropy of refractive index. Therefore, by containing such a liquid crystalline difluorostilbene compound in such a liquid crystal composition, the viscosity of the liquid crystal composition becomes lower, the response speed of the liquid crystal composition becomes higher, and the driving voltage to drive the liquid crystal composition becomes lower. Also, the contrast which is the ratio of the Y value in the selective reflection state to the Y value in the transparent state becomes higher.
Liquid crystalline difluorostilbene compounds represented by the following formula are usable:
R1: alkyl group with 1 to 10 carbon atoms or alkenyl group with 2 to 20 carbon atoms
A1: single bond or 1,4-cyclohexylene group
X1: xe2x80x94F, xe2x80x94Cl or xe2x80x94CN
Q1: xe2x80x94F or xe2x80x94H
Z1: xe2x80x94F or xe2x80x94H
The concentration of the liquid crystalline difluorostilbene compound in the liquid crystal composition is preferably in a range from 5 wt % to 60 wt %.
The liquid crystal composition according to the present invention may comprise other liquid crystalline compounds. For example, various kinds of liquid crystalline compounds generally used for nematic liquid crystal, such as liquid crystalline phenylcyclohexane compounds, liquid crystalline tolane compounds, liquid crystalline ester compounds, liquid crystalline pyrimidine compounds, liquid crystalline polycyclic compounds, nonpolar liquid crystalline compounds, etc., may be contained.
Such liquid crystalline difluorostilbene compounds can be produced by a conventional method. For example, the method disclosed by Japanese Patent Laid Open Publication No. 11-49707 can be adopted.
The concentration of the chiral agent in the liquid crystal composition is preferably in a range from 10 wt % to 45 wt %. By setting the concentration of the chiral agent in this range, deposition of crystal can be prevented, and the wavelength of light to be reflected by the liquid crystal composition can be set within a desired wavelength range.
The liquid crystal composition may further comprise a coloring agent. By adding a coloring agent, the color purity of the liquid crystal composition can be adjusted.
A liquid crystal light modulating device according to the present invention comprises: a pair of substrates, at least one of which is transparent; and a liquid crystal layer which is sandwiched between the substrates, the liquid crystal layer comprising the above-described liquid crystal composition. The liquid crystal light modulating device requires a low driving voltage, has a high response speed and can display an image with high contrast.
The liquid crystal layer may have a memory effect. In this case, even after stopping application of a voltage to the light modulating device, the light modulating device can keep displaying an image. Therefore, the liquid crystal modulating device can be used, for example, as an energy-saving display device.
On the substrates, electrodes are formed, and further, an insulating film which function as an alignment controlling layer and/or a color filter may be provided thereon. The insulating film stabilizes the operation of the liquid crystal light modulating device and improves the light modulation performance.
Between the substrates, polymer nodules may be provided. The polymer nodules keep the gap between the substrates more accurately and contributes to achievement of desired light modulation performance.
The substrate which is at a light incidence side may have an ultraviolet-ray absorbing characteristic or an ultraviolet-ray absorbing layer. Also, the other substrate which is opposite the light incidence side may have a light absorbing characteristic or a light absorbing layer.

Liquid crystal composition and liquid crystal light modulating device using the liquid crystal composition