A process for producing and purifying peptides and for producing peptide/protein antigens for antibody production is described. The process utilizes fusion proteins and specifically fusion proteins in which the fusion protein carrier segment includes an amino acid sequence at least about 65 amino acids long and in which the amino acid sequence does not contain negative or positive charged side chains of amino acids.

A full bibliographic citation of the references cited in this application can be found in the section preceding the claims.
The present invention generally relates to markets where the detection or purification of molecules is involved. Representative markets include in vitro and in vivo diagnostics, research products, clinical products, clinical research products, pharmaceuticals and many industrial markets. These markets necessarily require a tight binding and specific affinity ligand that recognizes the biomolecule of interest. Given the importance of affinity recognition for proteins in a wide variety of markets, new methods for generating xe2x80x9cimmunoaffinityxe2x80x9d or xe2x80x9cmacromolecular recognitionxe2x80x9d ligands using DNA technology are sought.
The production of proteins and peptides by recombinant DNA technology is now relatively common. Recombinant expression of peptides often is accomplished by inserting a DNA sequence encoding the desired peptide into an expression vector. The expression vector generally contains regulatory sequences which are recognized by the host cell, and which provide for transcription and translation of the inserted DNA to produce the peptide. The expression vector is inserted into a suitable whole cell, typically a procaryotic organism, in culture. The expression vector also usually includes a selectable marker, so that one may identify those cells which have been transformed successfully and carry the vector, and separate them from those which do not carry the vector.
Peptides may be expressed either directly or in the form of a fusion protein. Direct expression involves the production of the desired protein or peptide without modification. However, this form of expression often results in low yields and degradation of the product, particularly with small peptides.
One method commonly employed to increase the yield of the desired peptide is to express it as part of a fusion protein. In this approach, a leader protein, hereafter referred to as a carrier segment, is selected which is expressed easily in the host of choice. Often this protein is native to the host, as in the case of xcex2-galactosidase. An expression vector encoding the carrier segment then is modified using standard molecular cloning techniques to express the desired peptide linked to the carrier segment. Most often, the peptide is linked to the carboxy terminus of the carrier segment but, in principle, it could be linked anywhere through a normal peptide linkage.
The expression of the peptide as a fusion protein with the carrier segment may imbue it with new, favorable properties. For instance, the fusion protein can be injected into a host animal to create antibodies to the peptide or to produce a vaccine. The technology of using fusion proteins as antigens is well-known to the art (Current Protocols, 1994, Chapter 16). Other favorable properties of the fusion protein may include ease of purification, the ability to be immobilized on surfaces, and the creation of bifunctional molecules (Santo, C. et al. 1992).
Although peptides with desired additional properties are commonly produced by the use of fusion proteins, it is also common to produce a peptide separately through chemical synthesis. The peptide then can be covalently coupled to purified carrier segments using chemical crosslinking agents. The resultant carrier protein conjugate can be used in many of the same applications as the fusion protein described above.
For example, peptides are sometimes covalently coupled to keyhole limpet hemocyanin for immunizations or to alkaline phosphatase for use as a detection reagent. In the case of the fusion protein, the only molecules which can be linked to the carrier segment are peptides, and the linkage must be through the normal polypeptide backbone.
When the second molecule is coupled chemically to the carrier segment after expression, the nature of both the second molecules, called ligands, and of the chemical linkages to the carrier segment is much broader. Any ligand and crosslinker which is chemically allowed can be contemplated.
In some cases, covalent association of the ligand (peptide, hapten, or other) with the carrier segment is not required to be effective. The two molecules associate with each other by any number of means. In this case, the mixture of the two is called a carrier protein complex.
The following paragraphs illustrate some uses of prior art fusion proteins. For example, U.S. Pat. No. 4,743,679 to Cohen et al. discloses the expression of epidermal growth factor (EGF) as a fusion protein with a leader sequence of up to 200 amino acids (preferably up to 75). The fusion protein is expressed in bacteria as an insoluble inclusion body.
U.S. Pat. No. 5,302,526 to Keck et al. is directed to recombinant DNA encoding amphophilic leader sequences (carrier segments) for the production and purification of fusion proteins. The polypeptide comprises an amphophilic helix designed to have hydrophilic charged amino acid residues on one side and nonpolar amino acid residues on the other side of the helix. When a gene encoding a protein of interest is attached to the helix, an inclusion body is formed. The inclusion bodies may be collected and purified.
U.S. Pat. No. 5,322,930 to Tarnowski et al. describes a method for expressing proteins as fusion proteins by using the portion of human pro-atrial natriuretic peptide (proATP) as the carrier for a heterologous peptide, wherein each of the Glu residues normally present in the proATP protein portion is altered to Gln.
U.S. Pat. No. 5,008,373 to Kingsman et al. describes a fusion protein system useful in vaccines or in diagnostic or purification applications. The fusion protein includes a first amino acid sequence derived from a retrotransposon or an RNA retrovirus encoded for by a yeast TYA gene sequence. The second amino acid sequence is a biologically active amino acid sequence, acting as the antigen.
U.S. Pat. No. 5,322,769 to Bolling, et al. is directed to a method for using CKS fusion proteins in assays.
Lin et al. (1987) disclose the use as an antigen of a fusion protein containing a carrier segment consisting of the gene 10 molecule of phage T7.
A major problem with prior art carrier segments is that the carrier segments also are known to be antigenic; that is, antibodies are produced in response to the carrier segment. Thus, there is a competition between the production of antibodies to the desired ligand and the production of antibodies to the carrier segment which may result in a lower production of antibodies with specificity for the target segment. Since the immune system usually reacts to surface exposed peptide segments which are often charged, it is likely that the existence of charged residues on the carrier segment exacerbates such problems with antigenicity.
Another problem with prior art carrier segments is that they often require the use of adjuvants. Adjuvants serve a variety of purposes (Klein, 1990). Adjuvants trap the antigen by causing the formation of an emulsion, precipitate or small vesicles at the injection site from which the antigen is released slowly over a prolonged period. The clearance of the antigen is thus delayed and the organism""s exposure to the antigen is lengthened. Adjuvants also stimulate the nonspecific migration of cells to the site of antigen injection and increase the probability of interaction of the antigen with cells of the immune system. Further, adjuvants increase antigen dispersion in the recipient""s body by continually delivering the antigen in small amounts from the injection site to the regional lymph nodes or spleen. Some adjuvants also have a mitogenic effect and so stimulate the proliferation of lymphocytes nonspecifically. Some adjuvants also help to stimulate lymphocytes by activating adenylate cyclase and other chemical messengers. Adjuvants may increase the probability of contact among T- and B-cells, macrophages, and antigens through the activation of lymphocyte-trapping mechanisms. The main problem with adjuvants is that some of the most effective ones tend to be toxic to and/or cause lesions in the host organism. They also can be difficult to handle.
The present invention is directed to a fusion protein carrier segment comprising a non-naturally occurring, hydrophobic, sparingly soluble amino acid sequence.
The present invention is also directed to a substantially nonantigenic fusion protein carrier segment comprising a non-naturally occurring, hydrophobic sparingly soluble amino acid sequence having a length at least about 65 amino acids long, wherein the carrier segment comprises no more than approximately 5% of the following amino acids arginine, lysine, aspartic acid, glutamic acid, cysteine, tryptophan and methionine.
The present invention further is directed to a carrier protein conjugate comprising a first amino acid sequence, wherein the first amino acid sequence is at least about 65 amino acids long and the first amino acid sequence lacks at least two of the following amino acids selected from the group consisting of the following negatively or positively charged side chains of amino acids: arginine, lysine, aspartic acid, glutamic acid; or uncharged side chains of the following amino acids: cysteine, tryptophan and methionine (with the exception of methionine at the amino terminal site); and a ligand fused to the first amino acid sequence.
Further, the present invention is directed to an amino acid sequence as illustrated in FIG. 1 [SEQ. ID. 1] or to an amino acid sequence as illustrated in FIG. 3 [SEQ. ID. 2].
The present invention also is directed to a non-naturally occurring fusion compound comprising an amino acid sequence as illustrated in FIG. 1 [SEQ. ID. 1] linked to a ligand.
The present invention also is directed to an expression vector comprising an amino acid sequence in a single reading frame with a coding sequence for an antigen, wherein the expression vector expresses a particle-forming fusion protein encoded by the amino acid sequence and a ligand, wherein the amino acid sequence is a non-naturally occurring, hydrophobic, sparingly soluble amino acid sequence wherein the amino acid sequence lacks at least two of the following amino acids selected from the group consisting of the following negatively or positively charged side chains of amino acids: arginine, lysine, aspartic acid, glutamic acid; or uncharged side chains of the following amino acids: cysteine, tryptophan and methionine (with the exception of methionine at the amino terminal site).
The present invention further is directed to an adjuvant for administering a high molecular weight protein to a host animal, the adjuvant comprising a non-naturally occurring, hydrophobic, sparingly soluble amino acid sequence.
The present invention also is directed to a process for producing an antibody to a ligand comprising: a) fusing a carrier segment comprising a non-naturally occurring hydrophobic sparingly soluble amino acid sequence to the ligand to form a fusion protein or carrier protein conjugate or carrier protein complex; b) presenting the antigen by in vivo or in vitro means; and c) producing the antibody to the ligand by in vivo or in vitro means.
The present invention also is directed to an assay for determining the concentration of an anti-antigen antibody in a test sample, wherein (a) at least a carrier protein conjugate is attached to a solid phase as capture reagent and is contacted with the test sample for a time and under conditions suitable for antigen/antibody of complexes to occur, and (b) an indicator reagent comprised of a signal generating compound and a specific binding member for the analyte is contacted with the complexes for time sufficient for a reaction to occur, wherein the signal generated is an indication of the presence of the anti-analyte antibody in the test sample. The improvement comprises attaching a fusion protein carrier segment comprising a non-naturally occurring hydrophobic sparingly soluble amino acid sequence to the solid phase as the capture reagent.
The present invention is further directed to a process for vaccinating a host vertebrate animal with an immunogen, comprising: (a) preparing an immunogen comprising a substantially nonantigenic fusion protein carrier segment containing a non-naturally occurring, hydrophobic, sparingly soluble amino acid sequence having a length at least about 65 amino acids long wherein the amino acid sequence lacks at least two of the following amino acids selected from the group consisting of the following negatively or positively charged side chains of amino acids: arginine, lysine, aspartic acid, glutamic acid; or uncharged side chains of the following amino acids: cysteine, tryptophan and methionine (with the exception of methionine at the amino terminal site); and (b) administering the carrier protein conjugate to the host vertebrate animal.
The present invention also is directed to a process for vaccinating a host vertebrate animal with an immunogen, comprising: (a) forming an immunogen comprising a non-naturally occurring carrier protein conjugate containing an amino acid sequence as illustrated in FIG. 1 [SEQ. ID. 1] and a ligand fused to the amino acid sequence; and (b) administering the carrier protein conjugate to the host vertebrate animal.
Further, the present invention is directed to a process for immunopurifying antibodies from a pool of antibody material, comprising: (a) forming a substantially nonantigenic fusion protein carrier segment containing a non-naturally occurring, hydrophobic, sparingly soluble amino acid sequence having a length at least about 65 amino acids long wherein the amino acid sequence lacks at least two of the following amino acids selected from the group consisting of the following negatively or positively charged side chains of amino acids: arginine, lysine, aspartic acid, glutamic acid; or uncharged side chains of the following amino acids: cysteine, tryptophan and methionine (with the exception of methionine at the amino terminal site); (b) incubating the antibody material with the carrier protein conjugate under binding conditions to bind the antibody material to the carrier protein conjugate to form an antibody/conjugate complex; (c) separating out the antibody/conjugate complex; (d) dissociating the antibody from the antibody/conjugate complex; and (e) separating the antibody from the antibody/conjugate complex.
Further, the present invention is directed to a process for producing peptides, comprising: (a) incubating a fusion protein containing a fusion protein carrier segment comprising a non-naturally occurring hydrophobic sparingly soluble amino acid sequence, wherein the amino acid sequence lacks at least two of the following amino acids selected from the group consisting of the following negatively or positively charged side chains of amino acids: arginine, lysine, aspartic acid, glutamic acid; or uncharged side chains of the following amino acids: cysteine, tryptophan and methionine (with the exception of methionine at the amino terminal site), under conditions where the peptide bonds on the fusion protein are cleaved; and (b) separating out the desired peptides.
Further, the present invention is directed to a protease inhibitor comprising a fusion protein containing a fusion protein carrier segment comprising a non-naturally occurring hydrophobic sparingly soluble amino acid sequence and a cleavage site for a protease, wherein the fusion protein is isolated and used as a competitive inhibitory substrate.
Further still, the present invention is directed to a solid support having absorbed thereon a carrier protein conjugate comprising: (a) a first amino acid carrier sequence, wherein the first amino acid sequence is at least about 65 amino acids long and the amino acid sequence lacks at least two of the following amino acids selected from the group consisting of the following negatively or positively charged side chains of amino acids: arginine, lysine, aspartic acid, glutamic acid; or uncharged side chains of the following amino acids: cysteine, tryptophan and methionine (with the exception of methionine at the amino terminal site); and (b) a ligand fused to the first amino acid carrier sequence.
The present invention also is directed to an assay for determining the concentration of an enzyme in a test sample, wherein (a) at least a carrier protein conjugate containing a ligand upon which the enzyme can act is attached to a solid phase and is contacted with the test sample for a time and under conditions suitable for the enzyme to act upon the substrate, and (b) indicator reagents capable of generating a signal change in response to the enzyme-catalyzed modification of the immobilized substrate is contacted with the complexes for time sufficient for a reaction to occur, wherein the signal generated is an indication of the presence of the enzyme in the test sample. The improvement comprises attaching a recombinant fusion protein carrier segment comprising a non-naturally occurring hydrophobic sparingly soluble amino acid sequence to the solid phase as the capture reagent.
The present invention also is directed to a test kit for use in detecting the presence of anti-antigen antibodies in a test sample, which test kit contains a container containing at least one protein specific for the anti-antigen antibody and, wherein the improvement comprises a container containing a non-naturally occurring hydrophobic sparingly soluble amino acid sequence, which is specific for the anti-antigen antibody.
The present invention also is directed to an immunoassay kit for detecting a specific antigen, comprising in separate containers:
a. a solid support having bound thereto one or more antibodies produced according to the process described above that will specifically react with a desired antigen;
b. a buffer to remove unbound proteins;
c. solutions for detection of bound analyte; and
d. instructions for use.
The advantages of the present invention are specifically directed to the novel carrier segment. Some of the advantages of the carrier segment are as follows:
Low Antigenicity: One of the primary goals of the present invention is to make antibodies to a ligand. In order to have the best opportunity to make the antibodies to the ligand, the carrier segment portion of the fusion protein must be relatively nonantigenic to the animal. Typically, the immune system in a host body will target foreign materials, i.e., antigens presented to the system. When an antigen such as a fusion protein enters the body, the immune system will seek out the most antigenic moiety to attack. If the carrier segment happens to contain the most notable antigen, the immune system will preferentially target the carrier segment and have little response to the target ligand segment of choice. This is often the case primarily because the carrier segment tends to be the larger segment, usually 300 or more amino acids. In naturally occurring proteins used as carrier segments, there are also a large number of charged amino acids.
Charged amino acid sequences are more likely to be surface-exposed and antigenic than are hydrophobic amino acid sequences. Thus, the carrier segment has more potential epitopes, and consists of residues which frequently are more easily recognized as foreign or dangerous by the immune system. By making the carrier segment small and very low in antigenicity, the immune system will be more likely to attack the ligand and produce antibodies to the ligand.
For the purposes of the present invention, low antigenicity is defined as failure of the carrier segment to induce formation of greater than 50% of the specific antibody generated in response to three or more injections into chickens, mice and rabbits of a fusion protein consisting of the carrier segment fused to a ligand having the sequence: H2N-Lys Met Ala Glu Asp Asp Pro Tyr Leu Gly Arg Pro Glu Gln Met [SEQ. ID. 4]
One way of reducing the antigenicity of the carrier segment is to reduce its size. This allows the attached ligand to comprise a significantly greater fraction of the total fusion protein. Typically, the carrier segment contains between approximately 200 and 500 amino acids in length. However, by reducing the length of the segment to an amino acid length of approximately 100 or fewer amino acids and removing many charged amino acids, the carrier segment is less effectively displayed to the immune response in the host organism. The carrier segment should be at least 65 amino acids long, and preferably 100 amino acids long. At the very least, the length of the carrier peptide should be sufficiently long to allow effective expression within the procaryotic host expression organism.
Low Solubility: A major advantage of the present carrier segment is that it is sparingly or slowly soluble. This results in an advantage for rapid purification since injection quality immunogen containing low levels of pyrogen can be prepared using simple washes as opposed to conventional methods such as chromatography, thus resulting in savings in both time and equipment. Additionally, the sequestration of the peptides in inclusion bodies when expressed may protect labile sequences from proteolytic attack.
No Need for Adjuvants: An additional advantage of the carrier segment is that it may act as its own adjuvant as well as a conventional carrier protein due to various properties of the carrier segment and of conjugates containing the segment, including low solubility and mitogenic effects.
A typical way researchers currently prepare antigens for production of antibodies is to chemically synthesize the ligand or peptide using techniques known to the art, and then to chemically crosslink it to a larger protein, known as a carrier protein. The function of the carrier protein is to elicit T-cell help. T-cell help is important in producing an effective antibody response within an animal. However, many ligands and peptides are too small to both present the desired antigenic site and to include a segment which allows the material to elicit T-cell help. Certain proteins, such as keyhole limpet hemocyanin, are known to the art to contain effective sites for eliciting T-cell help, and are thus often coupled to small ligands for this purpose. Unfortunately, as discussed previously, many of these also are antigenic and can dominate the antibody response. The carrier segment described elicits the necessary T-cell help without dominating the antibody response, and thus is a superior carrier protein.
A typical way researchers currently prepare a dosage of the antigen for injection for the production of antibodies is to formulate it in any number of suspension, precipitate or emulsion forms, called adjuvants. Adjuvants can augment the immune response as the result of the combined effect of several factors. If the antigen were injected into the host animal as is, it would be in a soluble form and would be quickly dispersed from the site of injection and cleared from the body Since the immune system needs time to recruit immune cells to the site of injection and to mount a response, the quick dispersal and clearance of antigen is detrimental to the immune response. Formulation of the antigen so that it is trapped at the site of injection is an effort to keep the antigen localized long enough for the immune system to locate it and mount a response. In most cases, the antigen is not trapped long enough at the site to elicit a robust immune response, so multiple injections over a period of several weeks are required. Additionally, recruitment of immune cells to the site of injection usually requires some local nonspecific inflammation. For this reason, some adjuvant formulations also contain an irritant for this purpose. Adjuvants also may trap the recruited immune cells, thereby enhancing the interactions of the immune cells. Finally, adjuvants may stimulate proliferation of the immune cells.
The low solubility of the carrier segment and of conjugates containing it creates conditions at the injection site that are sufficient for mounting an immune response; namely, that some sort of nonspecific inflammatory response is created that recruits immune cells to the location, that antigen is sequestered at the site long enough for an immune response to be mounted, that interactions between the immune cells may be potentiated, and that immune cell proliferation is stimulated. If the solubility were too low, or if the antigen were not accessible to the immune system, no response would be achieved; thus, the solubility of the carrier segment is thought to be in an optimal range which balances the need for sequestration against the requirement for slight solubility and effective antigen display. Thus, the carrier segment has been designed to provide all functions required for eliciting an immune response; recruitment of immune cells to the injection site, sequestration of antigen at the site, eliciting T-cell help without dominating the antibody response, and effective antigen display to the immune system. The advantages of this system over prior art is that it eliminates the need for a step involving coupling to a carrier protein, and a step involving formulation in an adjuvant. Additionally, a single injection of antigen is sufficient to elicit an ample immune response.
Most adjuvants induce the formation of granulomas in animals and humans. For this reason, most adjuvants are not allowed for use in humans although they are allowed for use in animals (Klein, 1990). Therefore, a system which does not require the use of adjuvants is not only more humane, but may have significant benefits specifically in the field of vaccine development.
Using the carrier segment described, antibody isotype response may be able to be altered. Different isotypes or classes of antibody heavy chains are known to have unequal effector functions, such as the capacity to fix complement, and unequal capacity to bind available affinity resins, such as Protein A. Thus, antibodies with the same antigen specificity but of a different isotype have disparate effector functions and resin-binding affinities. The system of the present invention induces different antibody isotype profiles in response to different concentrations of the antigen. This suggests that a system may be developed which will allow the regulation of the predominant isotype or class of the antibodies which are made using this technology.
Excellent Expression: The property of excellent expression simplifies the production of a fusion protein by allowing small fermentations to be performed for the isolation of sufficient antigens for immunizations as well as subsequent uses such as validation assays and affinity purification regimens. It is logical to assume that enough of the fusion protein must be made in order for it to be injected into the host animal for antibody production. Usually, research requires the injection of more than one host animal. The carrier segment of the present invention is advantageous in that it is able to be expressed at a very high rate, e.g., xe2x89xa75 mg/l in standard culture medium, in bacteria. Another advantage is that it allows the accumulation of the peptide without rapid degradation, thus allowing intact fusion proteins to be isolated.
Works with a Variety of Target Ligands: Another advantage of the carrier segment of the present invention is that it is relatively nonspecific in terms of attaching to target ligands. Therefore, virtually any type of ligand can be fused to the nonantigenic, sparingly soluble carrier segment to produce a useful immunogen in which the carrier segment is nonantigenic and the desired peptide is selectively displayed to the immune system.
Broad Utility as an Antigen: Another advantage of the present invention is that the fusion protein created by the carrier segment of the present invention creates enhanced antigenic responses in most antibody producing species. Typical species include vertebrates such as the mouse, rat, rabbit, chicken, goat, sheep, donkey, horse and human. The fusion protein has been shown to be effective using a variety of routes of injection as discussed infra.
Yield of Specific Antibodies Can be High: Another advantage of the present invention is that the ratio of specific antibodies to the ligand of interest compared to those antibodies directed against the carrier segment of the fusion conjugate is high. Typical carriers, such as KLH or BSA, are both antigenic in nature and much larger in size than the ligand. Thus, many or most of the antibodies produced in response to immunization with such a compound are directed against the carrier segment.
The present invention constitutes a much smaller carrier segment which has low antigenicity. Since there are both fewer epitopes and less antigenic epitopes presented to the immune system with the current invention, there is a net effect of making the ligand immunodominant. This results in a more robust immune response to the ligand of interest.
Production of Peptides: The present invention also advantageously allows the rapid production of large quantities of short peptides of defined sequences to be expressed as an insoluble fusion protein. The hydrophobic carrier segment can be cleaved and removed, or left attached. In addition to the uses listed above, leaving the carrier segment attached enables the peptide to be immobilized on hydrophobic surfaces, which may have utility for a wide variety of applications. The peptides can be used in all ways other short peptides are used, such as the neutralization of antibodies, direct immunization as discussed above, conjugation to other carriers for immunization, epitope mapping, as therapeutic agents, substrates for the assays of enzymes, and other applications. As is well-known in the prior art, fusion proteins can be processed by a variety of reagents to yield the desired peptide sequence separated from the carrier segment. An advantage of this invention is that removal of the carrier segment is facilitated by the low solubility of the carrier segment when the desired peptide is cleaved off.
Other advantages of the present invention over conventional peptide synthesis include lower cost of production of small quantities of peptides of defined sequences. Further, no toxic reagents are required in the process of the present invention. There also is less of a chance of modification of amino acid side chains, which has been demonstrated to be a problem with conventionally synthesized peptides.
The present invention also offers significant improvements over the current technology for making antibodies to peptides or proteins. The present invention makes it easier for an antibody to be made from a peptide sequence of a protein without requiring knowledge of the entire sequence of the target protein, as well as making antibodies with high affinity, specificity, and avidity to both the peptide and the parent protein from which the peptide was derived. Therefore, the basic problems involved with immunization, immunoaffinity purification of antibodies from polyclonal sera, peptide production and epitope mapping or identification can all be accomplished in facile, inexpensive, safe ways using equipment and methods very familiar to biologists not accustomed to working with peptides or synthesizing peptides.
The product of the present invention is designed to 1) produce a safe vaccine against infectious diseases, and 2) synthesize defined proteins against which antibodies can be raised for experimental, industrial, pharmaceutical and diagnostic purposes.
The present invention also is useful in the production of diagnostic reagents for use in diagnostic assays. The fusion protein, comprising the combination of carrier sequence and ligand, can be dispersed or immobilized on a variety of solid supports such as test tubes, microliter plate wells, dipsticks and the like. Moreover, using this technology makes it possible to generate longer peptides than feasible under standard chemical synthetic methods.
These and other aspects of the present invention will become evident upon reference to the following detailed description of the invention, the examples, and the attached drawings and photographs.

High level expression and facile purification of proteins, peptides and conjugates for immunization, purification and detection applications


Provided are methods for producing a thermoplastic vulcanizate and thermoplastic vulcanizates provided therein. The method includes introducing vulcanizable rubber, thermoplastic resin, a masterbatch of a propylene-based elastomer and a cure accelerator for a phenolic resin curative to the reactor, and phenolic resin curative to a reactor and dynamically vulcanizing the rubber with the phenolic resin curative in the presence of the cure accelerator and the thermoplastic resin.

Thermoplastic vulcanizates ("TPVs") comprise blends of dynamically cured rubbers and thermoplastic resins where the rubber is dispersed within the thermoplastic resin phase as finely-divided rubber particles. TPVs have advantageously demonstrated many of the properties of thermoset elastomers, yet are processable as thermoplastics. As such, elastomeric articles are often extruded from TPVs using thermoplastic extruding techniques.
TPVs have been prepared by dynamically vulcanizing the rubber in the presence of a curative, such as a phenolic resin, while the rubber is being mixed with a thermoplastic resin. Often cure accelerators or activators are used to aid in the vulcanization process. For example, U.S. Pat. No. 4,311,628 illustrates TPVs that are produced using phenolic resin cure systems that include a phenolic curing resin and a cure accelerator, such as stannous chloride.
Stannous chloride is a solid material and is supplied in the form of a powder. The powder can be difficult to handle and is not easily metered into the reactors where dynamic vulcanization takes place. For example, powdered stannous chloride is hygroscopic and has a tendency to compact and clump if exposed to moisture in the air. Further compaction can occur within the feeder which can result in inconsistent addition of the stannous chloride to the extruder and fouling or plugging of the feeder. In such cases, removal of blockages within the feeder may result in stoppage of the TPV production line or may require a new feeder. Additionally, the powdered stannous chloride can be difficult to disperse throughout the blend of the rubber and thermoplastic resin. Uneven dispersion of the stannous chloride into the TPV production process can affect the cross-linking of the rubber phase during vulcanization.
There is a need for methods of making TPVs that minimize or eliminate issues arising from the addition of powdered cure accelerators, and a method which increases the consistency of the addition of cure accelerators to the vulcanization process. There is also a need to provide methods of making TPVs that have more consistent cure.
GB Patent Nos. 2455981 B1 and 2489123 B1, GB Patent Application Publication No. 2510930, and GB Patent Application No. 1312608, describe masterbatches of stannous chloride and polypropylene.
PCT Publication No. WO 2011/081746 has attempted to overcome some of these difficulties by supplying the stannous chloride to the vulcanization process as a masterbatch with polypropylene. However, there can still be uneven dispersion of the stannous chloride within the rubber phase.

Process for forming thermoplastic vulcanizates and thermoplastic vulcanizates made therefrom


A digital/analogue TV receiver having a function for displaying an EGP screen comprises a controller for displaying the EPG (electric program guide) screen including channels and TV program information on a display apparatus, and a memory for storing a channel map memorizing the TV program information correspondingly to the channels. The controller renews the channel map stored in the memory with using VCT (virtual channel table) information and EIT (event information table) information which are delivered with the TV broadcasting signals while image signals of a TV program is outputted to the display apparatus. The controller uses the TV program information memorized in the channel map stored in the memory when the EPG screen is displayed on the display apparatus.

1. Field of the Invention
The present invention relates to a digital/analogue TV (television) receiver having an EPG (electric program guide) screen display function, by which electric information of TV programs delivered within TV broadcasting signals are extracted and the EPG screen including TV program guide such as channels and contents of the TV programs are displayed.
2. Description of the Related Art
In recent years, digital TV broadcast is quickly popularized owing to progression of digital technology. In the digital TV broadcast, a plurality of TV programs is delivered in a single frequency band. Image signals and sound signals of the TV programs are encoded by compression owing to digital data compression technology, and the encoded signals are time shared and multiplexed. Subsequently, the time shared and multiplexed signals are modulated to high frequency radio waves in a predetermined frequency band, and delivered as the TV broadcasting signals. In the digital TV broadcast, the electric information of the TV programs including the channel information of the TV programs are delivered with the image signals and the sound signals of the TV programs at a predetermined interval by time sharing and multiplexing them.
In the digital TV broadcast, the TV broadcasting signals in the predetermined frequency band, which is formed by time sharing and multiplexing a plurality of TV broadcasting signals of the TV programs, is called "physical channel", and each TV broadcasting signal of the TV program, which is to be multiplexed in the frequency band, is called "sub-channel".
In a TV receiver for receiving the digital TV broadcasting signals, when a user selects a channel (physical channel and sub-channel) of a TV program which he wishes to see by operating a channel changer, the high frequency radio waves in the predetermined frequency band corresponding to the physical channel are received. By decoding the received radio waves, a signal called "transport stream signal" can be obtained, in which the encoded image signals and sound signals of the TV programs and the electric information of the TV programs are time shared and multiplexed.
The TV receiver extracts and separates the image signal and the sound signal of the TV program corresponding to the sub-channel from the transport stream signal. Subsequently, the TV receiver decodes the image signal and the sound signal to the states of them before the compression, and outputs the decoded image signal and sound signal to a display apparatus. The TV receiver further has a function to extract the electric information of the TV programs from the transport stream signal, to form the electric program guide (EPG) consisting of titles, channels, broadcast times and so on of the TV programs, and to display the EPG screen on the display apparatus. The displaying of the EPG screen on the display apparatus is selected by operating the channel changer.
In North America, the digital TV broadcast called ATSC (advanced television system committee) is delivered. The ATSC broadcast delivers information called PSIP (program and system information protocol) including various data with respect to the TV broadcast multiplexed with the image signals and the sound signals of the TV programs on air in each physical channel. The PSIP further includes electric information of TV programs called VCT (virtual cannel table) and EIT (event information table).
The VCT relates to information showing a relation between a cannel number and a source ID of a TV program on air, which includes channel number information and a source ID corresponding to a sub-channel of the TV program on air. The EIT relates to information showing a relation between TV program information and a source ID of a TV program on air or scheduled, which includes TV program information such as a title, start and end times of the TV program and the source ID.
In the conventional TV receiver for receiving the ATSC broadcast, when the user selects to display the EPG screen by operating the channel changer, an EPG screen 70, for example, shown in FIG. 9 is displayed on the display apparatus. On the EPG screen 70, a plurality of channel grids 71 shows channel numbers of the TV programs, and a plurality of program grids 72 disposed at right side of the channel grids 71 shows titles of the TV programs which will be come on the air on the channel. Start times of the TV programs are shown above the program grids 72. On the EPG screen 70, the TV programs are shown correspondingly to the channels and the start times.
The EPG screen 70 can be scrolled above and below by operating the channel changer so as to show other channels. In FIG. 9, the channel grids 71 corresponds to the channels 34-1 to 50-2. When any one of the channel grids 71 is selected by operating the channel changer, the TV broadcasting signals corresponding to the selected channel is tuned, so that an image of a TV program on the channel is appeared on the display apparatus. When an EXIT grid 76 of the EPG screen 70 is selected, the EPG screen is disappeared.
For showing the RPG screen 70, it is necessary that the titles and the start times of the TV programs are corresponded to the channels. As mentioned above, the EIT includes the TV program information such as the title and the start and end times of the TV program and the source ID, but includes no channel number information. On the other hand, the VCT includes the channel number information and the source ID corresponding to the TV program, but includes no TV program information such as the title and the start and end times. Thus, the correspondence of the title and the start time of the TV program with the channel is based on the source ID commonly included in the EIT and the VCT.
A conventional apparatus, for example, shown in Publication Gazette of Japanese Patent Application 2001-86425 takes a table including the channel number information and a table including event information, and supplies a channel list corresponding to the time of the events to the users, with respect to displaying the TV program information of the digital TV broadcast. Another apparatus, for example, shown in Publication Gazette of Japanese Patent Application 2001-136495 can display the information of local events in the EPG of the digital TV broadcast in detail, and can store and transmit the program data.
In the above-mentioned conventional TV receivers, the TV broadcasting signals of all the physical cannels are serially tuned and received, after the operation for displaying the EPG screen. Subsequently, the VCTs and the EITs are extracted from the TV broadcasting signals of each physical channel, and the titles and the start times of the TV programs are corresponded to the channels with using the source IDs commonly included in the EITs and the VCTs. Therefore, it takes a long time after operating the EPG screen displaying for forming and displaying the completed EPG screen on which the TV program information with respect to all of the physical channels are shown.
Furthermore, when the operation for displaying the EPG screen is started, another operation such as for selecting the TV channel cannot be operated until the EPG screen is displayed. Thus, the user has no alternative but to wait until the EPG screen is displayed, so that the user feels annoyance or discomfort. Such the disadvantage cannot be solved even when the technologies shown in the above-mentioned publication gazettes are applied.

Digital/analogue TV receiver that renews a channel map using event information and virtual channel tables


A grounds maintenance system comprising: a robot tractor comprising; a robot body; a drive system including one or more motorized drive wheels to propel the robot body; a control system coupled to the drive system, the control system configurable to store a mow plan that specifies a set of paths to be traversed for a grounds maintenance operation and control the drive system to autonomously traverse the set of paths to implement the mow plan; a battery system comprising one or more batteries housed in the robot body; and a low-profile mowing deck coupled to the robot body, the mowing deck adapted to tilt and lift relative to the robot body, wherein the control system is configured to control tilting and lifting of the mowing deck and cutting by the mowing deck.

Renewable energy is becoming a larger and larger component of energy production across the world. Renewable energy farms are typically located on large plots of lands, often in rural or remote areas. In general, it is desirable to have substantial ground cover on renewable energy farms, both for aesthetic reasons and to resist ground erosion. With ground cover, however, comes the attendant problem of managing vegetation. Improper maintenance of the grounds can lead to overgrown vegetation, weed infestations, reduced production, unsafe working conditions and increased fire risk.
With the advent of industrial mowers, it has become easier to maintain large areas of real estate. However, the use of such mowers still represents a large investment in human capital. Moreover, the variable nature of such maintenance remains hard to predict. Consequently, the need for grounds maintenance retards the growth of renewable energy.

System and method for automated grounds maintenance


A receiver receives payload data from a downstream signal, and includes a filter to receive the downstream signal, and including signalling data identifying downstream resources for the payload data, and an analog to digital converter to receive the downstream signal from the filter and to convert it into a sampled digital form. A demodulator demodulates the digital form of the downstream signal to recover the payload data and the signalling data. The signalling data includes a mode switch signal to indicate an active mode or a sleep mode for the receiver. A controller detects the mode switch signal to control the analog to digital converter to switch sampling rates in response thereto, and to control the filter to switch frequency bands. The frequency bands perform anti-alias filtering for respective sampling rates.

There are various media via which data can be communicated including terrestrial and satellite radio frequency signals for both broadcast systems and cellular mobile communication systems where mobile terminals communicate using radio signals to a network of base stations. Another media for communicating data is a cable network which can be a coaxial cable or optical fibre in which data is modulated and communicated through the cable. Cable systems can be used to form broadcast systems in which a Cable Modem Termination System (CMTS) or head end modulates data onto signals for transmission through the cable network to a receiver which is known as a Cable Modem (CM). An example of a cable modem system which has been developed for communicating data including television signals via a cable network is the Data Over Cable Service Interface Specifications (DOCSIS) system which is administered by CableLabs. DOCSIS 3.0 for example provides a physical layer and a media access layer specification for arranging for data to be communicated via a cable network. The specification provides various communication techniques between the CMTS and the CMs for efficiently using an available bandwidth within the cable network.
One improvement which can be made to CMs is to reduce power consumption particularly for example when there is no payload data being transmitted to the CM by the CMTS.


Embodiments provide a service request processing method, a related device, and a communications system in an IMS network. In some embodiments, because 5GC network slices correspond to different services, P-CSCFs in the IMS also correspond to different service information. After receiving a terminated service request sent by an I-CSCF, a first S-CSCF can obtain an address of a corresponding P-CSCF based on terminated service information carried in the terminated service request. Then, the first S-CSCF sends the terminated service request to the P-CSCF corresponding to the address, and the P-CSCF processes the terminated service request.

A 5th generation (5G) network is a next-generation network to be deployed as expected by a network operator, and features a high rate and a low latency. Network slicing (slice) is one of features provided by the 5G network, and can meet different service requirements by slicing the 5G network into different network slices. User equipment (UE) can select corresponding 5G core network slices (5GC slices) based on different service requirements, and initiate different services.
A service-call session control function (S-CSCF) device in an IP multimedia subsystem (IMS) network is mainly configured to receive a terminated service request for the UE and then route the terminated service request to a proxy-call session control function (P-CSCF) device, in an IMS network, with which the UE currently registers. Further, the P-CSCF can send the terminated service request to the UE for processing.
However, when accessing the IMS network through different 5GC network slices, the UE performs a plurality of times of registration in the IMS network through different P-CSCFs, and each time of registration corresponds to one 5GC network slice. After the registration succeeds, a user can initiate different IMS services in the different 5GC network slices. However, the prior art does not resolve a technical problem of how the S-CSCF in the IMS sends a terminated service request for the UE to a corresponding P-CSCF for processing after the UE accesses the IMS through the different 5GC network slices.

Service request processing method, apparatus, and communications system


A catalytic element for promoting crystallization of an amorphous silicon film is efficiently gettered to provide a highly reliable TFT, and an electro-optical device using the TFT and a method of manufacturing the electro-optical device are provided. The electro-optical device has an n-channel TFT and a p-channel TFT. A semiconductor layer of the p-channel TFT has a channel forming region (13), a region (11) containing an n-type impurity element and a p-type impurity element, and a region (12) containing only a p-type impurity element. In the p-channel TFT, a wiring line for electrically connecting the TFTs is connected to the region (12) containing only a p-type impurity element. The region containing an n-type impurity element in the p-channel TFT is narrower than a region doped with an n-type impurity element in a semiconductor layer of the n-channel TFT.

1. Field of the Invention
The present invention relates to an electro-optical device (semiconductor device) including a circuit that is composed of a thin film transistor (hereinafter referred to as TFT) formed on an insulator, and to a method of manufacturing the same. Specifically, the present invention relates to an electro-optical device (semiconductor device) represented by a liquid crystal display device in which a pixel portion and a driving circuit provided in the periphery of the pixel portion are formed on the same substrate, and to an electronic appliance using the electro-optical device (semiconductor device) as a display unit.
2. Description of the Related Art
In recent years, a large number of TFTs have been developed which use as an active layer a polycrystalline semiconductor film obtained by crystallizing an amorphous semiconductor film that is formed on an insulating substrate such as a glass substrate. In particular, polysilicon films or other crystalline silicon films obtained by crystallizing an amorphous silicon film are often employed.
A process of forming a large-area polysilicon film on a substrate that has a low resistivity against heat, such as a glass substrate and a plastic substrate, is also a research and development theme that continues to attract researchers. Crystallization using laser light and crystallization involving doping with a crystallization-promoting catalytic element and heat treatment are given as examples of a so-called low temperature crystallization technique.
One of the latter crystallization techniques, in which an amorphous silicon film is doped with a catalytic element for promoting crystallization and then subjected to heat treatment to be crystallized, is disclosed in Japanese Patent Application Laid-open No. Hei 7-130652.
According to this technique, the temperature required to crystallize an amorphous silicon film can be lowered by 50 to 100xc2x0 C. and time required for crystallization is shortened to ⅕ to {fraction (1/10)} as well with the effect of a catalytic element. The technique thus makes it possible to form a crystalline silicon film having a large surface area on a substrate of low heat resistance as those mentioned above. Also, it is a confirmed fact that a crystalline silicon film obtained by this technique has an excellent crystallinity.
The above crystallization technique using a catalytic element employs a metal element such as Ni and Co for the catalytic element. These metal elements generate a great energy level in the silicon film to trap carriers and cause recombination of the carriers. Therefore, when the obtained crystalline silicon film is used to form a TFT, it is expected that the electric characteristic and the reliability of the TFT are affected.
In addition, the catalytic element remaining in the silicon film has been observed to segregate irregularly. The catalytic element segregates most in crystal grain boundaries, and it is considered that this segregation provides a leak path for a small amount of current and causes an abrupt increase in OFF current (a current flowing in a TFT when the TFT is in an OFF state).
For that reason, the catalytic element has to be quickly removed, or reduced to a degree that it does not exert any electric influence, once the crystallization step is finished. A technique that utilizes the gettering effect can be used to remove or reduce the catalytic element.
One of existing gettering methods includes the steps of partially covering, with a resist mask, a crystalline silicon film obtained by crystallizing an amorphous silicon film with the help of a metal element so as to cover a portion of the crystalline silicon film that is to serve as a channel forming region in a semiconductor layer of a TFT, and doping the rest of the semiconductor layer of the TFT with P or other Group 15 elements effective in gettering in high concentration to form a region that promotes gettering (the region is hereinafter called a gettering sink). Another example of the existing gettering methods involves similarly covering the region of the crystalline silicon film that serves as the channel forming region of the TFT with a resist mask and forming a gettering sink containing P or other Group 15 elements in high concentration in the periphery of a portion of the crystalline silicon film that forms the semiconductor layer of the TFT. However, these methods need the mask formation step, thereby resulting in increases in the number of masks and the number of manufacturing steps. Therefore, the methods have problems in productivity, yield, and manufacturing cost.
Further, when a p-channel TFT is formed, a region for forming the p-channel TFT is doped with a p-type impurity element (boron (B), in this example) to form a source region and a drain region after doped with a large amount of phosphorus for gettering. In order to invert the n-type conductivity of the region for forming the p-channel TFT, which has been given by phosphorus (P) through the previous doping, the region has to be doped with boron (B) in considerably high concentration.
This brings a problem of reduced throughput in the doping step, or a problem of difficulty in improving the crystallinity of the source region and the drain region by heat treatment.
The semiconductor layer has to be doped with phosphorus (P) in order to carry out the gettering treatment. However, doping with a p-type impurity element (typically, boron (B)) is also needed to form a p-channel TFT. Since the step of doping with an n-type impurity element (phosphorus (P)) precedes the step of doping the semiconductor layer of the p-channel TFT with boron (B), the layer has to be doped with the p-type impurity element in a concentration high enough to invert the n-type conductivity to the p-type conductivity (called counter doping or cross doping). The concentration of boron (B) in the layer has to be higher than the concentration of phosphorus (P) with which the layer has previously been doped. However, if the concentration of the impurity element is too high, the resistivity of the source drain region is raised to lower ON current. Counter doping is also unsatisfactory in terms of manufacture cost and productivity because it requires excessive ions as acceptors for doping.
The present invention has been made in view of the above, and an object of the present invention is therefore to provide a highly reliable electro-optical device and a method of manufacturing the electro-optical device by efficiently gettering a catalytic element used to promote crystallization of an amorphous silicon film.
One of the features of the presnet invention is an electric device comprising a semiconductor layer on an insulator, a gate insulating film on the semiconductor layer, and a gate electrode on the gate insulating film, wherein the electric device has an n-channel TFT and a p-channel TFT, wherein the semiconductor layer in the p-channel TFT includes a channel forming region (13), a region (11) containing an n-type impurity element and a p-type impurity element, and a region (12) containing only a p-type impurity element, and wherein a wiring line for electrically connecting the TFTs to one another is connected to the region (12) containing only a p-type impurity element in the p-channel TFT.
Another one of the features of the presnet invention is an electric device comprising a semiconductor layer on an insulator, a gate insulating film on the semiconductor layer, and a gate electrode on the gate insulating film, wherein the electric device has an n-channel TFT and a p-channel TFT, wherein the semiconductor layer in the p-channel TFT includes a channel forming region (13), a region (21a, 21b) containing an n-type impurity element and a p-type impurity element, and a region (22) containing only a p-type impurity element, wherein the region (22) containing only a p-type impurity element is sandwiched between the region (21a) containing an n-type impurity element and a p-type impurity element and the region (21b) containing an n-type impurity element and a p-type impurity element, and wherein a wiring line for electrically connecting the TFTs to one another is connected to the region (12) containing only a p-type impurity element in the p-channel TFT.
In the above electric device, wherein the gate electrode is a single layer or a laminate formed of elements selected from the group consisting of Ta, W, Ti, Mo, Al, and Cu, or of alloy materials or compound materials mainly containing these elements.
One of the features of the presnet invention is a method of manufacturing an electrice device, comprising: forming an amorphous semiconductor layer on an insulator; doping the amorphous semiconductor layer with a catalytic element for promoting crystallization; heating the amorphous semiconductor layer doped with the catalytic element to obtain a crystalline semiconductor layer; forming a gate insulating film on the crystalline semiconductor layer; forming a conductive film on the gate insulating film and etching the conductive film to form a gate electrode of an n-channel TFT and to form in a p-channel TFT a conductive layer that is to serve as a gate electrode; doping the semiconductor layer with an n-type impurity element while using the gate electrode and the conductive layer as masks; and etching the conductive layer to form a gate electrode of the p-channel TFT while covering a region that is used for the n-channel TFT with a resist mask, and then doping the semiconductor layer in the p-channel TFT with a p-type impurity element.
One of the features of the presnet invention is a method of manufacturing an electrice device, comprising: forming an amorphous semiconductor layer on an insulator; doping the amorphous semiconductor layer with a catalytic element for promoting crystallization; heating the amorphous semiconductor layer doped with the catalytic element and then irradiating the semiconductor layer with a laser to obtain a crystalline semiconductor layer; forming a gate insulating film on the crystalline semiconductor layer; forming a conductive film on the gate insulating film and etching the conductive film to form a gate electrode of an n-channel TFT and to form in a p-channel TFT a conductive layer that is to serve as a gate electrode; doping the semiconductor layer with an n-type impurity element while using the gate electrode and the conductive layer as masks; and etching the conductive layer to form a gate electrode of the p-channel TFT while covering a region that is used for the n-channel TFT with a resist mask, and then doping the semiconductor layer in the p-channel TFT with a p-type impurity element.
One of the features of the presnet invention is a method of manufacturing an electrice device, comprising: forming an amorphous semiconductor layer on an insulator; doping the amorphous semiconductor layer with a catalytic element for promoting crystallization; heating the amorphous semiconductor layer doped with the catalytic element to obtain a crystalline semiconductor layer; forming a gate insulating film on the crystalline semiconductor layer; forming a conductive film (A) and a conductive film (B) on the gate insulating film; etching the conductive film (A) and the conductive film (B) to form first shape gate electrodes; doping the semiconductor layer with an n-type impurity element while using the first shape gate electrodes as masks; etching the first shape gate electrodes to form second shape gate electrodes narrower than the first shape gate electrodes; doping the semiconductor layer with an n-type impurity element while using as masks the second shape gate electrodes; etching the second shape gate electrodes to form third shape gate electrodes; etching the third shape gate electrodes to form fourth shape gate electrodes; and doping the semiconductor layer in the p-channel TFT with a p-type impurity element while using the fourth shape gate electrodes as masks.
One of the features of the presnet invention is a method of manufacturing an electrice device, comprising: forming an amorphous semiconductor layer on an insulator; doping the amorphous semiconductor layer with a catalytic element for promoting crystallization; heating the amorphous semiconductor layer doped with the catalytic element and then irradiating the amorphous semiconductor layer with a laser to obtain a crystalline semiconductor layer; forming a gate insulating film on the crystalline semiconductor layer; forming a conductive film (A) and a conductive film (B) on the gate insulating film; etching the conductive film (A) and the conductive film (B) to form first shape gate electrodes; doping the semiconductor layer with an n-type impurity element while using the first shape gate electrodes as masks; etching the first shape gate electrodes to form second shape gate electrodes narrower than the first shape gate electrodes; doping the semiconductor layer with an n-type impurity element while using as masks the second shape gate electrodes; etching the second shape gate electrodes to form third shape gate electrodes; etching the third shape gate electrodes to form fourth shape gate electrodes; and doping the semiconductor layer in the p-channel TFT with a p-type impurity element while using the fourth shape gate electrodes as masks.
One of the features of the presnet invention is a method of manufacturing an electrice device, comprising: forming an amorphous semiconductor layer on an insulator; doping the amorphous semiconductor layer with a catalytic element for promoting crystallization; heating the amorphous semiconductor layer doped with the catalytic element to obtain a crystalline semiconductor layer; forming a gate insulating film on the crystalline semiconductor layer; forming a conductive film (A) and a conductive film (B) on the gate insulating film; etching the conductive film (A) and the conductive film (B) to form a gate electrode (A) and a gate electrode (C); doping the semiconductor layer with an n-type impurity element while using as masks the gate electrode (A) and the gate electrode (C); etching the gate electrodes (A) and (C) to form a gate electrode (B) and a gate electrode (D); doping the semiconductor layer with an n-type impurity element while using as masks the gate electrode (B) and the gate electrode (D); etching the gate electrode (D) of a p-channel TFT to form a gate electrode (E) while covering an n-channel TFT with a resist mask; and doping the semiconductor layer in the p-channel TFT with a p-type impurity element while using the gate electrode (E) as a mask.
One of the features of the presnet invention is a method of manufacturing an electrice device, comprising: forming an amorphous semiconductor layer on an insulator; doping the amorphous semiconductor layer with a catalytic element for promoting crystallization; heating the amorphous semiconductor layer doped with the catalytic element and then irradiating the amorphous semiconductor layer with a laser to obtain a crystalline semiconductor layer; forming a gate insulating film on the crystalline semiconductor layer; forming a conductive film (A) and a conductive film (B) on the gate insulating film; etching the conductive film (A) and the conductive film (B) to form a gate electrode (A) and a gate electrode (C); doping the semiconductor layer with an n-type impurity element while using as masks the gate electrode (A) and the gate electrode (C); etching the gate electrodes (A) and (C) to form a gate electrode (B) and a gate electrode (D); doping the semiconductor layer with an n-type impurity element while using as masks the gate electrode (B) and the gate electrode (D); etching the gate electrode (D) of a p-channel TFT to form a gate electrode (E) while covering an n-channel TFT with a resist mask; and doping the semiconductor layer in the p-channel TFT with a p-type impurity element while using the gate electrode (E) as a mask.
One of the features of the presnet invention is a method of manufacturing an electrice device, comprising: forming an amorphous semiconductor layer on an insulator; doping the amorphous semiconductor layer with a catalytic element for promoting crystallization; heating the amorphous semiconductor layer doped with the catalytic element to obtain a crystalline semiconductor layer; forming a gate insulating film on the crystalline semiconductor layer; forming a conductive film (A) and a conductive film (B) on the gate insulating film; etching the conductive film (A) and the conductive film (B) to form a gate electrode (A), a gate electrode (C), and a gate electrode (F); doping the semiconductor layer with an n-type impurity element while using as masks the gate electrodes (A), (C), and (F); etching the gate electrodes (A), (C), (F) to form a gate electrode (B), a gate electrode (D), and a gate electrode (G); doping the semiconductor layer with an n-type impurity element while using as masks the gate electrodes (B), (D), and (G); etching the gate electrode (D) of a p-channel TFT and the gate electrode (G) of a pixel TFT to form a gate electrode (Dxe2x80x2) and a gate electrode (H), respectively, while covering with a resist mask an n-channel TFT that is formed in a driving circuit; etching the gate electrode (Dxe2x80x2) to form a gate electrode (E); and doping the semiconductor layer in the p-channel TFT with a p-type impurity element while using the gate electrode (E) as a mask.
One of the features of the presnet invention is a method of manufacturing an electrice device, comprising: forming an amorphous semiconductor layer on an insulator; doping the amorphous semiconductor layer with a catalytic element for promoting crystallization; heating the amorphous semiconductor layer doped with the catalytic element to obtain a crystalline semiconductor layer; forming a gate insulating film on the crystalline semiconductor layer; forming a conductive film (A) and a conductive film (B) on the gate insulating film; etching the conductive film (A) and the conductive film (B) to form a gate electrode (A), a gate electrode (C), and a gate electrode (F); doping the semiconductor layer with an n-type impurity element while using as masks the gate electrodes (A), (C), (F); etching the gate electrodes (A), (C), (F) to form a gate electrode (B), a gate electrode (D), and a gate electrode (G); doping the semiconductor layer with an n-type impurity element while using as masks the gate electrodes (B), (D), (G); etching the gate electrode (D) of a p-channel TFT and the gate electrode (G) of a pixel TFT to form a gate electrode (Dxe2x80x2) and a gate electrode (H), respectively, while covering with a resist mask an n-channel TFT that is formed in a driving circuit; etching the gate electrode (Dxe2x80x2) to form a gate electrode (E); doping the semiconductor layer in the p-channel TFT with a p-type impurity element while using the gate electrode (E) as a mask; subjecting the insulator to heat treatment; covering the entire surface with an inorganic interlayer insulating film; forming an organic interlayer insulating film on the inorganic interlayer insulating film; forming a contact hole reaching the semiconductor layer through the inorganic interlayer insulating film and the organic interlayer insulating film; forming a pixel electrode on the organic interlayer insulating film; and forming a connection wiring line.
One of the features of the presnet invention is a method of manufacturing an electrice device, comprising: forming an amorphous semiconductor layer on an insulator; doping the amorphous semiconductor layer with a catalytic element for promoting crystallization; heating the amorphous semiconductor layer doped with the catalytic element to obtain a crystalline semiconductor layer; forming a gate insulating film on the crystalline semiconductor layer; forming a conductive film (A) and a conductive film (B) on the gate insulating film; etching the conductive film (A) and the conductive film (B) to form a gate electrode (A), a gate electrode (C), and a gate electrode (F); doping the semiconductor layer with an n-type impurity element while using as masks the gate electrodes (A), (C), (F); etching the gate electrodes (A), (C), (F) to form a gate electrode (B), a gate electrode (D), and a gate electrode (G); doping the semiconductor layer with an n-type impurity element while using as masks the gate electrodes; etching the gate electrode (D) of a p-channel TFT and the gate electrode (G) of a pixel TFT to form a gate electrode (Dxe2x80x2) and a gate electrode (H), respectively, while covering with a resist mask an n-channel TFT that is formed in a driving circuit; etching the gate electrode (Dxe2x80x2) to form a gate electrode (E); doping the semiconductor layer in the p-channel TFT with a p-type impurity element while using the gate electrode (E) as a mask; covering the entire surface with an inorganic interlayer insulating film; of gettering the catalytic element through heat treatment; forming an organic interlayer insulating film on the inorganic interlayer insulating film; forming a contact hole reaching the semiconductor layer through the inorganic interlayer insulating film and the organic interlayer insulating film; forming a pixel electrode on the organic interlayer insulating film; and forming a connection wiring line.
One of the features of the presnet invention is a method of manufacturing an electrice device, comprising: forming an amorphous semiconductor layer on an insulator; doping the amorphous semiconductor layer with a catalytic element for promoting crystallization; heating the amorphous semiconductor layer doped with the catalytic element and then irradiating the semiconductor layer with a laser to obtain a crystalline semiconductor layer; forming a gate insulating film on the crystalline semiconductor layer; forming a conductive film (A) and a conductive film (B) on the gate insulating film; etching the conductive film (A) and the conductive film (B) to form a gate electrode (A), a gate electrode (C), and a gate electrode (F); doping the semiconductor layer with an n-type impurity element while using as masks the gate electrodes (A), (C), (F); etching the gate electrodes (A), (C), (F) to form a gate electrode (B), a gate electrode (D), and a gate electrode (G); doping the semiconductor layer with an n-type impurity element while using as masks the gate electrodes (B), (D), (G); etching the gate electrode (D) of a p-channel TFT and the gate electrode (G) of a pixel TFT to form a gate electrode (Dxe2x80x2) and a gate electrode (H), respectively, while covering with a resist mask an n-channel TFT that is formed in a driving circuit; etching the gate electrode (Dxe2x80x2) to form a gate electrode (E); doping the semiconductor layer in the p-channel TFT with a p-type impurity element while using the gate electrode (E) as a mask; subjecting the insulator to heat treatment; covering the entire surface with an inorganic interlayer insulating film; forming an organic interlayer insulating film on the inorganic interlayer insulating film; forming a contact hole reaching the semiconductor layer through the inorganic interlayer insulating film and the organic interlayer insulating film; forming a pixel electrode on the organic interlayer insulating film; and forming a connection wiring line.
One of the features of the presnet invention is a method of manufacturing an electrice device, comprising: forming an amorphous semiconductor layer on an insulator; doping the amorphous semiconductor layer with a catalytic element for promoting crystallization; heating the amorphous semiconductor layer doped with the catalytic element and then irradiating the semiconductor layer with a laser to obtain a crystalline semiconductor layer; forming a gate insulating film on the crystalline semiconductor layer; forming a conductive film (A) and a conductive film (B) on the gate insulating film; etching the conductive film (A) and the conductive film (B) to form a gate electrode (A), a gate electrode (C), and a gate electrode (F); doping the semiconductor layer with an n-type impurity element while using as masks the gate electrodes (A), (C), (F); etching the gate electrodes (A), (C), (F) to form a gate electrode (B), a gate electrode (D), and a gate electrode (G); doping the semiconductor layer with an n-type impurity element while using as masks the gate electrodes (B), (D), (G); etching the gate electrode (D) of a p-channel TFT and the gate electrode (G) of a pixel TFT to form a gate electrode (Dxe2x80x2) and a gate electrode (H), respectively, while covering with a resist mask an n-channel TFT that is formed in a driving circuit; etching the gate electrode (Dxe2x80x2) to form a gate electrode (E); doping the semiconductor layer in the p-channel TFT with a p-type impurity element while using the gate electrode (E) as a mask; covering the entire surface with an inorganic interlayer insulating film; gettering the catalytic element through heat treatment; forming an organic interlayer insulating film on the inorganic interlayer insulating film; forming a contact hole reaching the semiconductor layer through the inorganic interlayer insulating film and the organic interlayer insulating film; forming a pixel electrode on the organic interlayer insulating film; and forming a connection wiring line.
One of the features of the presnet invention is a method of manufacturing an electrice device, comprising: forming an amorphous semiconductor layer on an insulator; doping the amorphous semiconductor layer with a catalytic element for promoting crystallization; heating the amorphous semiconductor layer doped with the catalytic element to obtain a crystalline semiconductor layer; forming a gate insulating film on the crystalline semiconductor layer; forming a conductive film (A) and a conductive film (B) on the gate insulating film; etching the conductive film (A) and the conductive film (B) to form a gate electrode (A), a gate electrode (C), and a gate electrode (F); doping the semiconductor layer with an n-type impurity element while using as masks the gate electrodes (A), (C), (F); etching the gate electrodes (A), (C), (F) to form a gate electrode (B), a gate electrode (D), and a gate electrode (G); doping the semiconductor layer with an n-type impurity element while using as masks the gate electrodes (B), (D), (G); etching the gate electrode (D) of a p-channel TFT and the gate electrode (G) of a pixel TFT to form a gate electrode (Dxe2x80x2) and a gate electrode (H), respectively, while covering with a resist mask an n-channel TFT that is formed in a driving circuit; etching the gate electrode (Dxe2x80x2) to form a gate electrode (E); removing the gate insulating film while using the gate electrode (B), the gate electrode (E), and the gate electrode (H) as masks; and doping the semiconductor layer in the p-channel TFT with a p-type impurity element while covering the n-channel TFT and the pixel TFT with a resist mask and using the gate electrode (E) as a mask.
One of the features of the presnet invention is a method of manufacturing an electrice device, comprising: forming an amorphous semiconductor layer on an insulator; doping the amorphous semiconductor layer with a catalytic element for promoting crystallization; heating the amorphous semiconductor layer doped with the catalytic element and then irradiating the semiconductor layer with a laser to obtain a crystalline semiconductor layer; forming a gate insulating film on the crystalline semiconductor layer; forming a conductive film (A) and a conductive film (B) on the gate insulating film; etching the conductive film (A) and the conductive film (B) to form a gate electrode (A), a gate electrode (C), and a gate electrode (F); doping the semiconductor layer with an n-type impurity element while using as masks the gate electrodes (A), (C), (F); etching the gate electrodes (A), (C), (F) to form a gate electrode (B), a gate electrode (D), and a gate electrode (G); doping the semiconductor layer with an n-type impurity element while using as masks the gate electrodes (B), (D), (G); etching the gate electrode (D) of a p-channel TFT and the gate electrode (G) of a pixel TFT to form a gate electrode (Dxe2x80x2) and a gate electrode (H), respectively, while covering with a resist mask an n-channel TFT that is formed in a driving circuit; etching the gate electrode (Dxe2x80x2) to form a gate electrode (E); removing the gate insulating film while using the gate electrode (B), the gate electrode (E), and the gate electrode (H) as masks; and doping the semiconductor layer in the p-channel TFT with a p-type impurity element while covering the n-channel TFT and the pixel TFT with a resist mask and using the gate electrode (E) as a mask.
In the above method, wherein the gate electrode (B), the gate electrode (E), and the gate electrode (H) are formed from the conductive film (A) and the conductive film (B), and the conductive film (A) is wider than the conductive film (B).
In the above method, wherein the laser used to irradiate the semiconductor layer that is doped with the catalytic element is a pulse oscillation type KrF excimer laser, XeCl excimer laser, YAG laser, or YVO4 laser.
A method of manufacturing an electro-optical device (semiconductor device) according to the present invention will be described. A conductive film (A) and a conductive film (B) are formed on a gate insulating film and patterned to form gate electrodes. In forming the gate electrodes, a gate electrode of an n-channel TFT is obtained by patterning the conductive films into a given shape. For a gate electrode (C) of a p-channel TFT, on the other hand, the conductive film (A) and the conductive film (B) are patterned in this etching step such that the gate electrode (C) is wider in the channel length direction than a gate electrode (B) of the n-channel TFT. This is for using later the gate electrode (C) as a mask in an n-type impurity element doping step so as to prevent a region doped with an n-type impurity element from getting too large in a semiconductor layer of the p-channel TFT. Using the gate electrode (C) as a mask, a region in the semiconductor layer that does not overlap the gate electrode (C) is doped with phosphorus (P). The region doped with phosphorus (P) functions as a gettering sink.
A gate electrode (D) of the p-channel TFT is next patterned into a given shape to form a gate electrode (E) having the given shape. Thereafter, the semiconductor layer of the p-channel TFT is doped with boron (B) to give the layer the p-type conductivity. Through the above steps, a channel forming region, a region doped with phosphorus (P) and boron (B), and a region doped with boron (B) alone are formed in the semiconductor layer of the p-channel TFT.
According to the present invention, the distance the catalytic element travels in the semiconductor layer of the p-channel TFT during gettering can be shortened. As a result, less catalytic elements segregate in crystal grain boundaries and therefore leak path of a small amount of current and an abrupt increase in OFF current due to the segregation take place less frequently. The characteristic and the reliability of the TFT are thus improved.

Method of manufacturing a TFT using a catalytic element to promote crystallization of a semiconductor film and gettering the catalytic element

Semiconductor Energy Laboratory Co., Ltd.


Systems and methods for providing convolutional neural network based image synthesis using localized loss functions is disclosed. A first image including desired content and a second image including a desired style are received. The images are analyzed to determine a local loss function. The first and second images are merged using the local loss function to generate an image that includes the desired content presented in the desired style. Similar processes can also be utilized to generate image hybrids and to perform on-model texture synthesis. In a number of embodiments, Condensed Feature Extraction Networks are also generated using a convolutional neural network previously trained to perform image classification, where the Condensed Feature Extraction Networks approximates intermediate neural activations of the convolutional neural network utilized during training.

With the growth and development of creative projects in a variety of digital spaces (including, but not limited to, virtual reality, digital art, as well as various industrial applications), the ability to create and design new works based on the combination of various existing sources has become an area of interest. However, the actual synthesis of such sources is a hard problem that raises a variety of difficulties.

Systems and methods for providing convolutional neural network based image synthesis using stable and controllable parametric models, a multiscale synthesis framework and novel network architectures


A photoelectric conversion device includes a photoelectric conversion unit including a first and second electrodes, a photoelectric conversion layer between the first and second electrodes, and an insulating layer between the photoelectric conversion layer and the second electrodes, an amplifier unit connected to the second electrode and outputs a signal generated in the photoelectric conversion unit, and a reset unit for resetting a voltage of the second electrode. An accumulating operation for accumulating signal charges in the photoelectric conversion unit and a charge removing operation for removing the signal charges from the photoelectric conversion unit are alternately executed in accordance with a voltage applied between the first and second electrodes, and the charge removing operation is executed multiple times between a first accumulating operation and a second accumulating operation which is executed after the first accumulating operation.

Field of the Invention
The present invention relates to a photoelectric conversion device and an imaging system.
Description of the Related Art
As a photoelectric conversion device which is used for an image sensor of a camera or the like, a stacked-type photoelectric conversion device has been proposed. In a photoelectric conversion device disclosed in FIG. 1 of International Publication No. WO2012/004923, a photoelectric conversion film is stacked over a semiconductor substrate. A transparent electrode is arranged on the photoelectric conversion film and a pixel electrode is arranged under the photoelectric conversion film. An insulating film is arranged between the photoelectric conversion film and the pixel electrode. The International Publication No. WO2012/004923 discloses such a point that since correlated double sampling can be performed by such a construction, noise can be reduced.
In the photoelectric conversion device disclosed in the International Publication No. WO2012/004923, after a voltage VPk which is applied to the transparent electrode is swung, a signal readout is performed. Although a time which is required for the readout is not disclosed, dark electric charges and photo-induced charges are accumulated in the photoelectric conversion film for a period of time until the readout is finished, and residual charges are generated after the readout and become an error of a light signal component.

Photoelectric conversion device and imaging system


An electronic component package and a manufacturing method thereof are disclosed. The electronic component package manufacturing method, which includes mounting an electronic component in one surface of a first insulation layer; bonding a heat sink to the one surface of the first insulation layer, corresponding to the electronic component, to cover the electronic component, the heat sink being formed with a cavity; charging the cavity with an adhesive; and forming a circuit pattern in the other surface of the first insulation layer, can prevent a void from being generated in the adhesive, make the handling stable and make the size small by allowing the heat sink formed with the cavity to cover the electronic component before the pattern build-up and supplying the adhesive through one side of the cavity while providing negative pressure through the other side.

1. Field of the Invention
The present invention relates to an electronic component package and a manufacturing method thereof.
2. Background Art
Today's trend of the current electronic part industry shows that the number of input/output of chips has risen sharply, and the package is multifunctional and multiplex. Accordingly, a chip scale package that packages a chip scale as it is without using a solder and a solder bump of a flip chip ball grid array (BGA) has been developed.
FIG. 1A through 1K illustrate an electronic component package manufacturing method in accordance with a conventional art, and FIG. 2 is a sectional view showing an electronic component package in accordance with a convention art. As shown in FIG. 1 and FIG. 2, according to the electronic component package manufacturing method in accordance with the conventional art, a void may be generated in the process of molding a chip 1. Since the process of assembling a heat sink and lay-up process, for example, are performed after the chip 1 is molded in a flexible printed circuit board 2 by using a dam member 3 and an adhesive 4, the handling may be unstably performed.
Also, as shown in FIG. 2, the durability may be lowered due to allowing the heat sink 8 to be coupled to the dam member 3 by use of an adhesive 7, and the heat-emitting efficiency may be lowered due to the structure in which only one side surface of the electronic component 1 is arranged facing the heat sink 8.

Electronic component package and manufacturing method thereof


An anastomosis training device and related methods of use that provides medical professionals with real-time feedback of pulling force. The anastomosis training device can include a housing portion, a spring member, a proximal catheter portion and a distal catheter portion. The housing portion can include an external tubing member that slidingly retains an internal tubing element and the spring member. A proximal wire assembly attaches the spring member to a manipulation assembly and a distal wire assembly attaches the spring member to a retention member that allows the anastomosis training tool to be anchored to a suitable surface. As a user applies a pulling force to the manipulation assembly, the internal tubing member is slidably withdrawn from the external tubing member to expose a visible force scale that indicates the level of pulling force being applied by the user.

Biological lumens can be severed through a variety of causes including, for example, accidental injury or intentional surgical procedures. For example, individuals can choose to be permanently sterilized through the surgical severing of the fallopian tubes in females or the severing of the vas deferens in males. However, in some instances, individuals can subsequently desire to reverse the sterilization procedure by restoring the severed biological lumen. In other cases, biological lumens severed by injury or disease can also require restoration. The severed biological lumen can be restored by rejoining the severed biological lumen through an anastomosis procedure.
Anastomosis procedures typically involve the realignment and reconnection of the opposed stumps of the severed biological lumen and retaining the stumps together until the biological lumen is restored. However, the traditional suturing based procedure is hampered by the difficulty of effectively suturing the relatively small biological lumen or the close proximity of the surgical site to sensitive tissues, which increases the risk of the procedure being performed incorrectly and complications arising from the anastomosis procedure. Complications specific to the surgical site could include leakage of the biological lumen, difficulty in healing or outright failure of the wound to heal. General complications such as incontinence or impotence can also result if the procedure is not properly performed.
Various anastomosis devices have been developed that use alternative means of rejoining the severed biological lumens and retaining the stumps until the biological lumen is restored instead of the traditional sutures. Commercially, a representative anastomosis device includes those available from American Medical Systems of Minnetonka, Minn. and which are further described in U.S. Patent Publication Nos. 2004/0087995, 2005/0070938, 2005/0131431, 2006/0200178, 2006/0264985, 2006/0276811 and 2007/0219584, all of which are hereby incorporated by reference in their entireties. An anastomosis device can generally comprise an elongated body have a pair of deployable approximation structures disposed at a distal working end of a device body. Typically, the anastomosis device comprises a catheter style body which is inserted through the severed lumen until at least the distal working end of the anastomosis device protrudes from a proximalmost stump. A manipulation assembly at a proximal end of the catheter allows a medical professional to control the positioning of the anastomosis device and the deployment/retraction of the approximation structures at the distal working end. The distal working end of the anastomosis device is then advanced into a lumen opening on a distal stump such that the distal stump can be grasped and retained by deploying a distalmost set of approximation structures. A pulling force is then applied to the manipulation assembly of the anastomosis device to draw the distal and proximal stumps into operational contact to restore the biological lumen. In a typical anastomosis procedure, the pulling force applied by the medial professional is ideally be between 1 and 2 pounds of force to insure the distal and proximal stumps are properly joined without damaging the tissue of the biological lumen.
The pulling force is typically applied by medical personnel to the manipulation assembly which translates the pulling force to anastomosis device via the catheter body as well as wires disposed within the catheter body that operably connect the manipulation assembly with the distal treatment end. As the ideal range of the pulling force is relatively small, it can be difficult for inexperienced medical personal to successfully apply the pulling forces. As such, it would be advantageous to allow medical professionals to simulate the application of pulling force prior to conducting an actual anastomosis procedure.

Anastomosis deployment force training tool


A reclosable battery package includes a first panel having a first removable portion and a second panel optionally having a second removable portion. A pouch is disposed between the first panel and the second panel. The first panel and the second panel are joined along perimeter edges and a pouch perimeter flange is disposed between the first panel and the second panel. The pouch is slidably movable between the first panel and the second panel when the first removable portion is removed from the first panel to expose contents stored within the pouch.

Electrochemical cells, or batteries, are commonly used as electrical energy sources. Small batteries are especially useful in powering consumer products. Small batteries come in a variety of sizes. Common small battery sizes are AAA, AA, C, D, and 9V. However, other types of small batteries are also available for other types of products, such as watches, cameras, etc. Because typical consumer products often require significant amounts of energy to function, multiple batteries are often required to operate a single product. Often consumers will use more than one consumer product, which multiplies the battery requirement. As a result, consumers may purchase packages of batteries (sometimes including as many as 40 or more batteries in a single package) so that they do not have to return to the store often.
Battery packages may include a plastic front portion that is adhered to a paper or cardboard back portion. The plastic front portion is usually clear so that the consumer can see the type of battery in the package, although the plastic front portion does not have to be clear. A utensil, such as scissors or a knife, may be needed to open a battery package. This presents problems to the consumer when such a utensil is not readily available. Additionally, once the package is opened (either by cutting the adhered portion of the plastic front portion, or by punching a hole in the paper or cardboard back portion), the unneeded batteries may fall out of the opening, which often causes consumers to store the unneeded batteries in a bag of some sort until they are needed later. This leads to unnecessary clutter and it also subjects the unneeded batteries to damage as well inadvertent discharge, or shorting, should the battery(ies) come into contact with a substance that completes an electrical circuit.
While some battery packages have been developed that include perforations in the paper or cardboard back portion, to make the package easier to open, such packages may be susceptible to unintentional opening during transportation, particularly if the packages are handled roughly. Moreover, these types of packages also may allow all batteries to come out of the package once the package is opened. So the consumer still needs to store the unneeded batteries as discussed above.


A spectacle holder including: a loop member; and a sliding member slidingly disposed on the loop member; wherein the sliding member slides on the loop member to capture a portion of a spectacle in a portion of the loop member. The sliding member can be decorative, such as a charm, broach, or pendant. The sliding member can also have one or more holes therethrough for acceptance of first and second strands of the loop member, the one or more holes having an exit located above a lower portion of the sliding member such that the portion of the loop member is hidden from view when worn by a user and no spectacle is captured.

1. Field of the Invention
The field of art to which this invention relates is spectacle holders, and more particularly to a loop/lariat spectacle holder.
2. Description of the Related Art
Eyeglass holders worn by a user for suspending eyeglasses therefrom are well known in the art. Such eyeglass holders are disclosed in U.S. Pat. Nos. 5,033,612; 5,680,191; and 6,075,925. Such eyeglass holders are useful for users, who don't always need to wear their eyeglasses, who do not want to always wear their eyeglasses, or who wish to carry another pair of eyeglasses, such as sunglasses. For such people, the eyeglass holders provide a convenient place to carry their eyeglasses while they are not being worn, and in some instances, such as in the eyeglass holders disclosed in U.S. Pat. Nos. 5,860,191, Des 465,327, and Des 487,344, they do so in an attractive and decorative manner. The contents of U.S. Pat. Nos. 5,860,191, Des 465,327, and Des 487,344, are incorporated herein by their reference in their entirety.
Although such decorative eyeglass holders have utility and advantages over the spectacle holders known prior thereto, they generally do not positively "trap" the spectacles or double as a necklace when not used to hold spectacles.