The invention provides isolated polypeptide and nucleic acid sequences derived from Candida albicans that are useful in diagnosis and therapy of pathological conditions; antibodies against the polypeptides; and methods for the production of the polypeptides. The invention also provides methods for the detection, prevention and treatment of pathological conditions resulting from fungal infection.

The invention relates to isolated nucleic acids and polypeptides derived from Candida albicans that are useful as molecular targets for diagnostics, prophylaxis and treatment of pathological conditions, as well as materials and methods for the diagnosis, prevention, and amelioration of pathological conditions resulting from fungal infection.
Incorporated herein by reference in its entirety is a Sequence Listing comprising SEQ ID No. 1 to SEQ ID NO:28208. The Sequence Listing is contained on a CD-ROM, three copies of which are filed, the Sequence Listing being in a computer-readable ASCII file named xe2x80x9ccand09.2001.txtxe2x80x9d, created on Sep. 14, 2001 and of 38,660 bytes in size, in IBM-PC Windows(copyright)NT v4.0 format.
Candida albicans is a dimorphic fungus which has both a yeast-like growth habit and a filamentous form consisting of both hyphae and pseudohypae. The fungus is a member of the normal surface flora of most individuals. Although no sexual state has been described for C. albicans, the genome is diploid in most strains (Whelan, W L et al. (1980) Mol. Gen. Genet. 180: 107-113; Whelan, W L and Magee, P T (1981) J. Bacteriol. 145: 896-903; Poulter, R. (1982) J. Bacteriol. 152: 969-975) and rearranges relatively frequently (Rustchenko-Bulgac E P, et al (1990) J Bacteriol. 172: 1276-1283; Barton, R C and Scherer, S (1994)J. Bacteriol . 176: 756-763). In addition, one non-universal decoding is known in which a leucine codon (CUG) is translated as a serine (Leuker et al. (1994), Mol. Gen. Genet. 245: 212-217; Santos et al., (1993) EMBO Journal 12:607-616). This creates difficulties in the application of the powerful genetic and molecular methods used in Saccharomyces and Schizosaccharomyces.
C. albicans exists as part of the normal microbial flora in humans, but can produce opportunistic infections ranging from topical infections such as oral thrush to life-threatening disseminated mycoses (Ampel, N M (1996) Emerg. Infect. Dis. 2: 109-116). Candida is a major cause of nosocomial infections and was found to account for more than 75% of all fungal nosocomial infections reported by NNIS (National Nosocomial Infections Surveillance) hospitals from 1980-1990 in which fungi alone accounted for 7.9% of all nosocomial infections (Beck-Sagu, C M and Jarvis, W R (1993) J. Infect. Dis. 167: 1247-1251). Although the source of Candida in infections is frequently traced to endogenous sources on the patient, it has also been traced to exogenous sources in the hospital environment including contaminated solutions and equipment (Shetertz, R J et al. (1992) J. Pediatr. 120: 455-461; Weems, J J et al. (1987) J. Clin. Microbiol. 1925: 1029-1032), and health care workers (Hunter, P R et al (1990) J. Med Vet Mycol. 28: 317-325; Burnie, J P (1986) J. Hosp. Infect. 8: 1-4; Doebbeling, B N et al. (1991) J. Clin. Microbiol. 29: 1268-1270). Numerous investigations into the molecular basis of pathogenicity have been made implicating the hyphal form (Lo, H J et al. (1997) Cell 90:939-949), surface molecules including adhesins (Fukazawa Y and Kagaya K (1997)J Med Vet Mycol 35:87-99), and ATP-binding cassette-containing multi-drug resistance proteins (Prasad, R et al.(1995) Curr. Genet. 27: 320-329).
The antimicrobials currently in use against Candida are generally of three types: azoles, such as iluconazole, itraconazole, and clotrimazole; polyenes, such as amphotericin B and nystatin; and 5-fluorocytosine. However, invasive infections are treated primarily with fluconazole, amphotericin B, and 5-fluorocytosine, although the latter two compounds have significant toxic side effects. The development of resistance to iluconazole by C. albicans has been noted by a number of researchers (Redding, S (1994) Clin. Infect. Dis. 18: 339-346; Sargeorzan, J A (1994) Am. J. Med. 97: 339-346; Revankar, S G et al. (1996) J. Infect. Dis. 174: 821-827; Marr, K A et al. (1997) Clin. Infect. Dis 25: 908-910). Relatively short treatments seem to result in few if any resistant isolates, but extended treatments including prophylactic treatments such as are required among immunocompromised and AIDS patients, result in the appearance of fluconazole-resistant strains (Johnson, E M (1995) J. Antimicrob. Chemother. 35: 103-114). Development of fluconazole-resistance has been observed to be associated with the development of amphotericin-resistance (Vazquez, J A (1996) Antimicrob. Agents Chemother. 40: 2511-2516; Nolte, F S et al. (1997) Antimicrob. Agents Chemother. 41: 196-199; White, T C (1997) ASM News 63: 427-433) consistent with the action of both drugs on ergosterol in the membrane.
The difficulty in diagnosing C. albicans infections, the limited spectrum of current therapeutic drugs and the development of drug resistant strains of C. albicans provide the rationale for the identification of targets for more rapid and effective methods of identification, prevention, and treatment of candidiasis. The elucidation of the genome of C. albicans would enhance the understanding of how C. albicans, as well as other fungi, causes invasive disease and how best to combat fungal infection.
The present invention fulfills the need for diagnostic tools and therapeutics by providing fungal-specific compositions and methods for detecting, treating, and preventing fungal infection, in particular C. albicans infection. They also have use as biocontrol agents for plants.
The present invention encompasses isolated nucleic acids and polypeptides derived from C. albicans that are useful as reagents for diagnosis of fungal disease, components of effective antifungal vaccines, and/or as targets for antifungal drugs including anti-C. albicans drugs. They can also be used to detect the presence of C. albicans and other Candida species in a sample; and in screening compounds for the ability to interfere with the C. albicans life cycle or to inhibit C. albicans infection.
More specifically, this invention features compositions of nucleic acids corresponding to entire coding sequences of C. albicans proteins, including surface or secreted proteins or parts thereof, nucleic acids capable of binding mRNA from C. albicans proteins to block protein translation, and methods for producing C. albicans proteins or parts thereof using peptide synthesis and recombinant DNA techniques. This invention also features antibodies and nucleic acids useful as probes to detect C. albicans infection. In addition, vaccine compositions and methods for the protection or treatment of infection by C. albicans are within the scope of this invention.
The nucleotide sequences provided in SEQ ID NO: 1-SEQ ID NO: 14103, a fragment thereof, or a nucleotide sequence at least about 99.5% identical to a sequence contained within SEQ ID NO: 1-SEQ ID NO: 14103 may be xe2x80x9cprovidedxe2x80x9d in a variety of medias to facilitate use thereof. As used herein, xe2x80x9cprovidedxe2x80x9d refers to a manufacture, other than an isolated nucleic acid molecule, which contains a nucleotide sequence of the present invention, i.e., the nucleotide sequence provided in SEQ ID NO: 1-SEQ ID NO: 14103, a fragment thereof, or a nucleotide sequence at least about 99.5% identical to a sequence contained within SEQ ID NO: 1-SEQ ID NO: 14103. Uses for and methods for providing nucleotide sequences in a variety of media is well known in the art (see e.g., EPO Publication No. EP 0 756 006).
In one application of this embodiment, a nucleotide sequence of the present invention can be recorded on computer readable media. As used herein, xe2x80x9ccomputer readable mediaxe2x80x9d refers to any media which can be read and accessed directly by a computer. Such media include, but are not limited to: magnetic storage media, such as floppy discs, hard disc storage media, and magnetic tape; optical storage media such as CD-ROM; electrical storage media such as RAM and ROM; and hybrids of these categories such as magnetic/optical storage media. A person skilled in the art can readily appreciate how any of the presently known computer readable media can be used to create a manufacture comprising computer readable media having recorded thereon a nucleotide sequence of the present invention.
As used herein, xe2x80x9crecordedxe2x80x9d refers to a process for storing information on computer readable media. A person skilled in the art can readily adopt any of the presently known methods for recording information on computer readable media to generate manufactures comprising the nucleotide sequence information of the present invention.
A variety of data storage structures are available to a person skilled in the art for creating a computer readable media having recorded thereon a nucleotide sequence of the present invention. The choice of the data storage structure will generally be based on the means chosen to access the stored information. In addition, a variety of data processor programs and formats can be used to store the nucleotide sequence information of the present invention on computer readable media. The sequence information can be represented in a word processing text file, formatted in commercially-available software such as WordPerfect and Microsoft Word, or represented in the form of an ASCII file, stored in a database application, such as DB2, Sybase, Oracle, or the like. A person skilled in the art can readily adapt any number of data processor structuring formats (e.g. text file or database) in order to obtain computer readable media having recorded thereon the nucleotide sequence information of the present invention.
By providing the nucleotide sequence of SEQ ID NO: 1-SEQ ID NO: 14103, a fragment thereof, or a nucleotide sequence at least about 99.5% identical to SEQ ID NO: 1-SEQ ID NO: 14103 in computer readable form, a person skilled in the art can routinely access the coding sequence information for a variety of purposes. Computer software is publicly available which allows a person skilled in the art to access sequence information provided in a computer readable media. Examples of such computer software include programs of the xe2x80x9cStaden Packagexe2x80x9d, xe2x80x9cDNA Starxe2x80x9d, xe2x80x9cMacVectorxe2x80x9d, GCG xe2x80x9cWisconsin Packagexe2x80x9d (Genetics Computer Group, Madison, Wis.) and xe2x80x9cNCBI Toolboxxe2x80x9d (National Center For Biotechnology Information). Suitable programs are described, for example, in Martin J. Bishop, ed., Guide to Human Genome Computing, 2d Edition, Academic Press, San Diego, Calif. (1998); and Leonard F. Peruski, Jr., and Anne Harwood Peruski, The Internet and the New Biology: Tools for Genomic and Molecular Research, American Society for Microbiology, Washington, D.C. (1997).
Computer algorithms enable the identification of C. albicans open reading frames (ORFs) within SEQ ID NO: 1-SEQ ID NO: 14103 which contain homology to ORFs or proteins from other organisms. Examples of such similarity-search algorithms include the BLAST [Altschul et al., J. Mol. Biol. 215:403-410 (1990)] and Smith-Waterman [Smith and Waterman (1981) Advances in Applied Mathematics, 2:482-489] search algorithms. Suitable search algorithms are described, for example, in Martin J. Bishop, ed., Guide to Human Genome Computing, 2d Edition, Academic Press, San Diego, Calif. (1998); and Leonard F. Peruski, Jr., and Anne Harwood Peruski, The Internet and the New Biology: Tools for Genomic and Molecular Research, American Society for Microbiology, Washington, D.C. (1997). Such algorithms are utilized on computer systems as exemplified below. The ORFs so identified represent protein encoding fragments within the C. albicans genome and are useful in producing commercially important proteins such as enzymes used in fermentation reactions and in the production of commercially useful metabolites.
The present invention further provides systems, particularly computer-based systems, which contain the sequence information described herein. Such systems are designed to identify commercially important fragments of the C. albicans genome. As used herein, xe2x80x9ca computer-based systemxe2x80x9d refers to the hardware means, software means, and data storage means used to analyze the nucleotide sequence information of the present invention. The minimum hardware means of the computer-based systems of the present invention comprises a central processing unit (CPU), input means, output means, and data storage means. A person skilled in the art can readily appreciate that any one of the currently available computer-based systems is suitable for use in the present invention. The computer-based systems of the present invention comprise a data storage means having stored therein a nucleotide sequence of the present invention and the necessary hardware means and software means for supporting and implementing a search means. As used herein, xe2x80x9cdata storage meansxe2x80x9d refers to memory which can store nucleotide sequence information of the present invention, or a memory access means which can access manufactures having recorded thereon the nucleotide sequence information of the present invention.
As used herein, xe2x80x9csearch meansxe2x80x9d refers to one or more programs which are implemented on the computer-based system to compare a target sequence or target structural motif with the sequence information stored within the data storage means. Search means are used to identify fragments or regions of the C. albicans genome which are similar to, or xe2x80x9cmatchxe2x80x9d, a particular target sequence or target motif. A variety of known algorithms are known in the art and have been disclosed publicly, and a variety of commercially available software for conducting homology-based similarity searches are available and can be used in the computer-based systems of the present invention. Examples of such software include, but are not limited to, FASTA (GCG Wisconsin Package), Bic_SW (Compugen Bioccelerator), BLASTN2, BLASTP2, BLASTX2 (NCBI) and Motifs (GCG). Suitable software programs are described, for example, in Martin J. Bishop, ed., Guide to Human Genome Computing, 2d Edition, Academic Press, San Diego, Calif. (1998); and Leonard F. Peruski, Jr., and Anne Harwood Peruski, The Internet and the New Biology: Tools for Genomic and Molecular Research, American Society for Microbiology, Washington, D.C. (1997). A person skilled in the art will readily recognize that any one of the available algorithms or implementing software packages for conducting homology searches can be adapted for use in the present computer-based systems.
As used herein, a xe2x80x9ctarget sequencexe2x80x9d can be any DNA or amino acid sequence of six or more nucleotides or two or more amino acids. A person skilled in the art can readily recognize that the longer a target sequence is, the less likely a target sequence will be present as a random occurrence in the database. The most preferred sequence length of a target sequence is from about 10 to 100 amino acids or from about 30 to 300 nucleotide residues. However, it is well recognized that many genes are longer than 500 amino acids, or 1.5 kb in length, and that commercially important fragments of the C. albicans genome, such as sequence fragments involved in gene expression and protein processing, will often be shorter than 30 nucleotides.
As used herein, xe2x80x9ca target structural motif,xe2x80x9d or xe2x80x9ctarget motif,xe2x80x9d refers to any rationally selected sequence or combination of sequences in which the sequence(s) are chosen based on a specific functional domain or three-dimensional configuration which is formed upon the folding of the target polypeptide. There is a variety of target motifs known in the art. Protein target motifs include, but are not limited to, enzymatic active sites, membrane-spanning regions, and signal sequences. Nucleic acid target motifs include, but are not limited to, promoter sequences, hairpin structures and inducible expression elements (protein binding sequences).
A variety of structural formats for the input and output means can be used to input and output the information in the computer-based systems of the present invention. A preferred format for an output means ranks fragments of the C. albicans genome possessing varying degrees of homology to the target sequence or target motif. Such presentation provides a person skilled in the art with a ranking of sequences which contain various amounts of the target sequence or target motif and identifies the degree of homology contained in the identified fragment.
A variety of comparing means can be used to compare a target sequence or target motif with the data storage means to identify sequence fragments of the C. albicans genome. In the present examples, implementing software which implement the BLASTP2 and bic_SW algorithms (Altschul et al., J Mol. Biol. 215:403-410 (1990); Compugen Biocellerator) was used to identify open reading frames within the C. albicans genome. A person skilled in the art can readily recognize that any one of the publicly available homology search programs can be used as the search means for the computer-based systems of the present invention. Suitable programs are described, for example, in Martin J. Bishop, ed., Guide to Human Genome Computing, 2d Edition, Academic Press, San Diego, Calif. (1998); and Leonard F. Peruski, Jr., and Anne Harwood Peruski, The Internet and the New Biology: Tools for Genomic and Molecular Research, American Society for Microbiology, Washington, D.C. (1997).
The invention features C. albicans polypeptides, preferably a substantially pure preparation of an C. albicans polypeptide, or a recombinant C. albicans polypeptide. In preferred embodiments: the polypeptide has biological activity; the polypeptide has an amino acid sequence at least about 60%, 70%, 80%, 90%, 95%, 98%, or 99% identical to an amino acid sequence of the invention contained in the Sequence Listing, preferably it has about 65% sequence identity with an amino acid sequence of the invention contained in the Sequence Listing, and most preferably it has about 92% to about 99% sequence identity with an amino acid sequence of the invention contained in the Sequence Listing; the polypeptide has an amino acid sequence essentially the same as an amino acid sequence of the invention contained in the Sequence Listing; the polypeptide is at least about 5, 10, 20, 50, 100, or 150 amino acid residues in length; the polypeptide includes at least about 5, preferably at least about 10, more preferably at least about 20, more preferably at least about 50, 100, or 150 contiguous amino acid residues of the invention contained in the Sequence Listing. In yet another preferred embodiment, the amino acid sequence which differs in sequence identity by about 7% to about 8% from the C. albicans amino acid sequences of the invention contained in the Sequence Listing is also encompassed by the invention.
In preferred embodiments: the C. albicans polypeptide is encoded by a nucleic acid of the invention contained in the Sequence Listing, or by a nucleic acid having at least about 60%, 70%, 80%, 90%, 95%, 98%, or 99% homology with a nucleic acid of the invention contained in the Sequence Listing.
In a preferred embodiment, the subject C. albicans polypeptide differs in amino acid sequence at about 1, 2, 3, 5, 10 or more residues from a sequence of the invention contained in the Sequence Listing. The differences, however, are such that the C. albicans polypeptide exhibits an C. albicans biological activity, e.g., the C. albicans polypeptide retains a biological activity of a naturally occurring C. albicans enzyme.
In preferred embodiments, the polypeptide includes all or a fragment of an amino acid sequence of the invention contained in the Sequence Listing; fused, in reading frame, to additional amino acid residues, preferably to residues encoded by genomic DNA 5xe2x80x2 or 3xe2x80x2 to the genomic DNA which encodes a sequence of the invention contained in the Sequence Listing.
In yet other preferred embodiments, the C. albicans polypeptide is a recombinant fusion protein having a first C. albicans polypeptide portion and a second polypeptide portion, e.g., a second polypeptide portion having an amino acid sequence unrelated to C. albicans. The second polypeptide portion can be, e.g., any of glutathione-S-transferase, a DNA binding domain, or a polymerase activating domain. In preferred embodiment the fusion protein can be used in a two-hybrid assay.
Polypeptides of the invention include those which arise as a result of alternative transcription events, alternative RNA splicing events, and alternative translational and postranslational events.
In a preferred embodiment, the encoded C. albicans polypeptide differs (e.g., by amino acid substitution, addition or deletion of at least one amino acid residue) in amino acid sequence at about 1, 2, 3, 5, 10 or more residues, from a sequence of the invention contained in the Sequence Listing. The differences, however, are such that: the C. albicans encoded polypeptide exhibits a C. albicans biological activity, e.g., the encoded C. albicans enzyme retains a biological activity of a naturally occurring C. albicans.
In preferred embodiments, the encoded polypeptide includes all or a fragment of an amino acid sequence of the invention contained in the Sequence Listing; fused, in reading frame, to additional amino acid residues, preferably to residues encoded by genomic DNA 5xe2x80x2 or 3xe2x80x2 to the genomic DNA which encodes a sequence of the invention contained in the Sequence Listing.
The C. albicans strain from which the nucleotide sequences have been sequenced is strain SC5314, a clinical isolate which was originally obtained from a patient with disseminated candidiasis.
Included in the invention are: allelic variations; natural mutants; induced mutants; proteins encoded by DNA that hybridize under high or low stringency conditions to a nucleic acid which encodes a polypeptide of the invention contained in the Sequence Listing (for definitions of high and low stringency see Current Protocols in Molecular Biology, John Wiley and Sons, New York, 1989, 6.3.1-6.3.6, hereby incorporated by reference); and, polypeptides specifically bound by antisera to C. albicans polypeptides, especially by antisera to an active site or binding domain of C. albicans polypeptide. The invention also includes fragments, preferably biologically active fragments. These and other polypeptides are also referred to herein as C. albicans polypeptide analogs or variants.
The invention further provides nucleic acids, e.g., RNA or DNA, encoding a polypeptide of the invention. This includes double stranded nucleic acids as well as coding and antisense single strands.
In preferred embodiments, the subject C. albicans nucleic acid will include a transcriptional regulatory sequence, e.g. at least one of a transcriptional promoter or transcriptional enhancer sequence, operably linked to the C. albicans gene sequence, e.g., to render the C. albicans gene sequence suitable for expression in a recombinant host cell.
In yet a further preferred embodiment, the nucleic acid which encodes an C. albicans polypeptide of the invention, hybridizes under stringent conditions to a nucleic acid probe corresponding to at least about 8 consecutive nucleotides of the invention contained in the Sequence Listing; more preferably to at least about 12 consecutive nucleotides of the invention contained in the Sequence Listing; more preferably to at least about 20 consecutive nucleotides of the invention contained in the Sequence Listing; more preferably to at least about 40 consecutive nucleotides of the invention contained in the Sequence Listing.
In another aspect, the invention provides a substantially pure nucleic acid having a nucleotide sequence which encodes an C. albicans polypeptide. In preferred embodiments: the encoded polypeptide has biological activity; the encoded polypeptide has an amino acid sequence at least about 60%, 70%, 80%, 90%, 95%, 98%, or 99% homologous to an amino acid sequence of the invention contained in the Sequence Listing; the encoded polypeptide has an amino acid sequence essentially the same as an amino acid sequence of the invention contained in the Sequence Listing; the encoded polypeptide is at least about 5, 10, 20, 50, 100, or 150 amino acids in length; the encoded polypeptide comprises at least about 5, preferably at least about 10, more preferably at least about 20, more preferably at least about 50, 100, or 150 contiguous amino acids of the invention contained in the Sequence Listing.
In another aspect, the invention encompasses: a vector including a nucleic acid which encodes an C. albicans polypeptide or an C. albicans polypeptide variant as described herein; a host cell transfected with the vector; and a method of producing a recombinant C. albicans polypeptide or C. albicans polypeptide variant; including culturing the cell, e.g., in a cell culture medium, and isolating an C. albicans or C. albicans polypeptide variant, e.g., from the cell or from the cell culture medium.
One embodiment of the invention is directed to substantially isolated nucleic acids. Nucleic acids of the invention include sequences comprising at least about 8 nucleotides in length, more preferably at least about 12 nucleotides in length, even more preferably at least about 15-20 nucleotides in length, that correspond to a subsequence of any one of SEQ ID NO: 1-SEQ ID NO: 14103 or complements thereof. Alternatively, the nucleic acids comprise sequences contained within any ORF (open reading frame), including a complete protein-coding sequence, of which any of SEQ ID NO: 1-SEQ ID NO: 14103 forms a part. The invention encompasses sequence-conservative variants and function-conservative variants of these sequences. The nucleic acids may be DNA, RNA, DNA/RNA duplexes, protein-nucleic acid (PNA), or derivatives thereof.
In another aspect, the invention features, a purified recombinant nucleic acid having at least about 50%, 60%, 70%, 80%, 90%, 95%, 98%, or 99% homology with a sequence of the invention contained in the Sequence Listing.
The invention also encompasses recombinant DNA (including DNA cloning and expression vectors) comprising these C. albicans-derived sequences; host cells comprising such DNA, including fungal, bacterial, yeast, plant, insect, and mammalian host cells; and methods for producing expression products comprising RNA and polypeptides encoded by the C. albicans sequences. These methods are carried out by incubating a host cell comprising a C. albicans-derived nucleic acid sequence under conditions in which the sequence is expressed. The host cell may be native or recombinant. The polypeptides can be obtained by (a) harvesting the incubated cells to produce a cell fraction and a medium fraction; and (b) recovering the C. albicans polypeptide from the cell fraction, the medium fraction, or both. The polypeptides can also be made by in vitro translation.
In another aspect, the invention features nucleic acids capable of binding mRNA of C. albicans. Such nucleic acid is capable of acting as antisense nucleic acid to control the translation of mRNA of C. albicans. A further aspect features a nucleic acid which is capable of binding specifically to a C. albicans nucleic acid. These nucleic acids are also referred to herein as complements and have utility as probes and as capture reagents.
In another aspect, the invention features an expression system comprising an open reading frame corresponding to C. albicans nucleic acid. The nucleic acid further comprises a control sequence compatible with an intended host. The expression system is useful for making polypeptides corresponding to C. albicans nucleic acid.
In another aspect, the invention encompasses: a vector including a nucleic acid which encodes a C. albicans polypeptide or a C. albicans polypeptide variant as described herein; a host cell transfected with the vector; and a method of producing a recombinant C. albicans polypeptide or C. albicans polypeptide variant; including culturing the cell, e.g., in a cell culture medium, and isolating the C. albicans or C. albicans polypeptide variant, e.g., from the cell or from the cell culture medium.
In yet another embodiment of the invention encompasses reagents for detecting fungal infection, including C. albicans infection, which comprise at least one C. albicans-derived nucleic acid defined by any one of SEQ ID NO: 1-SEQ ID NO: 14103, or sequence-conservative or function-conservative variants thereof. Alternatively, the diagnostic reagents comprise polypeptide sequences that are contained within any open reading frames (ORFs), including complete protein-coding sequences, contained within any of SEQ ID NO: 1-SEQ ID NO: 14103, or polypeptide sequences contained within any of SEQ ID NO: 14104-SEQ ID NO: 28206, or polypeptides of which any of the above sequences forms a part, or antibodies directed against any of the above peptide sequences or function-conservative variants and/or fragments thereof.
The invention further provides antibodies, preferably monoclonal antibodies, which specifically bind to the polypeptides of the invention. Methods are also provided for producing antibodies in a host animal. The methods of the invention comprise immunizing an animal with at least one C. albicans-derived immunogenic component, wherein the immunogenic component comprises one or more of the polypeptides encoded by any one of SEQ ID NO: 1-SEQ ID NO: 14103 or sequence-conservative or function-conservative variants thereof; or polypeptides that are contained within any ORFs, including complete protein-coding sequences, of which any of SEQ ID NO: 1-SEQ ID NO: 14103 forms a part; or polypeptide sequences contained within any of SEQ ID NO: 14104-SEQ ID NO: 28206; or polypeptides of which any of SEQ ID NO: 14104-SEQ ID NO: 28206 forms a part. Host animals include any warm blooded animal, including without limitation mammals and birds. Such antibodies have utility as reagents for immunoassays to evaluate the abundance and distribution of C. albicans-specific antigens.
In yet another aspect, the invention provides diagnostic methods for detecting C. albicans antigenic components or anti-C. albicans antibodies in a sample. C. albicans antigenic components are detected by a process comprising: (i) contacting a sample suspected to contain a fungal antigenic component with a fungal-specific antibody, under conditions in which a stable antigen-antibody complex can form between the antibody and fungal antigenic components in the sample; and (ii) detecting any antigen-antibody complex formed in step (i), wherein detection of an antigen-antibody complex indicates the presence of at least one fungal antigenic component in the sample. In different embodiments of this method, the antibodies used are directed against a sequence encoded by any of SEQ ID NO: 1-SEQ ID NO: 14103 or sequence-conservative or function-conservative variants thereof, or against a polypeptide sequence contained in any of SEQ ID NO: 14104-SEQ ID NO: 28206 or function-conservative variants thereof.
In yet another aspect, the invention provides a method for detecting antifungal-specific antibodies in a sample, which comprises: (i) contacting a sample suspected to contain antifungal-specific antibodies with a C. albicans antigenic component, under conditions in which a stable antigen-antibody complex can form between the C. albicans antigenic component and antifungal antibodies in the sample; and (ii) detecting any antigen-antibody complex formed in step (i), wherein detection of an antigen-antibody complex indicates the presence of antifungal antibodies in the sample. In different embodiments of this method, the antigenic component is encoded by a sequence contained in any of SEQ ID NO: 1-SEQ ID NO: 14103 or sequence-conservative and function-conservative variants thereof, or is a polypeptide sequence contained in any of SEQ ID NO: 14104-SEQ ID NO: 28206 or function-conservative variants thereof.
In another aspect, the invention features a method of generating vaccines for immunizing an individual against C. albicans. The method includes: immunizing a subject with a C. albicans polypeptide, e.g., a surface or secreted polypeptide, or a combination of such peptides or active portion(s) thereof, and a pharmaceutically acceptable carrier. Such vaccines have therapeutic and prophylactic utilities.
In another aspect, the invention features a method of evaluating a compound, e.g. a polypeptide, e.g., a fragment of a host cell polypeptide, for the ability to bind a C. albicans polypeptide. The method includes: contacting the candidate compound with a C. albicans polypeptide and determining if the compound binds or otherwise interacts with an C. albicans polypeptide. Compounds which bind C. albicans are candidates as activators or inhibitors of the fungal life cycle. These assays can be performed in vitro or in vivo.
In another aspect, the invention features a method of evaluating a compound, e.g. a polypeptide, e.g., a fragment of a host cell polypeptide, for the ability to bind an C. albicans nucleic acid, e.g., DNA or RNA. The method includes: contacting the candidate compound with a C. albicans nucleic acid and determining if the compound binds or otherwise interacts with a C. albicans polypeptide. Compounds which bind C. albicans are candidates as activators or inhibitors of the fungal life cycle. These assays can be performed in vitro or in vivo.
A particularly preferred embodiment of the invention is directed to a method of screening test compounds for anti-fungal activity, which method comprises: selecting as a target a fungal specific sequence, which sequence is essential to the viability of a fungal species; contacting a test compound with said target sequence; and selecting those test compounds which bind to said target sequence as potential anti-fungal candidates. In one embodiment, the target sequence selected is specific to a single species, or even a single strain, i.e., the C. albicans strain SC5314. In a second embodiment, the target sequence is common to at least two species of fungi. In a third embodiment, the target sequence is common to a family of fungi. The target sequence may be a nucleic acid sequence or a polypeptide sequence. Methods employing sequences common to more than one species of microorganism may be used to screen candidates for broad spectrum anti-fungal activity.
The invention also provides methods for preventing or treating disease caused by certain fungi, including C. albicans, which are carried out by administering to an animal in need of such treatment, in particular a warm-blooded vertebrate, including but not limited to birds and mammals, a compound that specifically inhibits or interferes with the function of a fungal polypeptide or nucleic acid. In a particularly preferred embodiment, the mammal to be treated is human.

Nucleic acid sequences relating to Candida albicans for diagnostics and therapeutics


A solar generator apparatus, which has suspending supports and is mounted on a fixed structure, includes a solar generator module, a middle column, three side columns and three elastic members. The solar generator module converts light into electricity. The middle column for rotatably supporting the solar generator module has a first end mounted on the fixed structure, and a second end pivotally connected to a middle portion of a bottom of the solar generator module. First ends of the three side columns are mounted on the fixed structure. The three elastic members for assisting in supporting the solar generator module respectively connect second ends of the three side columns to the solar generator module.

1. Field of the Invention
The invention relates in general to a solar generator apparatus with suspending supports, and more particularly to a solar generator apparatus using a middle column and elastic members to support a solar generator module.
2. Related Art
Usually, a solar generator system is mounted on a building or at a fixed manner, and cannot be adjusted according to the azimuth angle of the sun, so that the received availability of the solar energy is limited. Alternatively, a wind-solar hybrid generator system has a cylinder for supporting a wind power generator, and a solar generator module, which is usually very small and is mounted on the cylinder. Because the middle portion of the solar generator module is directly and slantingly fixed to the cylinder, the solar generator module may be damaged by the strong wind if its area is too large. Thus, the conventional solar generator system still has to be improved.

Solar generator apparatus with suspending supports


Manufacturing costs may be reduced and yield may be improved when metal wiring in a semiconductor device is fabricated by a disclosed method including: sequentially forming an etch stop layer, an intermetal insulation layer, an anti-reflection coating layer, and a mask pattern on a semiconductor substrate formed with a lower structure; etching the anti-reflection coating layer using the mask pattern; forming a trench by removing the intermetal insulation layer to a predetermined depth by performing wet etching using the mask pattern; forming a via hole by removing the remaining intermetal insulation layer and the etch stop layer by dry etching them using the mask pattern; and removing the mask pattern.

Recently, as semiconductor integrated circuits have become more highly integrated and their operation speed has increased, metal lines in semiconductor devices have become narrower and multi-layered. In addition, copper wiring and low dielectric constant (low-k) materials have been proposed for minimizing the RC signal delay associated with such lines. Furthermore, patterning of wiring has become more difficult as the design rule has decreased, and, thus, a damascene process has been developed to skip a metal etching step and an insulator gap-filling step in a metallization process. Such a damascene processes may be categorized as single damascene and dual damascene processes. A conventional method of metallization by a dual damascene process will hereinafter be described as an example of a general damascene process.
An etch stop layer, an intermetal insulating layer, and an anti-reflection layer are sequentially formed on a lower metal layer. Then, a via mask is formed on the anti-reflection layer. A via hole is formed by selectively etching the anti-reflection layer and the intermetal insulating layer by the via mask and then ashing the mask.
After filling the via hole with a sacrificial layer (for example, formed of novolac), the sacrificial layer is recessed to a predetermined depth. Then, after coating an anti-reflection layer, a trench mask is formed. A trench is then formed by a dry etching process using the trench mask.
Subsequently, the trench mask and the sacrificial layer remaining in the via hole are removed by an ashing process. In addition, the etch stop layer exposed in the bottom of the via hole is removed to complete a dual damascene pattern including a via hole and a trench. A metallization process is then completed by subsequently forming a barrier metal layer in the damascene pattern, filling the damascene pattern with a conductive material such as copper, and polishing the conductive material.
In such a conventional method of fabricating metal wiring, mask patterns for a via hole and a trench are separately required, since the via hole is formed first and then the trench is formed. Therefore, a process for fabricating metal wiring is complicated since the dry etching process using the mask and the ashing process for removing the mask pattern are respectively performed twice, and a sacrificial layer is involved.
In addition, in the conventional method of fabricating metal wiring described above, when the sacrificial layer is not completely removed during the ashing process for removing the trench mask, the etch stop layer is also not completely removed. Accordingly, the contact resistance increases, thereby causing a degradation of device characteristics.
To clarify multiple layers and regions, the thickness of the layers are enlarged in the drawings. Wherever possible, the same reference numbers will be used throughout the drawing(s) and accompanying written description to refer to the same or like parts. As used in this patent, stating that any part (e.g., a layer, film, area, or plate) is in any way positioned on (e.g., positioned on, located on, disposed on, or formed on, etc.) another part, means that the referenced part is either in contact with the other part, or that the referenced part is above the other part with one or more intermediate part(s) located therebetween. Stating that any part is in contact with another part means that there is no intermediate part between the two parts.

Methods of fabricating metal wiring in semiconductor devices


The invention relates to a sealing device (11, 35, 41) for sealing a gap (32) between a lintel (30) and a roller shutter (10, 34, 40). The sealing device (11, 35, 41) has a sealing means (23) for arranging at the upper end of a top shutter element (24) of the roller shutter (10, 34, 40). For covering a gap (32) in a functional and/or cost-effective way between a lintel (30) and a roller shutter (10, 34, 40), preferably in case of a completely unrolled door blade (12), the sealing device (11, 35, 41) is characterized in that a swivel mechanism (25, 37, 43) is provided for swivelling the sealing means (23) from a sealing position into a winding position and from a winding position into a sealing position.

Field
The invention relates to a sealing device for sealing a gap between a lintel and a roller shutter, the sealing device has a sealing means for arranging at the upper end of a top shutter element of the roller shutter. Furthermore, the invention relates to a roller shutter for opening and closing a doorway, the roller shutter has a door blade, the door blade comprises several rigid shutter elements which are hinged with each other, the shutter elements are guided by side rails at opposed sides of the doorway.
Description of Related Art
Such a sealing device is known from the introductory description of document WO 2009/109274 A1.

Sealing device for sealing a gap between a lintel and a roller shutter and a roller shutter with such a sealing device


A converter device for an uninterruptible power supply, the device having first and second main switching units connected to first and second voltage lines of a first type and each equipped with a first main switch; a main switching point connected to a voltage line of a second type and connected to the first and second main switching units; and a third main switch common to the first and second main switching units, and connected between the main switching point and a third voltage line of the first type; first, second and third capacitors connected between the main switching point and each of the first, second and third voltage lines of the first type; a first auxiliary switching unit connected by individual auxiliary switches between the first and second voltage lines of the first type, and a first auxiliary switching point; a second auxiliary switching unit connected between the first, second and third voltage lines of the first type, and a second auxiliary switching point; and a transformer having windings each having one free end and one end connected to the main switching point, with the free ends respectively connected to the first and second auxiliary switching points.

The invention relates to the field of converters, such as boost converters and buck converters for example, as well as rectifiers and inverters, for example those used in uninterruptible power supplies, in particular in high-power uninterruptible power supplies, i.e. with a power generally comprised between about 100 and 500 kVA.
The invention relates more particularly to a converter device enabling first electric voltages available on a first, second and third voltage line of a first type to be transformed into a voltage on a voltage line of a second type, in either direction, said device comprising:                a first main switching unit connected to said first voltage line of the first type and equipped with a first main switch,        a second main switching unit connected to said second voltage line of the first type and equipped with a second main switch,        a main switching point connected to said voltage line of the second type and connected to said first and said second main switching unit, and        a third main switch common to said first and to said second main switching unit, said third main switch being connected between said main switching point and the third voltage line of the first type.
The invention also relates to an uninterruptible power supply comprising a power supply input on which an AC input voltage is applied, a rectifier connected to said input, two substantially DC voltage lines of opposite signs connected on output of said rectifier, and an inverter connected to said substantially DC voltage lines and comprising an output designed to supply a secured voltage.

Converter device for an uninterruptible power supply


A binder is described which comprises A) a hydrolysate or heterocondensate of at least one hydrolysable silicon compound and at least one metal, phosphorus or boron compound, the metal being selected from Al, Ge, Sn, Pb, Ti, Mg, Li, V, Nb, Ta, Zr and Hf, B) an organic polymerizable or polycondensable monomer or oligomer and C) a buffer, so that the pH of the buffered binder is in the range from 2 to 7, and optionally a complexing agent, if appropriate, the at least one hydrolysable silicon compound comprising one or more hydrolysable silicon compounds having at least one nonhydrolysable group or oligomers thereof. The binder is suitable for consolidating bulk or loose substrates.

1. Field of the Invention
The invention relates to a binder, methods for binding bulk materials and loose formations with this binder and bound products produced therewith.
2. Discussion of Background Information
Binders for binding bulk materials and loose formations are known. Thus, for example, DE-A-102004004615, EP-A-06706316, WO 2007/121972 and WO 2007/121975 describe systems which are used for consolidating bulk materials or loose formations. As a rule, a procedure is adopted in which a reactive soluble system is infiltrated into a bulk material or loose formation and is solidified via a reaction. Various materials are used for this purpose, for example organic monomers, hydrolysable and condensed alkoxides which are activated via sol-gel reactions, or mixtures of the two.
What is of decisive importance is that the solidification or curing reaction starts only when the infiltration process is complete. Otherwise, there is the danger that the binder will block, for example, feed lines or will solidify on the surface of the bulk material to be infiltrated and will not penetrate into the bulk material. The setting behaviour of the binder must therefore be adjusted so that solidification begins reliably only when the infiltration is complete or when a part of the binder is washed out or blown out again by a further step in order to maintain porosity.
In order to achieve this, the kinetics of the setting process must be well known and must be capable of being established in an exactly reproducible manner. For example, free radical polymerization mechanisms which have a known initial period are suitable for this purpose. It has been found, for example, that thermally initiatable peroxides are suitable as free radical formers. Pure sol-gel systems are also suitable but they show a strong dependence on external boundary parameters, such as, for example, pH and water content. These are so-called "living systems" whose stability declines with time so that they are frequently not particularly suitable for specific technical purposes.
The abovementioned prior art describes systems which were intended for the consolidation of bulk materials or loose formations. Mixed systems comprising sol-gel compositions, organic monomers or oligomers having reactive double bonds and initiators based on peroxides are described. The peroxides are chosen so that, after reaching the initiation temperature, a certain time elapses before a significant effect is found in respect of an increased viscosity of the system. The initiation temperature is the temperature at which the decomposition rate of the peroxides is sufficient for starting a polymerization chain reaction.
In this way, for example, a monomer solution which is provided with a corresponding initiator can be infiltrated into a bulk material which is kept at a specified temperature, and the consolidation can be induced after a specified time via the initial period peculiar to the initiator. Exact tailoring of the predetermined temperature of the bulk material, the decomposition temperature of the initiator and a knowledge of the enthalpy of reaction is required in order to avoid so-called "run-away" of the reaction and, as a result of this, consolidation at too early a stage.
However, the abovementioned prior art does not discuss the effect of finely divided components on the course of the chain or solidification reaction or take this into account. Thus, in our own investigations, it was found that finely divided components, e.g. phyllosilicates or milled ceramic components or oxides (clay minerals, Al2O3, ZrO2, Fe2O3, earthenware or stoneware), lead to early initiation of free radical formation from peroxide initiators, presumably due to catalytic effects at corners and edges of very fine particles present in the system. Thus, the addition of very fine oxide particles, such as fine clay minerals and finely milled ceramic particles, reduced the "open" time (time to gel formation or an increase in viscosity by several powers of ten) from about 4 hours to about 1 hour. Since no statement can be made about the presence, the type, the amount and the activity of such particles, particularly in natural formations which are to be bound, the presence of such particles in the systems to be bound is also an obstacle to the use of such binder systems in practice.
Systems described in WO 2007/121972 and WO 2007/121975 are scarcely suitable in practice owing to the abovementioned problems.
It was therefore the object to provide a binder which is suitable for binding bulk materials of all kinds or geological formations and ensures that it is not impaired in its mode of action by active surfaces of very fine particles, in particular with regard to the "open" time explained above. In particular, this should be achieved for binders with free radical initiators, such as peroxide initiators, on use of the above-described principle of free radical polymerization with a delayed action after the infiltration of bulk materials.
In addition, with the simultaneous use of polycondensable alkoxides, in particular with the use or concomitant use of silanes, the influence of the pH on the condensation process is considerable. This results in the danger that an influence, for example relating to the bulk material or formation, on the pH likewise has an influence on the open time. This too is not discussed in the above prior art.
It has now surprisingly been found that, by buffering reaction mixtures comprising precondensed sol-gel systems and organic binder components, such as monomers, with a buffer solution, in particular comprising an organic acid and a conjugated base, such as an acetic acid/acetate buffer, no influence at all of very fine particles on the properties of the binder is observable.

Binders for binding beds and loose formations and processes for producing them

EPG (Engineered Nanoproducts Germany) AG


A bearing housing (1) of an exhaust-gas turbocharger, having a compressor-side housing flange (2), a central housing section (3) which is integrally connected to the housing flange (2) and in which is arranged a first partial section (4) of an oil chamber (5) which has an oil inlet (20) and an oil outlet (21), and a turbine-side housing section (6) which has a turbine-side housing flange (7) and in which is arranged a second partial section (8) of the oil chamber (5). The central and turbine-side housing sections (3, 6) are provided with an oil cooling duct (13; 13′).

A bearing housing of said type is known from DE 43 30 380 A1. The known bearing housing is divided into a bearing insert and a bearing dish which at least partially surrounds the bearing insert. Here, an oil chamber for cooling the bearings of the bearing housing is formed in the bearing insert, which is a cast part. Even though it is sought by means of said arrangement to attain a simplification in construction and production, the design of the bearing insert with the oil chamber is cumbersome because it results in a relatively complicated geometry which cannot be produced easily by casting. Furthermore, the cooling of the bearing housing and of its bearings has room for improvement.

Bearing housing of an exhaust-gas turbocharger


The present invention relates to an antenna apparatus corresponding to a plurality of multi-bands, etc. and makes a plurality of radio communication frequencies easily changed or set. The present invention includes a passive element composed of a plurality of element units (elements 141, 142, 143) linked with a switching element (PIN diode) between the element units, and since the operating frequency of the passive element is switched by opening and closing the switching element and the passive element acts as a waveguide element, a radiation pattern can be acquired by the passive element and the effect of a human body is reduced on the radiant efficiency.

1. Field of the Invention
The present invention relates generally to an antenna corresponding to a plurality of radio communication frequencies, and more particularly, to an antenna apparatus and a radio communication apparatus including a passive element preferred for various radio communications such as a folding cellular phone.
2. Description of the Related Art
In a mobile telephone service such as a cellular phone, radio communication frequencies are increased and made multiband such as dual-band or triple-band as a coverage area is expanded, and an antenna corresponding to such frequencies is needed.
A radiant efficiency is an evaluation item of antenna characteristic and is improved relatively easily by a distance between an antenna and ground (GND) or by a matching circuit. Since a cellular phone is generally used by bring a receiver into contact with ear and the antenna comes closer to a human head, radiated electric waves are attenuated by the effect of a human body in no small way. As the extent of the attenuation of the radiated electric waves is increased, the radio communication may be disturbed. Since a plurality of resonance points exists in one antenna in the case of a multiband antenna, the radiant efficiency tends to be inferior to a single-band antenna.
Such an antenna apparatus with a plurality of resonance points includes Japanese Patent Application Laid-Open Publication Nos. 1998-190347, 1998-190344, 2004-304705, 2004-128557, etc.; Japanese Patent Application Laid-Open Publication No. 1998-190347 discloses a patch antenna apparatus corresponding to a plurality of frequencies, which is provided with a plurality of additional patch units connected by a PIN diode on a patch unit and which makes the PIN diode conductive and nonconductive to switch connection of the patch unit and the additional patch units; Japanese Patent Application Laid-Open Publication No. 1998-190344 discloses an antenna with a feed element and a passive element connected by a switching element, which changes a resonance frequency by opening and closing the switching element; Japanese Patent Application Laid-Open Publication No. 2004-304705 discloses a radio apparatus including a slot electromagnetically coupled to an antenna as well as a switch for shorting or opening a bottom board region of the slot, which switches radiation patterns of the antenna by opening and closing the switch; and Japanese Patent Application Laid-Open Publication No. 2004-128557 discloses an antenna including first and second antennas on a printed board, which changes electric length of the antennas to switch directional characteristics.
By the way, in a radio communication apparatus, such as a cellular phone, coming closer to a human body at the time of communication, since the radiated electric waves of the antenna are affected by a human body in no small way and the effect thereof cannot be eliminated completely, an antenna apparatus corresponding to the multiband is needed. That is, an antenna apparatus is requested which enhances the radiant efficiency, which reduces the effect of a human body, and which is suitable for the multiband.
Japanese Patent Application Laid-Open Publication Nos. 1998-190347, 1998-190344, 2004-304705, and 2004-128557 do not disclose or indicate such problems and do not disclose or include a concept of an antenna apparatus that solves the problems.

Antenna apparatus and radio communication apparatus


Disclosed are mutant CDK inhibitor (CKI) polypeptides having dominant negative antagonist activity against wild-type CKI proteins, as well as related compositions, including nucleic acids and vectors encoding the mutant CKI polypeptides and transformed host cells and transgenic plants comprising such nucleic acids and vectors. Also disclosed are related methods for using the mutant proteins to modulate cell division in cells, particularly plant cells.

Plants have the same basic cell cycle as eukaryotes. Not surprising, they also have in common with eukaryotes kinases called cyclin dependent kinases (CDK) that regulate the transitions between different phases of the cell cycle. Arabidopsis, a model plant system used to study the cell cycle have several CDK sub-groups. CDKA is most similar to the cdc2 (CDK1) of mammals and contains the highly conserved Pro Ser Thr Ala Ile Arg Glu (PSTAIRE) amino acid sequence (SEQ ID NO:1) in a region that mediates the interaction with their cyclin partner. Arabidopsis also has a plant-specific group of CDK called CDKB that is not conserved in higher animals. Plants do however lack the mammalian counterpart to the G1 CDKs-CDK4 and CDK6. CDKA has been proposed to be the G1 CDK (that is activated by the plant D-type cyclins), while CDKB has been demonstrated to be predominantly expressed in S-phase and later and, therefore, likely identified as the G2/M specific CDK.
Activation/inactivation of these CDKs drives cells through the cell cycle and also dictates when cells are to exit the cell cycle. Arabidopsis contains up to 49 cyclins grouped into 10 subclasses (see Wang et al., Plant Physiol. 135:1084-1099, 2004). Only the A, B and D-classes appear to play a role in the cell cycle and activate CDKs (Wang et al., Plant Physiol. 135:1084-1099, 2004). CDKA is activated by the D-type cyclins, while CDKB is activated by A- and B-type cyclins.
In animals CDKs are negatively regulated by two families of CDK inhibitors (CKIs). One class, called inhibitor of CDK4 (INK4) is comprised of 4 members (p15, p16, p18 and p19) that bind to and inhibit the G1 CDKs, namely CDK4 and CDK6, from binding the cyclin. The other group of inhibitors is called Kinase Inhibitor Proteins (KIPs) or CIP (CDK Interacting Protein) proteins and they are highly conserved in all animals. The CIP/KIP family predominantly inhibit the cyclin A- and E-CDK2 kinase activity. In plants, putative CKIs have been identified (Wang et al., Nature 386:451-452, 1997; Wang et al., Plant J. 15:501-510, 1998; De Veylder et al., Plant Cell 13:1653-1667, 2001; Jasinski et al., Plant Physiol. 130:1871-1882, 2002) and shown to inhibit purified cyclin/CDK kinase activity in vitro (Wang et al, 1997, supra; Wang et al., Plant J. 24:613-623, 2000; Lui et al., Plant J. 21:379-385, 2000). Expression of plant CKIs showed reduced growth with smaller organs containing larger cells (see Wang et al., 2000, supra; Jasinski et al., J. Cell Sci. 115:973-982, 2001; De Veylder et al., supra; Zhou et al., Plant Cell Rep. 20:967-975, 2002; Zhou et al., Plant J. 35:476-489, 2003; Schnittger et al., Plant Cell 15:303-315, 2003). In Arabidopsis, these CKIs, are called Inhibitors of CDK (ICKs) or KIP related proteins (KRPs). Seven ICK family members have been identified that most closely resemble the CIP/KIP family of CKIs. Each of these ICK/KRP family members has high amino acid sequence identity to p27KIP1 but the identity is limited to the most C-terminal 30 amino acids. To date, no INK related CKIs have been identified in any plant.
Over expression of cyclins or knockouts of CKI illustrate that the well balanced cell cycle engine can easily be perturbed in mammals. This imbalance can ultimately lead to accelerated cell cycles, increased animal size and/or tumor development. Reducing or completely eliminating CKI "activity" results in increased cyclin/CDK kinase activity. This increased activity results in phosphorylation of downstream targets necessary for cell cycle progression and animals ultimately yields cell hyper-proliferation (Coats et al., Science 272:877-880, 1996). Deletion of the p27KIP1 gene in mice results in larger mice due to excessive cyclin/cdk activity that leads to excessive cell proliferation (Fero et al., Cell 85:733-744, 1996; Kiyokawa et al., Cell 85:721-732, 1996; Nakayama et al., Cell 85:707-720, 1996).
Mechanisms exist to suppress expression of various members of the KRP family. Post-transcriptional gene silencing (PTGS) in plants is an RNA-degradation mechanism similar to RNA interference (RNAi) in animals. RNAi results in the specific degradation of double-stranded RNA (dsRNA) into short 21-23 bp dsRNA fragments which ultimately play a role in the degradation of a population of homologous RNAs. In plants, PTGS uses an inverted repeats (IR) strategy to suppress gene expression in many plants species including crop plants such as corn, soy and Canola to name a few. However, IR technology has several drawbacks such as the efficiency of IR sequence, off target gene regulation (Jackson et al., Nature Biotech. 21:635-637, 2003), transient silencing, overall IR stability, and the like. These drawbacks are compounded in the present case by the need to silence more than one gene at a time.
Conventional plant breeding has been the principle driving force for increased crop yields over the past 75 years (J. Femandez-Cornejo, Agriculture Information Bulletin No. (AIB786) 81 pp, February 2004). More recently, transgenic crops have become available that for example have resistance to insect pests and herbicides. However, these transgenic crops do come with a yield penalty (Elmore et al., Agron. J 93:408-412, 2001; Elmore et al., Agron. J. 93:404-407, 2001). To date, no known transgenic crop is commercially available that has an increase in seed size or an increase in crop yield.
There is a need in the art for improved methods of modifying characteristics of certain commercially valuabile crops, including for example, but not limitation, increasing crop yields, increasing seed size, increasing the rate of germination, increasing root mass, and the like. The present invention as described herein meets these and other needs.

Dominant negative mutant KRP protein protection of active cyclin-CDK complex inhibition by wild-type KRP


There are provided an optical transceiver, an optical network unit, and an optical transceiver control method that control the operating state of the optical transceiver and reduce the number of terminals of the optical transceiver. An optical transceiver includes: a transmitting and receiving unit that transmits and receives optical signals and that has three or more states for transmission or reception of the optical signals, the states transitioning in sequence; a terminal for receiving a voltage or current as operation instruction information indicating in which one of the states operation is to be performed; and a determining unit for determining one of the states indicated by the operation instruction information, based on a magnitude of the voltage or current received by the terminal. The transmitting and receiving unit operates in the one of the states determined by the determining unit.

In recent years, the Internet has proliferated widely. Thus, users can access various information on sites run around the world and obtain the information. Accordingly, apparatuses capable of performing broadband access such as ADSL (Asymmetric Digital Subscriber Line) and FTTH (Fiber To The Home) have also been widely used at a rapid pace.
IEEE Std 802.3ah (registered trademark)—2004 (Non-Patent Literature 1) discloses one system of a passive optical network (PON) which is medium-sharing communication where a plurality of optical network units (ONUs) perform data transmission with an optical line terminal (OLT) by sharing an optical communication line. Specifically, there are defined EPON (Ethernet (registered trademark) PON) where all pieces of information including user information passing through the PON and control information for managing and operating the PON are communicated in Ethernet (registered trademark) frame format; and an access control protocol (MPCP (Multi-Point Control Protocol)) and an OAM (Operations Administration and Maintenance) protocol for EPON. By exchanging MPCP frames between the optical line terminal and the optical network units, joining, leaving, and upstream access multiple control of the optical network units, etc., are performed. In addition, Non-Patent Literature 1 describes a new-optical network unit registration method, a report indicating a bandwidth allocation request, and a gate indicating a transmission instruction, by MPCP messages.
Note that even in 10G-EPON which is standardized as IEEE 802.3av (registered trademark)—2009 as the next-generation technology of GE-PON (Giga Bit Ethernet (registered trademark) Passive Optical Network) which is EPON achieving a communication speed of 1 gigabit per second, i.e., EPON whose communication speed is equivalent to 10 gigabits per second, an access control protocol is premised on MPCP.

Optical transceiver, optical network unit, and optical transceiver control method


The present invention relates to [1] a water-based ink for ink-jet printing which can be prevented from suffering from increased viscosity and flocculation of the ink upon storage thereof even when used in the form of a system containing a large amount of a solvent, said water-based ink for ink-jet printing containing crosslinked polymer particles containing a pigment having an indanthrone skeleton, an organic solvent and water, in which a crosslinking rate of the crosslinked polymer is not less than 10 mol % and not more than 90 mol %, and a content of the organic solvent in the water-based ink is not less than 30% by mass and not more than 65% by mass, and [2] an ink-jet printing method including the steps of loading the water-based ink as described in the above [1] to an ink-jet printing apparatus, and ejecting the water-based ink in the form of droplets of the ink onto a printing medium to form characters or images on the printing medium.

In ink-jet printing methods, droplets of ink are directly ejected onto a printing medium from very fine nozzles and allowed to adhere to the printing medium to form characters or images thereon. The ink-jet printing methods have become rapidly spread because of various advantages such as easiness of full coloration, low cost, capability of using a plain paper as the printing medium, non-contact with printed characters or images, etc.
In recent years, in order to impart good weathering resistance and water resistance to printed materials, an ink for ink-jet printing which contains a pigment as a colorant has been extensively used. As the pigment, there have been used those pigments having process colors, i.e., a yellow pigment, a magenta pigment, a cyan pigment and a black pigment. Upon production of the ink using the pigments having process colors, in order to enhance storage stability of the ink, there has been employed such a method in which a polymer dispersant used for dispersing the pigments is subjected to crosslinking reaction, or the like.
For example, JP2008-156465A (Patent Literature 1) discloses a water-based ink for ink-jet printing as an ink using a crosslinked polymer, which contains crosslinked polymer particles containing C.I. Pigment Yellow 74 and a polar group-containing pigment derivative, in which the crosslinked polymer particles are obtained by crosslinking a polymer with a compound containing two or more reactive functional groups in a molecule thereof.
In addition, in recent years, in order to expand a reproducible region of various colors, there have been used pigments having special colors such as red, green, blue, orange, violet, etc.
For example, JP2005-15813A (Patent Literature 2) discloses an ink set for ink-jet printing which contains a cyan ink composition containing at least one pigment selected from the group consisting of C.I. Pigment Blue 60, C.I. Pigment Blue 22, C.I. Pigment Blue 64 and C.I. Pigment Blue 21.
Moreover, JP2003-94792A (Patent Literature 3) discloses an ink-jet printing method for printing images, etc., on a printing medium using pigment inks containing a yellow pigment, a magenta pigment and a cyan pigment, respectively, in which the printing medium has a specific gloss, a specific surface roughness and a specific penetration rate, and at least one of the pigment inks contains pigment particles having a specific zeta potential. In Examples of Patent Literature 3, it is described that the ink set prepared by dispersing C.I. Pigment Blue 60 with an acrylic-styrene-based resin was used.


A device for ophthalmic surgery includes a vacuum-pump arrangement for generating a vacuum serving for fixing a suction ring to an eye, an evacuation-path system for transmitting the vacuum to an interface port which permits the separable attachment of a suction-ring instrumentarium including the suction ring, and also a control unit for controlling the vacuum-pump arrangement. In accordance with the invention, the device includes pressure-measuring components for measuring at least the vacuum pressure, the control unit adapted to ascertain a differential pressure between the measured vacuum pressure and an atmospheric pressure. The vacuum-pump arrangement is preferably operated at maximal pumping power in a test-operation mode with suction-ring instrumentarium not attached, in order to ascertain an optimally obtainable relative underpressure in the evacuation-path system. In this way, in the case of fluctuating altitudes of the location of use of the ophthalmic-surgery device and also in the case of fluctuating weather conditions (low pressure, high pressure) it can be ascertained at all times whether the achievable relative underpressure is sufficient.

A device of such a type may come into operation, for example, within the scope of a microkeratome, i.e. in the case of a microsurgical plane such as is used, for example, for the placement of a flap incision on a human eye. Such a flap incision is necessary within the scope of a form of operation customarily known in specialist circles as LASIK (laser in-situ keratomileusis). By means of the flap incision, in this case on the surface of the cornea a small disc (flap) is cut out which on a part of its periphery is still connected to the remaining corneal tissue and can therefore be folded aside and subsequently folded back again without difficulty. Depending on whether the flap incision extends within the stroma or within the epithelium on Bowman's membrane, in specialist circles one customarily speaks of classical LASIK or Epi-LASIK, respectively.
In the case of a microkeratome, the suction ring is needed not only for the purpose of fixing the eye but customarily also for the purpose of coupling and guiding a cutting unit equipped with a cutting blade, which, as a rule, is held in the hand by the operating surgeon and is therefore frequently also designated as a handpiece of the microkeratome. Also customarily part of the handpiece is a motorised drive unit which serves for generating the cutting motion of the cutting blade. In the case of a microkeratome marketed by WaveLight under the trade name RONDO, the cutting blade has, like a razor, a rectilinear cutting edge and is moved linearly, subject to high-frequency lateral oscillation, in the direction perpendicular to the cutting edge. The cutting blade is, for example, held in a cutting head which is separably and consequently interchangeably coupled with a drive module of the handpiece.
The suction-ring instrumentarium may include, in addition to the actual suction ring, further components which, for example, serve for transmitting the vacuum from the interface port to the suction ring. For example, these components may include a hose line with a suitable connector for connecting to the interface port. At the end remote from the interface this hose line may have been separably connected to a connecting piece of a suction-ring unit forming the suction ring and, for example, produced in one piece. It should be pointed out that the suction-ring unit may perfectly well exhibit several hose-line ports which permit the attachment of several hose lines, particularly if the suction-ring unit exhibits several evacuation spaces (suction chambers) that are capable of being evacuated separately. For the purpose of fixing the suction ring to the eye, said suction ring customarily exhibits an annular chamber delimited exclusively between the suction ring and the surface of the eye.
A device according to the invention may, alternatively or additionally, come into operation within the scope of a cutting machining of the human eye using laser technology. Relevant laser systems often provide for the interposition of an adapter between the eye to be machined and an objective which focuses the laser radiation onto the eye. The adapter brings about a positioning of the eye in relation to the laser system, facilitating the accurately targeted generation of the incision. In this connection it is known to construct the adapter with a contact element that is transparent to the laser radiation and that is brought into planar contact with the eye. In the case of a plane contact surface of the contact element, a levelling of the cornea takes place; one therefore speaks of an applanation element.
By reciprocal coupling of the suction ring, which in turn is firmly aspirated on the eye, and of the adapter, for instance by aspirating the adapter onto the suction ring, it is possible to position the eye precisely and securely in relation to the laser system.
Regardless of the form of the operation in which the suction-ring instrumentarium is being employed, a sufficiently intense vacuum is necessary, in order that the suction ring remains firmly aspirated on the eye reliably during the operation. As a rule, the vacuum-pump arrangement is dimensioned so as to be sufficiently powerful in order to be able to build up the requisite vacuum under normal conditions. An overdimensioning of the vacuum-pump arrangement is of course not desirable as a rule, for reasons of cost and construction space.
The achievable quality of the vacuum depends not only on the maximal pumping power of the vacuum-pump arrangement but also on the altitude of the location of use and on the current weather situation. For given pumping power, the achievable vacuum pressure depends on the current atmospheric pressure at the location of use, in which connection this atmospheric pressure may fluctuate more or less intensely, depending on the altitude of the location of use and depending on the state of the weather (high pressure, low pressure). This may have the consequence that, under certain circumstances, in the case of a location of use situated at a great height only a considerably smaller operating range of the vacuum than under lowland conditions is available. Even if the user presets a certain nominal value of the relative underpressure ('relative underpressure' means the level of the underpressure in relation to the environment) at an operating console, the relative underpressure actually achieved may be substantially lower (e.g. −500 mmHg instead of a value desired by the user of, for example, −600 mmHg) and therefore may under certain circumstances give rise to surgical dangers.


A device includes an enclosure mounted to an end portion of a photovoltaic panel and has an interior, an opening, an inclined ramp within the interior, a door pivotally disposed at the opening, and a latch mechanism. The door is on a panel surface in an open position, and blocks the opening in a closed position. The latch mechanism latches the door closed and releases the door to the open position. A flexible material blocks light from reaching panel photovoltaic cells and includes a first end coupled to the inclined ramp within the enclosure and an opposite second end coupled to a rod. The flexible material is rolled up about the rod and rests on the inclined ramp. The door's closed position blocks deployment of the material. In the open position, the material rolls down the inclined ramp and covers the panel surface. The door is automatically or manually deployed.

1. Field
The disclosed concept pertains generally to photovoltaic panels or arrays and, more particularly, to protection devices and systems therefor. The disclosed concept further pertains to photovoltaic systems.
2. Background Information
Power sources that generate electrical energy usually contain a mechanism to shut off the source of power when the electrical energy is no longer needed, or if there is danger of causing harm to people or equipment.
For example, an electromechanical generator has a prime source of power, such as a gas or diesel engine. In an emergency condition, the source of fuel can be turned off (e.g., by a valve) or the engine can disconnected from the generator, thereby allowing the generator to spin down, stop and cease producing energy.
For alternative energy sources, such as windmills having turbines or wind turbines to generate energy, the turbine can be disconnected from the rotor blades moving the turbine in order to stop the generation of energy. Alternatively, the rotor blades can be rotated to stop the creation of lift on the rotor blades and cause them to stop spinning, thereby stopping the turbine from spinning and creating electrical energy.
U.S. Patent Application Publication No. 2011/0172842 discloses the use of switches to shut down an attached solar module. The switches can be mechanical switches, semiconductor-type switches, such as MOSFET transistors or other similar switches, or any suitable type of switch.
U.S. Patent Application Publication No. 2010/0071744 discloses a photovoltaic (PV) installation including a PV array, an electrical interface connecting a utility power source to an electrical load, and a DC to AC inverter. A first set of wiring electrically connects the PV array to the inverter through a disconnect device and a second set of wiring electrically connects the inverter to the electrical interface. A control mechanism connects the disconnect device to the electrical interface, in order that when power from the electrical interface is removed, the PV array is electrically disconnected from the inverter. The disconnect device may be a remote disconnect device located at a position at or near the PV array, such as in the space beneath a roof supporting the PV array.
However, these proposals do not prevent photovoltaic cells from providing a potential voltage that could feed a fault between a photovoltaic panel and a first switch or disconnect device. As a result, there is an area where there is no protection. As long as the sun or another source of light is shinning on the photovoltaic or solar cells, they produce electrical energy. This is more evident when there are relatively many cells in an area and relatively long runs of cabling combine the cells to create higher voltages and/or larger current capabilities. There have been recent instances of such cells creating fires because of loose wiring or short circuits. There is also an electrocution danger to first responders to a location with cells generating electrical energy because the responders cannot completely turn off the cells.
FIG. 1 shows a photovoltaic generation and distribution system including a plurality of photovoltaic or solar cells 1, distribution wire 2, a first DC disconnect or circuit breaker 3, an inverter 4 for converting DC voltage to an AC voltage, a grid interconnection circuit breaker 5, and an electrical grid or a number of electrical loads 6. A zone of no protection 7 exists when the cells 1 are generating electrical energy. The zone of no protection 7 is where the cells 1 can produce unwanted electricity at a time when, for example, workers, firemen or first responders to an emergency are in the area. This zone of no protection 7 is also prone to relatively high current faults, arcing faults and ground faults.
FIG. 2 shows another photovoltaic generation and distribution system that is somewhat similar to the system of FIG. 1, except that it is larger, includes more photovoltaic or solar cells 1 and more distribution wire 2 to combine the multiple cells. Hence, the corresponding zone of no protection 7′ has expanded with more distribution wiring and with multiple photovoltaic panels including the cells 1.
U.S. Patent Application Publication No. 2012/0174961 discloses a photovoltaic system including one or more solar panels, and one or more shuttering assemblies, each of which is configured to selectively limit the quantity of light received by one or more of the solar panels. A control module is configured to direct the one or more shuttering assemblies to reduce the quantity of light received by at least one of the one or more solar panels in response to signals indicating there is an arc fault event in the photovoltaic system. The shuttering assembly includes an elongated, opaque sheet that is biased into a wound or stowed position. The sheet is movable via a motor from the stowed position to an unwound or blocking position in which the elongated sheet extends across and substantially covers the light-receiving surface of the string of solar panels.
There is room for improvement in photovoltaic panels and arrays.
There is also room for improvement in photovoltaic systems.

Device for disabling a photovoltaic panel or array and photovoltaic system including the same


An air conditioner, having an outdoor unit and an indoor unit, to perform a heating operation and a defrosting operation, the air conditioner including a detection unit to detect a state of at least one selected between the outdoor unit and the indoor unit and to output the detected value, a controller to determine whether the air conditioner is in a stable state when the defrosting operation is completed and, upon determining that the air conditioner is in the stable state, to control the detected value output from the detection unit to determine entry time of the next defrosting operation, and a storage unit to store a value detected in the stable state. The entry time of the defrosting operation is accurately determined, thereby minimizing the number of times of the defrosting operation during the heating operation.

1. Field
Embodiments of the present disclosure relate to an air conditioner to control a defrosting operation and a control method thereof.
2. Description of the Related Art
An air conditioner is a device that cools, heats, or purifies and discharges suctioned air using movement of heat generated during evaporation and condensation of refrigerant to condition air in an interior space.
In summer, the air conditioner performs a cooling operation to discharge heat out of a room. In winter, the air conditioner performs a heating operation of a heat pump to supply heat into the room by circulating refrigerant in reverse order of a cooling cycle.
When the air conditioner performs the heating operation, an outdoor heat exchanger of an outdoor unit absorbs heat as the result of evaporation. At this time, the surface temperature of the outdoor heat exchanger is greatly reduced with the result that condensed water is formed on the surface of the outdoor heat exchanger.
When the temperature of the outdoor heat exchanger is 0° C. or less, the condensed water does not fall down the outdoor heat exchanger but is frozen on the surface of the outdoor heat exchanger.
The condensed water frozen on the surface of the outdoor heat exchanger reduces a heat exchange area of the outdoor heat exchanger. As a result, heat exchange performance of the outdoor heat exchanger is reduced. In addition, heating efficiency of the air conditioner and reliability of a compressor are deteriorated.
For this reason, the air conditioner performs a defrosting operation, in which the refrigerant is circulated as in the cooling operation, to defrost the outdoor heat exchanger.
That is, when the cooling operation is performed during the heating operation, the refrigerant in the outdoor heat exchanger is condensed with the result that the refrigerant radiates heat, which defrosts the outdoor heat exchanger.
In the defrosting operation, however, the refrigerant flows in the same direction as in the cooling operation during the heating operation. Consequently, two-phase refrigerant, which is not overcooled, passes through an expansion valve of an indoor unit with a result that noise is generated.
In addition, the air conditioner uses change in temperature of the outdoor heat exchanger to determine entry time of the defrosting operation. When outdoor temperature is low, lowering of evaporation pressure for heat exchange between the outdoor heat exchanger and outdoor air may not be differentiated from lowering of evaporation pressure due to frost on the outdoor heat exchanger with the result that the entry time of the defrosting operation may not be accurately determined.
Consequently, the defrosting operation may be frequently performed even when the outdoor heat exchanger is unfrosted or the defrosting operation may be performed in a state in which the outdoor heat exchanger is excessively frosted. In the latter case, the outdoor heat exchanger may not be sufficiently defrosted.

Air conditioner and control method thereof


A bonding surface extraction unit extracts, with reference to bonding information, data of a first bonding surface corresponding to a bottom surface of a bonding model from data of a first partial model and data of a second bonding surface corresponding to a top surface of the bonding model from data of a second partial model. The first partial model is a model of a pad included in a circuit board. The second partial model is a model of an electrode included in a component. The electrode is to be bonded to the pad with a bonding material. A bonding model generation unit generates a side surface establishing a link between outlines of the first bonding surface and the second bonding surface, and obtains data of the bonding model on the basis of a shape formed with the side surface, the first bonding surface, and the second bonding surface.

Usually, the design of a circuit board has been performed with computer aided design (CAD). With the above-mentioned design which is referred to as the packaging design CAD (or the layout CAD), a computer arranges wiring with interactive processing and/or automatic processing on the basis of circuit-connection information (a net list) or information about a component to be mounted on the circuit board to obtain a desired circuit function.
After finishing the packaging design, the circuit board is generated on the basis of CAD data. Before generating the circuit board, the CAD data is often subjected to a structural analysis simulator to confirm the mechanical strength of the circuit board. For example, it is confirmed, on the basis of the analysis result, whether the strength of the bonding part of the mounted component is impervious to a stress applied to the circuit board when the circuit board is handled and provided in a cabinet.
In the field of the above-mentioned structural analysis, an analysis method based on the finite element method has been available. According to the above-mentioned method, a three-dimensional model to be analyzed is mesh-divided, that is, divided into a set of elements with small regions, and the entire behavior is predicted on the basis of the behavior of each of the elements with the small regions. Therefore, in general, two-dimensional CAD data of the circuit board, which is generated with the packaging design CAD, is converted into three-dimensional model data (hereinafter, the model data is often referred to as a model), and the three-dimensional model data is subjected to the structural analysis simulator. At that time, it is assumed that no bonding material such as solder is used for the part where a pad of the circuit board is bonded to an electrode of the mounted component, that is, the bonding material is ignored. Otherwise, a circular cylinder or a prism is generated as a simple bonding model and added to the three-dimensional model of the circuit board. Then, the three-dimensional model is subjected to the structural analysis simulator. FIG. 8A illustrates a three-dimensional model of a finished circuit board having components that are mounted on the circuit board on the basis of two-dimensional CAD data of the circuit board. Pads 11 to be bonded to mounted components are provided on a circuit board 10, and a ball grid array (BGA) type component 20, a chip type component 30, and a quad flat package (QFP) type component 40 are arranged over the pads 11 as the mounted components. The two-dimensional CAD data does not include data related to the shape of a bonding material such as solder used to bond the pad 11 to the mounted components. Therefore, the mounted components are arranged and floated above the pad 11 by as much as a specified amount determined to be the thickness of the bonding material. FIG. 8B illustrates a case where simple bonding models 50, 51, and 52 are added to the three-dimensional model illustrated in FIG. 8A. The simple bonding model denotes a bonding model including a bonding material such as solder having the shape of a circular cylinder or a prism. Traditionally, the above-mentioned simple bonding model has been used to perform a structural analysis. FIG. 8C illustrates a case where the bonding model is omitted and the mounted components are directly bonded to the pads 11. Traditionally, a mechanical simulation has been performed on the three-dimensional model illustrated in FIG. 8B or FIG. 8C.
FIG. 8D illustrates examples of actual shapes of bonding parts 60, 61, and 62 where the pads are bonded to the mounted components. That is, the actual shape of the bonding part is significantly different from that of the simple bonding model.
In a related matter, the following technology of generating an analysis model of a bonding part has been available. When first and second structural members are bonded to each other with a bonding member which is a third structural member having small thickness, a first and second bonding points are provided on the first and second structural members, respectively, where the first and second structural members are bonded to the third structural member at the first and second bonding points, respectively, and the first and second bonding points are restricted in accordance with a relation achieved on the basis of the physical property of the third structural member. Japanese Laid-open Patent Publication No. 2009-3529 discloses a related technology.

Bonding model generation apparatus and bonding model generation method


Aluminum-silicon alloys having high stiffness are used in forming computer memory disks and actuator arms. Disks formed with the alloy have low flutter and can be spun at 12,000 RPM or greater with a flutter of 10 .ANG. or less.

Various techniques for forming high performance metal alloys by powder metallurgy are known. Generally, these techniques involve forming a metal powder or particulate by atomizing a melt of the alloy, and then cooling the atomized alloy stream to effect solidification. Oftentimes, this process results in an alloy having a microstructure unachievable using more conventional techniques such as casting. It is thus possible to produce alloys having unusual physical properties.
Various applications might benefit from the improved physical properties afforded by metal powder materials. One of these applications is memory disk drives used in computers, commonly referred to as "hard disks" or simply "disk drives." Disk drives are formed of multiple parallel spaced disks each having a metallic substrate, usually nickel plated aluminum, with a magnetic coating. In use, the disks are rotated at high speeds, and an actuator arm scans over each disk to read and write digital programming.
Disk performance (i.e., memory capacity and read/write speed) is a function of the disk rotational speed. The faster the disks rotate, the greater the performance. Much effort has therefore been focused on the goal of increasing the disk speed.
However, achievement of this goal has been elusive. Currently, the upper limit on disk speed is approximately 7200 rpm using the industry standard 5000 series (5XXX) monolithic aluminum disk substrate. This upper limit is dictated by practical limitations on the amount of flutter permissible. Flutter is a phenomenon whereby the revolving disk begins to wobble above a certain rotational speed. If severe enough, flutter will result in the disk impacting against the actuator arm, which in turn may damage the disk and cause the disk drive to break down or "crash." Minimal flutter is therefore a prerequisite for preventing disk drive crashes and/or allowing higher disk speeds.
Several factors contribute to flutter. One is resonance caused by the interaction of the natural frequency of the disk and its rotational speed. The higher the natural frequency, the higher the rotational speed possible without resonance. The easiest way to increase the natural frequency of the disk, and hence "shift" the resonance point to a higher rotational speed, is to increase disk stiffness. Another factor influencing flutter is disk unevenness. Generally, the more uneven the disk surface, the greater the amount of wobble or flutter at a given rotational speed.
Hence, two desirable attributes of a metallic disk material are high stiffness and the ability to be highly machined and polished to a flat surface, thereby providing a high natural frequency and smooth surface finish. Furthermore, flutter can be attenuated by dampening factors contributed by composite materials. A ceramic material incorporated into a matrix (e.g. aluminum) provides a dampening factor which is a function of the interfacial surface area of the particles and the matrix. As the interfacial surface area increases, so does the dampening factor.
Various metal alloys and composite materials are known to have increased stiffness compared to monolithic aluminum. For several reasons, however, these materials are not wholly satisfactory for use in computer disks. For example, it is known to manufacture disks of silicon carbide or boron carbide in an aluminum matrix alloy. These composite materials are very stiff, having a modulus of about 14-30 msi. However, they are also very difficult to grind and polish to obtain a flat surface. Grinding rates are dramatically reduced compared to those for monolithic aluminum when using conventional grinding apparatus. This alone makes silicon carbide and boron carbide alloys impractical for commercial use in manufacturing computer disks. Another problem with polishing known prior art alloy materials is the hardness of the discontinuous phase. Grinding quickly dulls cutting tools and results in galling of the aluminum matrix. In addition, boron carbide or silicon carbide particles are literally pulled out of the aluminum matrix at the grinding surface, resulting in increased surface porosity.
In addition to minimizing flutter, a highly polished surface is necessary for proper coating of the substrate disk with a nickel plating. Without a highly polished surface, the plating will not be uniform. Gaps formed in the plating due to the lack of uniformity cause the subsequently applied magnetic coating to have imperfections, which in turn interfere with disk function.
A prior art process for forming metal alloyed memory disks is disclosed in U.S. Pat. No. 5,554,428. This patent teaches an aluminum alloy having various alloying elements such as zinc, copper, and dispersoid-forming elements of which scandium is one example. Disks are formed using casting and rolling.
U.S. Pat. No. 5,437,746 relates to a process for forming an aluminum alloy sheet which employs forming the aluminum alloy into an ingot or continuously cast thin sheet coil, followed by optional hot rolling, cold rolling and punching the alloy to produce a blank disk. The alloy includes magnesium, zinc, and copper.
The disks formed by these processes suffer from many of the disadvantages noted above. Hence, there remains a need in the art for a method for forming a disk having high stiffness and superior polishing characteristics. It would further be advantageous to manufacture actuator arms and various other components of a disk drive form the same or similar high stiffness alloy.

Aluminum-silicon alloy formed from a metal powder

California Consolidated Technology, Inc.