Analogs of the serine protease inhibitors in which the amino acid sequence is varied slightly are disclosed, which analogs variously show improved properties including improved resistance to oxidative inactivation, improved ability to inhibit pancreatic elastase, improved ability to inhibit cathepsin G, and improved ability to inhibit trypsin.

Endogenous proteolytic enzymes serve to degrade invading organisms, antigen-antibody complexes and certain tissue proteins which are no longer necessary or useful to the organism. In a normally functioning organism, proteolytic enzymes are produced in a limited quantity and are regulated in part through the synthesis of protease inhibitors.
A large number of naturally occurring protease inhibitors serve to control the endogenous proteases by limiting their reactions locally and temporally. In addition, the protease inhibitors may inhibit proteases introduced into the body by infective agents. Tissues that are particularly prone to proteolytic attack and infection, e.g. those of the respiratory tract, are rich in protease inhibitors.
Protease inhibitors comprise approximately 10% of the human plasma proteins. At least eight inhibitors have been isolated from this source and characterized in the literature. These include .alpha..sub.2 -macroglobulin (.alpha..sub.2 M), .alpha..sub.1 -protease inhibitor (.alpha..sub.1 PI), .alpha..sub.1 -antichymotrypsin (.alpha..sub.1 Achy), .alpha..sub.1 -anticollagenase (.alpha..sub.1 AC), and inter-.alpha.-trypsin inhibitor (I.alpha.I).
A disturbance of the protease/protease inhibitor balance can lead to protease-mediated tissue destruction, including emphysema, arthritis, glomerulonephritis, periodontitis, muscular dystrophy, tumor invasion and various other pathological conditions. In certain situations, e.g. severe pathological processes such as sepsis or acute leukemia, the amount of free proteolytic enzymes present increases due to the release of enzyme from the secretory cells. In addition, or separately in other situations, a diminished regulating inhibitor capacity of the organism may also cause alterations in the protease/protease inhibitor balance. An example of such a diminished regulating inhibitor capacity is an .alpha..sub.1 -protease inhibitor deficiency, which is highly correlated with the development of pulmonary emphysema.
In organisms where such aberrant conditions are present, serious damage to the organism can occur unless measures can be taken to control the proteolytic enzymes. Therefore, protease inhibitors have been sought which are capable of being administered to an organism to control the proteolytic enzymes.
One protease that is of particular pharmacological interest is leukocyte elastase. Leukocyte elastase, when released extracellularly, degrades connective tissue and other valuable proteins. While it is necessary for a normally functioning organism to degrade a certain amount of connective tissue and other proteins, the presence of an excessive amount of leukocyte elastase has been associated with various pathological states, such as emphysema and rheumatoid arthritis. To counteract the effects of leukocyte elastase when it is present in amounts greater than normal, a protease inhibitor has been sought which is specific for leukocyte elastase. Such a protease inhibitor would be especially useful if it were capable of being isolated or prepared in a purified form and in sufficient quantities to be pharmaceutically useful
In the past, at least two leukocyte elastase inhibitors have been identified in the literature. One protein, described in Schiessler et al., "Acid-Stable Inhibitors of Granulocyte Neutral Proteases in Human Mucous Secretions: Biochemistry and Possible Biological Function", in Neutral Proteases of Human Polymorphoneuclear Leucocytes, Havemann et al. (eds), Urban and Schwarzenberg, Inc. (1978), was isolated from human seminal plasma and sputum and was characterized as being approximately 11 Kda in size with tyrosine as the N-terminal amino acid. The literature reports of this protein have only furnished a partial amino acid sequence, but even this partial sequence indicates that this protein varies substantially from the proteins of the present invention. The reports of the sequence of this protein, in combination with the complete amino acid sequence data for proteins of the present invention, indicate to the present inventors that the product sequenced by Schiessler et al. may have been a degraded protein which was not a single-polypeptide chain.
A second protein, isolated in one instance from human plasma, has been named .alpha..sub.1 -protease inhibitor. Work on this protein has been summarized in a review by Travis and Salvesen, Annual Review of Biochemistry 52: 655-709 (1983). The reports of the amino acid sequence of this protein indicate that it too differs substantially from the proteins of the present invention.
Because of the substantial differences in structure between single-polypeptide-chain proteins of the present invention and any single-polypeptide-chain serine protease inhibitors of the prior art, the single-polypeptide-chain serine protease inhibitors of the prior art are not "substantially homologous" to the proteins of the present invention.
Trypsin is another protease of particular interest from a pharmacological standpoint. Trypsin is known to initiate degradation of certain soft organ tissue, such as pancreatic tissue, during a variety of acute conditions, such as pancreatitis. A variety of efforts have been directed toward the treatment of these conditions, without marked success, through the use of proteins which it was hoped would inhibit the action of trypsin. Illustrative of such efforts are attempts to use exogenous bovine trypsin inhibitors in treatment of human pancreatitis. While such techniques have been attempted in Europe, they have not been approved as effective by the U.S. Food and Drug Administration.
Thus, there is a need for a protease inhibitor effective in neutralizing excess trypsin in a variety of acute and chronic conditions. As was the case with the leukocyte elastase inhibitor discussed above, a trypsin inhibitor would be particularly useful if it could be isolated and prepared in a purified form and in sufficient quantities to be pharmaceutically useful.
Cathepsin G is another protease present in large quantities in leukocytes. Cathepsin G is known to be capable of degrading in vitro a variety of valuable proteins, including those of the complement pathway Pancreatic elastase is another protease which may have a role in pancreatitis. Thus, inhibitors for these proteases are also of potential pharmaceutical value.
Leukocyte elastase, trypsin, cathepsin G and pancreatic elastase are examples of a class of proteases known as serine proteases, which have elements of common structure and mechanism Their activity against different substrates and their sensitivity to different inhibitors are believed to result from changes in only a few amino acid residues By analogy, it is possible to conceive of a class of serine protease inhibitors, also having common elements of structure and mechanism, in which changes in a relatively few amino acids will result in inhibition of different proteases, and that at least one member of this class will inhibit every serine protease of the former class. The class of serine protease inhibitors would then be of substantial values
Surprisingly, the present inventors have found a 12 Kda protease inhibitor, isolated in purified form from parotid secretions, in which the amino acid sequence varies greatly from the reported sequences of single-polypeptide-chain serine protease inhibitors. The protease inhibitor of the present invention is believed to have at least two active sites. One site exhibits leukocyte elastase inhibiting properties while a second site exhibits activity against trypsin. The present inventors have accurately sequenced the entire length of the novel protease inhibitor. This sequence is set forth more fully hereinafter


This invention relates to methods and compositions for materials having a non-leaching coating that has antimicrobial properties. The coating is applied to substrates such as gauze-type wound dressings. Covalent, non-leaching, non-hydrolyzable bonds are formed between the substrate and the polymer molecules that form the coating. A high concentration of anti-microbial groups on multi-length polymer chains and relatively long average chain lengths, contribute to an absorbent or superabsorbent surface with a high level antimicrobial effect.

The importance of sterile techniques and especially sterile bandage material to modern medicine can hardly be overestimated. Almost every student of biology has heard the tales of how medical practitioners of not too long ago thought that pus and other signs of what is now known to be infection were essential to wound healing. These practitioners would reopen a wound that was not showing the expected pus and inflammation. This was changed by Lister's discoveries regarding disinfection and the subsequent adoption of sterile bandage material for wound dressings. A continuing problem has been the propensity for microorganisms to grow in once sterile bandage material.
A major function of surgical bandages and packing materials is the absorption of various excreted fluids. These fluids are frequently rich in nutrients and are capable of supporting abundant bacterial growth. Since the surgical opening or skin surface is rarely absolutely free of bacteria, the bandage material soon supports a burgeoning bacterial population. These bacteria can easily cause serious infection and may also release a variety of harmful toxins. The obvious solution to such a problem is to change the bandage material often so that bacterial buildup does not occur. An additional approach is to treat the bandage material with some type of disinfectant to limit bacterial growth. Unfortunately, it has proven difficult to produce an effective disinfectant that does not readily wash out of the material. Such wash out, or leaching, reduces effectiveness and may cause irritation or damage to body tissues.
This problem is not limited to bandages, dressings or packings for wounds or surgical incisions. There are a number of instances where absorptive packings are placed in natural body orifices with significant possibility for dangerous bacterial growth. Various nasal packings can become bacterially laden following insertion into nasal passageways. Numerous deaths have resulted from "toxic shock syndrome" resulting from multiplication of Staphylococcus aureus bacteria in feminine care products, particularly tampons. There have been a large number of related problems. For example, U.S. Pat. No. 5,641,503, to Brown-Skrobot, seeks to produce a germicidal tampon and contains a useful list of references to the toxic shock problem. A particular difficulty has been that many potent germicidal agents, e.g. iodine, are partially or totally ineffective in the presence of protein rich solutions such as blood or menses.
In addition, due to the globalization of commerce, the emergence of new diseases, the risks of biological warfare, the contamination of food products with highly pathogenic strains of bacteria, and other forces on society, the uses for a technology that imparts a non-leaching antimicrobialcoating to a variety of surfaces is duly recognized. Specific areas of use in addition to bandage material are described below in the Summary of the Invention section.
In connection with the care and treatment of wounds, the term "wound" is meant to include burns, pressure sores, punctures, ulcers and the like. For a long time, one critical aspect of wound care has been the consideration of the requirements of the epithelium, i.e., that area of new cell growth directly peripheral to the wound which is formed during the healing process, so that healing is facilitated.
Since it has been recognized that healing of the wound occurs in one sense as the epithelium migrates by growth from the periphery inward, care has been taken not to damage unnecessarily or to irritate this new area of growth or existing, compromised periwound tissue. With many dressings, problems can occur during dressing changes. This is particularly true where the dressing adheres to the epithelium or where granulation tissue and new cell growth become intertwined within the matrix of a dressing. In these instances, there is a risk that removal of the dressing will damage the sensitive tissue and new growth on the periphery of the wound thereby causing a regression in the progress of wound healing.
Another consideration in wound care is the frequency of dressing changes. The time frame for the changing of dressings depends on many concerns and therefore opinions as to how often dressings should be changed vary drastically.
Still, another important consideration in wound care is the needs of the surrounding unwounded skin. The unwounded skin beyond the epithelium is usually in contact with some portion of the wound dressing system which maintains the dressing positioned on the wound. For example, the surrounding skin may be covered for extended periods with a wrap and/or adhesive to hold the dressing in place. Many such dressings can irritate this surrounding skin and compound problems to the patient. This is especially true in the area of leg ulcers wherein the surrounding skin can easily become sensitized by strong medicaments and is often plagued with flaking, scaling and eczema.
One type of treatment presently used, in particular for leg ulcers, comprises the application of gauze to the ulcer and the utilization of a compression wrap to secure the gauze to the ulcer. Since the gauze quickly becomes saturated, frequent changes are necessary and damage to the epithelium and surrounding skin may occur. Moreover, if the gauze is left on for too long a period, the exudate can begin to overly hydrate and macerate the patient's surrounding skin.
A second type of treatment, also used in particular for leg ulcers, is the Unna's Boot (commercially available from Biersdorf, Inc.) which comprises a zinc paste-containing bandage wrapped around a patient's leg from above the toes to below the knee. Other Unna's Boot/zinc impregnated treatments are available from Miles and Graham Field. These dressings are typically left in place for a week at a time and absorbent pads must be applied to the outside of the dressings in the area of the ulcer to absorb excess exudate. Seepage of exudate throughout the wrap is common, and damage to the skin and epithelium is inevitable.
Another type of wound dressing is disclosed in U.S. Pat. No. 5,106,362 to Gilman. This dressing is provided with a base sheet for contacting the skin of a patient. The base sheet has an opening for placement over the wound. The dressing has a vent for providing controlled leakage of fluid along a path from the wound through the opening of the base sheet. The vent is designed to provide control over wound leakage along a "tortuous path" from the wound through the opening of the base sheet.
A modification of the dressing of U.S. Pat. No. 5,106,362 is disclosed in U.S. Pat. No. 5,056,510, also to Gilman. The '510 patent discloses a vented dressing where the fabric reservoir for wound exudate is contained within a chamber. The walls of the chamber are intended to provide a barrier to bacterial and other contaminants. The walls of the chamber are also intended to be air permeable so as to permit egress of air from the voids of the fabric reservoir. These Gilman dressings do not especially address the problems of the epithelium and the surrounding skin.
It is apparent that, considering the various types of wounds, the numerous dressings that are available, and the various stages of healing, there is still a tremendous need for a dressing that functions better than the current dressings, especially with respect to preventing damage to surrounding skin, tissue and new cell growth. In particular, a wound dressing system which protects the epithelium and surrounding non-wounded skin, which wicks away moisture from the wound area, and which does not purposely adhere to the wound or the surrounding area would be a useful addition to the wound care art. A dressing for patients with fragile skin surrounding a wound would be especially beneficial.
Certain wound dressing materials have been used to absorb exudate and promote healing. For example, Mason, et al., U.S. Pat. No. 4,393,048 teaches a hydrogel composition which, when applied as a powder, absorbs wound exudate. The hydrogel formation may not be complete and lumps of partially hydrated powders form which, when removed, may reopen the wound.
It is known that wounds heal more rapidly and completely if kept in a slightly moist or hydrated state. Polyethylene glycol containing hydrogel wound coverings are disclosed in U.S. Pat. No. 4,226,232, to Spence. These hydrogels cannot be sterilized by irradiation due to the formation of free radicals.
Rawlings et al., U.S. Pat. No. 4,657,006, illustrate wound dressings comprised of a hydrophilic polymer having moisture and vapor permeability properties. However, the exudate absorbed by the hydrophilic polymer tends to harden or solidify the polymer.
An ideal wound dressing should not only absorb exudate but also possess antimicrobial or antibacterial properties. As used in this disclosure, "antibacterial" is defined as having an adverse effect on bacteria, particularly disease-causing bacteria. Furthermore, "antimicrobial" is defined as having an adverse effect on a range of microorganisms, including bacteria and at least some fungi and viruses. An antimicrobial wound dressing is generally preferred over an antibacterial wound dressing.
One example of an antimicrobial wound dressing is Matson, U.S. Pat. No. 4,728,323, which discloses a wound dressing comprising a substrate coated with a coating of a silver salt that allegedly also keeps the wound moist. Since the active agent (silver ion) is not covalently bound to the dressing material, there is a potential for leaching into the body and/or depletion of the active agent.
In the past, wounds have been treated with antimicrobial active agents applied to the wound and covered with a covering that inhibits the healing process. For example, it was conventional practice early in the 20th Century to apply an antiseptic mercury agent such at thimerosal (Merthiolate) or merbromin (Mercurochrome) and the like to a wound and then cover or wrap the wound with a bandage such as gauze or an adhesive strip having a central absorbent gauze portion. A disadvantage of this approach is that the wound often weeps or exudes fluids such as blood, pustulation and the like. While the gauze may absorb some of these fluids, the gauze often adheres to the wound such that removal of the dressing reopens the wound. Advances in the art have been made in both bandages and antimicrobial agents. Certain bandages now contain a nonadhering polymeric coating over or, in place of, the gauze that inhibits the adhering of the absorbent material to the wound but also inhibits the absorption of the exudate that is necessary to properly heal the wound.
Korol, U.S. Pat. No. 4,563,184, discloses wound dressings comprising a polymer, such as poly(2-hydroxyethylmethacrylate), a solvent, such as polyethylene glycol, and a plasticizer such as DMSO. An antimicrobial agent, such as silver sulfadiazine, may be incorporated into the polymeric material.
Widra, U.S. Pat. No. 4,570,629, is drawn to absorbent hydrogel membrane wound dressings made up of hydrophilic biopolymeric copolyelectrolytes comprising a water-soluble linear anionic protein polyelectrolyte component derived from keratin and a water-soluble linear cationic biopolymer polyelectrolyte component derived from either collagen or a glycosaminoglycan. The membranes may also contain antibiotics.
Klemm et al., U.S. Pat. No. 4,191,743, teach the administration of antibiotics to wounds using a wound dressing comprising at least two layers of synthetic resin arranged one above the other having an intermediate layer composed of a synthetic resin granulate having an antibiotic incorporated therein.
Hansen et al., U.S. Pat. No. 5,498,478 is directed to the use of a polyethylene glycol or similar polymer as a binder material for fibers of any variety. The binder and fibers may be pretreated by slurrying the fibers in baths containing antimicrobial agents as part of the solution, thereby causing the fibers and the subsequently formed matrix of polymer and fibers to have an antimicrobial ability.
Mixon et al., U.S. Pat. No. 5,069,907 is directed to the formation and use of a polymeric sheet which may include an antimicrobial agent. This patent teaches of the inclusion of antimicrobial agents into either a pressure-sensitive layer, such as an adhesive, or in a drape used to cover a wound or other sensitive area.
Dietz et al., U.S. Pat. Nos. 5,674,561 and 5,670,557 are directed to polymerized microemulsion pressure sensitive adhesive compositions that may optionally contain antimicrobial and/or other biologically active agents. The potential antimicrobial activity of quaternary amine and quaternary ammonium salts is taught. It is further taught that an antimicrobial agent can be added so as to be contained in a specific layer of a pressure sensitive adhesive device for use as a medical skin covering and/or as a wound dressing.
Young et al., U.S. Pat. No. 5,432,000, teach the use of a polymeric network for adhering particulate materials to a fiber or fibrous product. Specifically, this patent teaches of the use of polymers, such as polyethylene glycol or polyethylene to cause the binding of particulate materials to a fiber, such as cloth. One such particulate member which could be adhered to cloth is an antimicrobial agent, such as epoxide phenol or another antimicrobial substance.
U.S. Pat. No. 5,811,471, to Shanbrom, teaches immobilization of germicidal dyes such as methylene blue onto polyvinyl alcohol gels. The dyes are not covalently bound; however, and thus have the potential to be desorbed. This potential shortcoming is discussed in '471: "Even though dyed PVA appears non-irritating, there might be some concern that the disinfectant dye molecules could migrate to human tissue in contact with the material". Another potential drawback discussed therein is that the dyes are strongly colored, and hence may not be visually appealing to the consumer: "In the case of some products like tampons a "clean" white product might be psychologically more acceptable".
In U.S. Pat. No. 4,643,181, Brown discusses mixing an antimicrobial biguanide compound with an adhesive. The adhesive polymer is incorporated into the system to bind the biguanides (which are desorbed from the non-woven material when it is wetted by urine. It is clear from the data that the biguanide antimicrobial leaches from the material, and thus it is a drug-releasing system.
A number of antimicrobial systems based on leaching of low concentrations of silver ion from surfaces have also been reported. For instance, U.S. Pat. Nos. 6,126,931 and 6,030,632 describe a biguanide polymer (PHMB) bonded a substrate. Silver salts are then bonded to the immobilized PHMB. The surface-bound PHMB alone does not inhibit bacterial growth, but it does bind the bacteria, thus allowing the low-solubility silver salts to function.
A similar invention is reported in U.S. Pat. No. 5,662,913, to Capeli, wherein wound dressings which contain silver salts are discussed. The silver is stabilized by polyether polymers.
Another similar method is described in U.S. Pat. No. 5,856,248, to Weinberg, except that copper salts are used instead of silver.
The leaching of silver from elemental silver coatings on medical textiles is described by Tweden et al. ("Silver Modification of Polyethylene Terephthalate Textiles for Antimicrobial Protection"; ASAIO Journal, 43, pM475-M481 (1997). In that study the leaching of silver was equivalent to a serum silver concentration of 55 ppb in an adult human of normal blood volume.
In U.S. Pat. No. 5,985,301, Nakamura describe cellulose fiber that contains silver as an antibacterial agent. In short, cellulose is dissolved in a particular type of solvent, and then silver compounds are added. Fibers are then spun from these solutions. It is reported that these fibers have bactericidal properties. This method must be considered a drug-releasing technology. This fact is emphasized by the following quote from the Nakamura patent: " . . . enhancing antibacterial effects presumably by promoting the discharge of silver ions from the silver-based antibacterial agent."
It is known that certain quaternary ammonium salts possess antimicrobial properties. Examples include benzethonium chloride and benzalkonium chloride (BACTINE). It is also known that certain low molecular weight quaternary ammonium groups can be incorporated into polymeric substrates (without chemical bonding) in order to provide certain degrees of antimicrobial activity.
Ionene polymers or polymeric quaternary ammonium compounds (polyquats), i.e., cationic polymers containing quaternary nitrogens in the polymer backbone, belong to a well-known class of biologically-active compounds. See, e.g., A. Rembaum, Biological Activity of Ionene Polymers, Applied Polymer Symposium No. 22, 299-317 (1973). Ionene polymers have a variety of uses in aqueous systems such as microbicides, bactericides, algicides, sanitizers, and disinfectants. U.S. Pat. Nos. 3,778,476, 3,874,870, 3,898,336, 3,931,319, 4,013,507, 4,027,020, 4,089,977, 4,111,679, 4,506,081, 4,581,058, 4,778,813, 4,970,211, 5,051,124, and 5,093,078 give various examples of these polymers, their preparation, and their uses. U.S. Pat. Nos. 3,778,476, 3,898,536, and 4,960,590, in particular, describe insoluble tri-halide containing ionene polymers. U.S. Pat. No. 4,013,507 describes ionene polymers which selectively inhibit the growth of malignant cells in vitro.
Hou et al., U.S. Pat. No. 4,791,063, teach polyionene-transformed modified polymer-polysaccharide separation matrices for use in removing contaminants of microorganism origin from biological liquids. This patent teaches that absorption of bacterial cells by ion-exchange resins is attributable to electrostatic attraction between quaternary ammonium groups on the resin surface and carboxyl groups on the bacteria cell surface.
Chen et al. describe the preparation of antimicrobial dendrimers (highly-branched polymers) having quaternary ammonium functionality (Chen, et al., "Quaternary Ammonium Functionalized Poly(propylene imine) Dendrimers as Effective Antimicrobials: Structure-Activity Studies", Biomacromolecules 1 p 473-480 (2000)). The compounds described therein are soluble in water; hence, they are not suitable for use as wound dressing materials. The enhanced antimicrobial properties exhibited by polymeric quaternary compounds (relative to monomeric quats), is discussed therein, and also in several other references (Ikeda, T., "Antibacterial Activity of Polycationic Biocides", Chapter 42, page 743 in: High Performance Biomaterials, M. Szycher, ed., Technomic, Lancaster Pa., (1991); Donaruma, L. G., et al., "Anionic Polymeric Drugs", John Wiley & Son, New York, (1978); Ikeda T, Yamaguchi H, and Tazuke, S "New Polymeric Biocides: Synthesis and Antibacterial Activities of Polycations with Pendant Biguanide Groups"; Antimicrob. Agents Chemother. 26(2), p 139-44 (1984)).
U.S. Pat. No. 6,039,940, to Perrault, teaches a composition and method for treating a wound with an inherently antimicrobial dressing based on quaternary ammonium polymers. The dressing is a hydrogel containing, by weight, about 15 to 95 percent, and preferably about 61 to 90 percent, and most preferably about 65 to 75 percent, cationic quaternary amine acrylate polymer. This polymer is prepared by the polymerization of acryloyloxyethyl(or propyl)-trialkyl(or aryl)-substituted ammonium salts or acrylamidoethyl(or propyl)-trialkyl(or aryl)-substituted ammonium salts. Ultraviolet light is used as the catalyst. The antimicrobial hydrogels are stated to be non-irritating to the wound, absorb wound exudate, and, due to the inherently antimicrobial properties, "enhance the sterile environment around the wound."
However, the human trial detailed in the '940 disclosure concluded that the measured parameter, the 'irritation potential', was "not significantly different from the control". Analysis of the numerical results indicate that no hydrogel dressing tested gave a better improvement during the test period than the control. This suggests that the use of a hydrogel, although providing a "soothing effect" according to the '940 patent, may not be the optimum dressing for wound healing. Also, it is believed that the present invention offers an advantage over dressing such as the '940 dressing in that the dressing of the present invention are applied a non-gel dressings (e.g., they are dry rather than hydrated). This provides a greater potential for uptake of wound exudates and other aqueous solutions, compared to the '940 hydrogels, which already have water occupying sites in the composition.
Also, the polymers described in the '940 patent are based on acrylate or acrylamide, and as such are susceptible to hydrolysis. Hydrolysis is expected to be greater at high pH or at low pH. It should be noted that these materials are hydrogels, and thus contain a significant amount of water (e.g., 5% to 85%). It also states that the hydrogels are preferably prepared with a physical support structure in order to better retain the hydrogel over a wound. Although the possibility of forming these hydrogels around a web or fibril support is given, it is not clear that the hydrogel material is bonded to the support in any manner. The materials can be dried to powders and later reconstituted. The fact that the hydrogel materials are powders when dry would indicate that shedding of loose hydrogel particles is to be expected. A device wherein the absorbent material is permanently bound to a structural substrate would be more desirable.
The hydrogel materials described by the '940 patent are not breathable. That is, they do not permit unrestricted passage of air through the samples. In that method, the spaces between strands of the "support material" are essentially clogged by hydrated hydrogel material. In the current invention, the individual filaments and fibrils within the substrate are separately "coated" with covalently-bonded antimicrobial polymer. Note that this can be achieved even on a basic raw material such as cotton lint, or wood pulp, which can then be formed into a fabric or other useful structure. Such a process is not possible with the technology described by the '940 patent. In that case, the non-bonded composite must be formed over a prefabricated structure which is a time-consuming process.
The '940 patent also teaches that residual monomer concentrations of up to 3% are acceptable. Such a high level of residual monomer would undoubtedly result in release of active antimicrobial agent into a wound. Monomers such as those used to produce the hydrogels described in the '940 patent are known to cause skin and eye irritation, as well as sensitization (MSDS #14491: Ciba Specialty Chemicals Corporation). While not being bound to a particular theory, another source of leaching of antimicrobial activity may be poor or incomplete cross linking; this may be a source of leaching in that the polymers are only linked to one another, rather to a substrate. It is also difficult and time-consuming to completely wash a hydrogel in order to extract all residual monomer and other leachables without destroying the network structure. The leaching may become greater or less based on ambient conditions of wound exudate. Evidence of leaching from the hydrogel composition are in the '940 patent's summary of the Kirby-Bauer zone of inhibition data. That data, presented in Table 1 of the '940 patent, demonstrate large zones of inhibition, up to 20 mm, around a 5 mm square hydrogel sample. While the '940 patentees meant this data to indicate the antimicrobial effectiveness of the hydrogel, a proper interpretation, in comparison with the non-leaching attributes of the present invention, indicates that the '940 compositions demonstrate a drug-releasing/leaching phenomenon.
In conclusion with regard to the above descriptions of the art, it is apparent that there is a need for an improved dressing that has an effective antimicrobial coating or layer on it, which is covalently bound to a substrate, and is non-leaching upon use.
The antimicrobial activity of a polystyrene fiber containing covalently bonded tertiary amine groups was tested by Endo et al. ("Antimicrobial Activity of Tertiary Amine Covalently Bonded to a Polystyrene Fiber", Applied Journal of Environmental Microbiology 53(9), p 2050 (1987). Only very slight antimicrobial activity was found for these fibers in the absence of other agents. Significant antimicrobial activity was only observed when these fibers were combined with other antimicrobial agents such as deoxycholate or actinomycin (leachable antibiotics). The material described is based on polystyrene, and thus it is not expected to have physical properties suitable for an absorbent wound dressing material.
The cerium (IV) ion initiated graft polymerization of vinyl monomers onto hydroxyl-containing substrates was first described by Mino (G. Mino and S. Kaizerman; "A New Method for the Preparation of Graft Copolymers. Polymerization Initiated by Ceric Ion Redox Systems", Journal of Polymer Science 31(22), p 242 (1958)). The mechanism and kinetics of Ce(IV)-initiated graft polymerization of vinylacetate-acrylonitrile onto PVA in water solution was studied by Odian and Kho (G. Odian and J. H. T. Kho; "Ceric Ion Initiated Graft Polymerization onto Poly(vinyl Alcohol)", J. Macromolecular Science—Chemistry A4(2) p 317-330, (1970)). Later, Vitta et al. described the grafting of methacrylic acid onto solid cellulose substrates (S. B. Vitta, et al., "The Preparation and Properties of Acrylic and Methacrylic Acid Grafted Cellulose Prepared by Ceric Ion Initiation. Part I. Preparation of the Grafted Cellulose", J. Macromolecular Science—Chemistry A22(5-7) p 579-590 (1985)). None of these references describe antimicrobial materials, or graft polymers based on quaternary ammonium compounds.
A large number of other inventors have labored to produce germicidal bandage and packing materials. U.S. Pat. No. 5,441,742 to Autant et al. discloses a modified cellulosic material with biocidal properties. Unfortunately, water releases the biocidal agents from the material with the concomitant problems of irritation or toxicity towards surrounding tissues. Iodine has been a favored biocidal material. Both U.S. Pat. No. 5,302,392 to Karakelle et al. and U.S. Pat. No. 5,236,703 to Usala rely on polymers containing polyvinylpyrollidone to bind and release iodine. Another approach is shown in U.S. Pat. No. 5,091,102 to Sheridan which relies on the presence of a cationic surfactant to provide germicidal properties to a dry fabric. All of these inventions suffer the problem of having a more or less toxic germicide that can leach from the material.
All patents, patent applications and publications discussed or cited herein are understood to be incorporated by reference to the same extent as if each individual publication or patent application was specifically and individually set forth in its entirety.
From the above review, it is apparent that what is needed in the art of would dressings is a broad spectrum antibacterial or antimicrobial agent that remains in the bandage material where it can prevent bacterial growth, without exerting any negative effects on adjacent living tissue. Similarly, a need also exists for other products to have non-leaching, antibacterial or antimicrobial surfaces to act prophylactically to prevent or reduce the presence of pathogens on such surfaces. Specific examples of such applications of the present technology are provided in the following section.

This patent is subject to a terminal disclaimer.

Materials with covalently-bonded, nonleachable, polymeric antimicrobial surfaces

University of Florida Research Foundation, Inc.


A CCD scanner is provided with a regulating circuit, which stores electric-current set values of LED elements of respective colors. The regulating circuit also stores desired values corresponding to optimum light amounts of the LED elements of the respective colors. By utilizing the electric-current set value and the desired value, binary search is performed for the LED elements every color. During the binary search, the light amount of the LED element is regulated, and an electric-current value thereof is determined so as to obtain the optimum light amount. By using the determined electric-current value, the LED element is turned on to read an image.

1. Field of the Invention
The present invention relates to an image reader for reading an image recorded on a transparency of a photographic film or the like.
2. Description of the Related Art
An image reader employing an imaging device of a CCD and so forth is used for photoelectrically reading an image recorded on a transparency of a photographic film or the like. Image processing of scaling, correction processing and so forth are executed on image data obtained by the image reader. On the basis of the processed image data, an image is formed on a recording material.
In the image reader, pre-scanning and fine scanning are performed. During the pre-scanning, the image is preliminarily read for the purpose of reading the image with accuracy. During the fine scanning, the image is read under read conditions determined in accordance with density of the image.
As to a light source employed in the image reader, a conventional halogen lamp is used. Beside the halogen lamp, a light source in which LED elements are arranged is used. The LED elements emit the light of each color of red, green and blue. By employing the light source constituted of the LED elements, the device itself may be downsized. Further, there is an advantage that the lifetime of the light source is prolonged in comparison with the case of the halogen lamp.
However, when the light source constituted of the LED elements is used, mechanical performance thereof disperses in comparison with the case of the halogen lamp. Due to this, in some of the light sources, accuracy of reading the image deteriorates and readout time becomes long. Meanwhile, it is considered that a light amount of the light source is regulated by means of a volume such as a conventional analog printer employing the halogen lamp. In this case, however, it is necessary for the light source constituted of the LED elements to provide a plurality of volumes relative to the respective colors. In addition, it is also necessary to individually adjust the volumes. Thus, there arises a problem in that adjusting the volumes is troublesome.

Image reader for reading an image recorded on an original


An output buffer circuit for controlling operation of an input and output terminal utilizing a pair of MOS Transistors respectively formed in first and second wells in a substrate. The input and output terminal is connected commonly to the source of the first MOS transistor, to the drain of the second MOS transistor and to the well of the first MOS transistor in order to hold the well at the same potential as the input and output terminal. Also included is a first potential point applying a first potential to the drain of the first MOS transistor and a second potential apply commonly to the source and the well electrode of the second MOS transistor. The resulting structure controls the operating state of the input and output terminal in a manner which allows for an enhanced output potential.

1. Field of the Invention
The present invention relates to an output buffer having a pair of MOS transistors provided at a final stage.
2. Description of the Background Art
FIG. 44 is a circuit diagram showing an example of constitution of input and output circuits of a conventional semiconductor integrated circuit device with a signal level converting function.
A semiconductor integrated circuit with a signal level converting function is a semiconductor integrated circuit device having a function of converting the level of signal voltage supplied from a device operating by a supply voltage in the LSI, and outputting to an external circuit operating by a supply voltage different from the supply voltage of the circuit (internal circuit) in the LSI, and a function of converting the signal supplied by an external device of different supply voltage system into a signal level of an internal circuit, and transmitting inside.
To an input and output terminal 1, an internal circuit is connected through an input buffer 10. Through an output buffer circuit 9, the input and output terminal 1 is also connected with a control terminal 2 for receiving a control signal IN1 from the internal circuit, and an input terminal 3 for receiving an output signal IN2 from the internal circuit.
The output buffer circuit 9 comprises an input and output control circuit 6, a signal level converting circuit 7, and a buffer circuit 8a, and the control terminal 2 and input terminal 3 are connected to the input and output control circuit 6. The input and output control circuit 6 sends an output to the signal level converting circuit 7, and the signal level converting circuit 7 sends an output to the buffer circuit 8a through connection points N13, N23.
In the input and output control circuit 6 and a front half of the signal level converting circuit 7, a first supply potential VDD1 and a grounding potential GND which determine a supply voltage of the internal circuit, are applied to put them into action. On the other hand, in a rear half of the signal level converting circuit 7 and the buffer circuit 8a, a second supply potential VDD2 higher than the first supply potential VDD1 and grounding potential GND are applied to put them in action. The second supply potential VDD2 and grounding potential GND are supplied respectively from a supply potential point 4 and a grounding potential point 5.
When the control signal IN1 is at H level, the connection points N13 and N14 are respectively L level (grounding potential) and H level (second supply potential VDD2) by means of the signal level converting circuit 7, whether the output signal IN2 is at L level or H level. Consequently, both transistors Q9a and Q10 of the buffer circuit 8a are turned off, and the buffer circuit 8a comes in high impedance state relative to the input and output terminal 1. As a result, the signal from the outside given to the input and output terminal 1 is transmitted to the input buffer 10 without damage.
On the other hand, when the control signal IN1 is at L level, provided the output signal IN2 is at L level, the connection points N13 and N14 are both at L level by means of the signal level converting circuit 7. Consequently, the transistors Q9a and Q10 of the buffer circuit 8a are respectively turned off and on, so that L level is issued to the input and output terminal 1.
When the control signal IN1 is at L level and output signal IN2 is at H level, the connection points N13 and N14 are both at H level by means of the signal level converting circuit 7. Consequently, the transistors Q9a and Q10 of the buffer circuit 8a are respectively turned on and off, so that H level is issued to the input and output terminal 1.
FIG. 45 is a circuit diagram showing other example of constitution of input and output circuit of a conventional semiconductor integrated circuit device with signal level converting circuit. The constitution in FIG. 45 is similar to that in FIG. 44, except that the buffer circuit 8a is replaced by a buffer circuit 8b. In the buffer circuit 8b, inverter gate G18 and NMOS transistor Q9a in the buffer circuit 8a are replaced by a PMOS transistor Q9b.
In such constitution, too, it is evident that the operation as explained in relation to FIG. 44 is effected.
The conventional semiconductor integrated circuit devices with signal level converting function are thus constituted, and as far as the operation is normal, the set of potentials of the connection points N13 and N23 is any one of (H level and H level), (L level and L level), and (L level and H level).
However, when the first supply potential VDD1 is not applied in the initial state when the second supply potential VDD2 is turned on, the values of the parts of the signal level converting circuit 7 are not determined uniquely. For example, the set of potentials of the connection points N13 and N23 may be (H level and L level). Such status may give rise to a situation of turning on simultaneously the pair of transistors Q9a and Q10 (or Q9b and Q10), and hence flow of unnecessary current (penetration current) between the supply potential point 4 and grounding potential point 5 in the buffer circuit 8a (or 8b).
FIG. 46 is a schematic sectional view of structure of transistors Q9a, Q10 of the buffer circuit 8a. Both transistors Q9a and Q10 are of NMOS type, and are formed in P well provided with grounding potential GND.
Usually, in the NMOS transistor connected between a high potential and a low potential, the wiring is connected so that the potential of the well being formed (hereinafter called well potential) is at low potential.
However, when the well potential of the transistor Q9a is at the grounding potential GND, in the case the transistor Q9a is turned on, the potential of the source S climbs up, and a bias voltage is applied between the source S and well W.
In the absence of the bias voltage, in the case of the transistor Q9a of E (Enhancement) type, when the well potential is set to the grounding potential GND, the second supply potential VDD2 (V) is applied to the gate electrode G, and the second supply potential VDD2 (V) is applied to the drain D, the potential of the source S (input and output terminal 1) is (VDD2-VTN) (V), where VTN is the threshold voltage of the NMOS transistor Q9.
When the bias voltage is applied, on the other hand, the VTN is shifted to the positive direction to be VTN' (VTN'>VTN), and the drain current decreases. Therefore, the potential of the input and output terminal 1 becomes (VDD2-VTN') (V), and hence the output potential of H level is lower than that without the bias voltage.
FIG. 47 is a schematic sectional view showing the structure of transistors Q9b, Q10 of the buffer circuit 8b. The transistors Q9b and Q10 are respectively of PMOS type and NMOS type. Hence, the transistor Q9b is formed in the n-well provided with the second supply potential VDD2, and the well potential is set at the second supply potential VDD2. Hence, the problem caused in the transistor Q9a is avoided.


A circuit board is mounted in a cabinet in which a disk is housed. A treatment for preliminarily releasing ammonia possibly causing fogging of the disk from the circuit board is performed by allowing the circuit board to stand at 70° C. outside the cabinet for 24 hours before the circuit board is mounted in the cabinet.

FIG. 2 is a sectional view of a conventional disk recorder or player apparatus. A disk 60, which is a magneto-optical disk, is rotatably housed in a cartridge 6 having openings formed in upper and lower faces thereof. A turn table 70 and a pickup 7 movable toward and away from the turn table 70 are provided on a chassis 1 which receives the cartridge 6. A recording head 72 is attached to the pickup 7 via a head lever 71. A portion of the disk 60 is irradiated with a beam from the pickup 7 thereby to be heated at a Curie temperature and, at the same time, an upper surface portion of the disk 60 is magnetized by the recording head 72 for recording a signal therein. In signal reproduction, the disk is irradiated with a beam from the pickup 7, and the level (0-level or 1-level) of a recorded signal is determined on the basis of the diffractive direction of a light beam reflected on the disk.
The chassis 1 and the cartridge 6 are housed in a cabinet 2 constituted by cabinet halves 20, 21 which are vertically combined together. A circuit board 3 for energization of the pickup 7 and the turn table 70 is provided in the lower cabinet half 21. The circuit board 3 is composed of a glass epoxy resin or the like. It is noted that the position of the circuit board 3 is not limited to that shown in FIG. 2.
Since circuit components (not shown) mounted on the circuit board 3 generate heat during the signal recording and reproduction, the internal temperature of the cabinet 2 is liable to rise. In view of the rise of the internal temperature of the apparatus, the applicant of the present invention intends to guarantee that the apparatus normally operates at a temperature up to 70° C., and checks the apparatus to confirm that the apparatus does not malfunction at a temperature of 70° C. or lower when the apparatus is mass-produced.
The applicant found that the apparatus suffered from the following problem.
The applicant found that, when the apparatus was left at a high temperature, the surface of the disk 60 was fogged so that the C/N ratio of the reproduced signal was reduced or the disk 60 was not accurately magnetized in the recording. The applicant analyzed a substance deposited on the surface of the disk 60, and found that the major component of the substance was ammonium sulfate (NH4)2SO4. However, none of the components provided in the apparatus were produced by employing ammonium sulfate, and there was no evidence that ammonium sulfate externally adhered onto the disk.
The applicant investigated the mechanism of the generation of ammonium sulfate and, as a result, found that ammonium sulfate was generated by the following chemical reactions.
As described above, the circuit board 3 is composed of the glass epoxy resin. Further, cases of the mounted circuit components are often composed of an epoxy resin. As well known, the epoxy resin is synthesized from bisphenol-A having a molecular formula (CH3)2C(C6H4OH)2 and epichlorohydrin C3H5OCl.
Therefore, if the epoxy resin is left at a high temperature for a long period of time, bisphenol-A is decomposed and modified to undergo condensation polymerization, so that some of functional groups are removed from bisphenol-A. As a result, water and ammonia are generated as by-products. Ammonia NH3 is present in the form of molecules in a trace amount, but reacts with sulfur dioxide gas present in the atmosphere to provide ammonium sulfate (NH4)2SO4 as follows:SO2+H2O+O→H2SO4H2SO4+2NH3→(NH4)2SO4
That is, the applicant found that, where the circuit board 3 was left at around the operation guarantee temperature (70° C.) for a long period of time, ammonia is generated and, as a result, the disk 60 was fogged. With a recent trend toward the size reduction and thickness reduction of the apparatus, the cabinet 2 has a higher internal temperature. Therefore, an ammonia concentration in the cabinet 2 tends to be increased, making the disk more liable to be fogged.
It is an object of the present invention to prevent the fogging of the disk even if the disk is left at a high temperature in the apparatus for a long period of time.

Method for treating circuit board for use in disk recorder or player apparatus


Disclosed is black phosphorus or black phosphorus-carbon composite, which is very suitable for an anode material of lithium rechargeable battery. The black phosphorus or black phosphorus-carbon composite is prepared by using high energy ball-milling, which is easy and efficient way in transforming amorphous red phosphorus into orthorhombic black phosphorus at ambient temperature and pressure.

1. Field of the Invention
The invention relates to a method for preparing black phosphorus or black phosphorus-carbon composite, lithium rechargeable battery comprising the prepared black phosphorus or black phosphorus-carbon composite and method for using the rechargeable battery.
2. Description of the Related Art
Lithium ion rechargeable batteries have been used as portable power sources for a wide variety of electronic devices such as cellular phones, notebook computers and camcorders. The rechargeable batteries have lithium as its anode material and shows the very excellent performance since lithium itself has such a high energy density of 3860 mAh/g. However, when using the lithium as the anode material of the rechargeable batteries, there occurs a problem of stability reduction of the rechargeable batteries during charge. Further, there occurs a problem of low charge and discharge efficiency.
In order to solve the problems, researches on the lithium alloy has been carried out. The lithium alloy has higher energy density and larger charge and discharge capacity per weight or per volume than those of the carbon-based anode material. However, the lithium alloy still suffer from poor capacity retention since a large volume change occurs during the charge and discharge, which cause the break of the active materials and the decrease of capacity during the cycle of the battery.
Intensive researches on the silicone-based composite also have been carried out. However, such technique using silicone-based composite as the anode material of the rechargeable batteries has a problem that there is no improvement in its charge and discharge characteristics as well as its cycle characteristics even though there is an increase of the capacity during the initial cycles of the batteries.
Meanwhile, phosphorus, which is an element of the fifth group in the periodic table, has a large theoretical capacity of 2595 mAh/g so as that it can be used suitably as the anode materials of the rechargeable batteries. Phosphorus has three main allotropes i.e. white, red and black. Among these several modifications of allotropes, black phosphorus is thermodynamically the most stable, insoluble in most solvents, practically non-flammable, and chemically the least reactive form and exists in three known crystalline modifications (orthorhombic, rhombohedral and simple cubic), as well as in an amorphous form.
Since orthorhombic black phosphorus was obtained from the white one at 200° C. and 1.2 GPa in the prior art, many studies designed to synthesize black phosphorus have been carried out. However, the basic concept of a high temperature and high pressure being required in the synthesis has not been changed, and to this end it still remains difficult and inefficient to synthesize black phosphorus and to apply it commercially.

Method for preparing black phosphorus or black phosphorus-carbon composite, lithium rechargeable battery comprising the prepared black phosphorus or black phosphorus-carbon composite and method for using the rechargeable battery

Seoul National University Industry Foundation


With a view to preventing the oxidation of a metal film at the time of light oxidation treatment after gate patterning and at the same time to making it possible to control the reproducibility of oxide film formation and homogeneity of oxide film thickness at gate side-wall end portions, in a gate processing step using a poly-metal, a gate electrode is formed by patterning a gate electrode material which has been deposited over a semiconductor wafer 1A having a gate oxide film formed thereon and has a poly-metal structure and then, the principal surface of the semiconductor wafer 1A heated to a predetermined temperature or vicinity thereof is supplied with a hydrogen gas which contains water at a low concentration, the water having been formed from hydrogen and oxygen by a catalytic action, to selectively oxidize the principal surface of the semiconductor wafer 1A, whereby the profile of the side-wall end portions of the gate electrode is improved

1. Field of the Invention
This invention relates to a process for the fabrication of a semiconductor integrated circuit device, particularly to a technique effective when applied to gate processing of MOSFET (Metal Oxide Semiconductor Field Effect Transistor) having a poly-metal gate.
2. Description of the Related Art
In Japanese Patent Application Laid-Open No. H5-152282 (which will hereinafter be called "Ohmi"), disclosed is an oxide film forming device for oxidizing a semiconductor wafer or the like with water synthesized using a catalyst such as nickel.
In pages 128–133 of Papers of the Lecture addressed at the 45-th Symposium of Semiconductor Integrated Circuit Technique held on Dec. 1–2, 1992 (which will hereinafter be called "Nakamura"), disclosed is oxide film formation under a strong reducing atmosphere which contains water vapor synthesized by a stainless catalyst.
In Japanese Patent Application Laid-Open No. S59-132136 (which will hereinafter be called "Kobayashi"), disclosed is a process, in a silicon semiconductor integrated circuit device having a refractory metal (high-melting point metal) gate, for carrying out auxiliary thermal oxidation (which will hereinafter be called "light oxidation" or "auxiliary oxidation after gate formation") of not a gate metal itself but necessary portions other than the gate metal under a mixed atmosphere of water vapor and hydrogen after gate patterning, thereby adjusting an insulation film at the periphery below the gate.
Similarly, in Japanese Patent Application Laid-Open No. H3-119763 (which will hereinafter be called "Katada") and Japanese Patent Application Laid-Open No. H7-94716 (which will hereinafter be called "Muraoka"), disclosed is a process for forming a gate having a three-layered structure made of tungsten, titanium nitride and polysilicon and then subjecting it to oxidation treatment under a mixed atmosphere of hydrogen, water vapor and nitrogen.
It is presumed that for a device having a circuit formed of a minute MOSFET whose gate length is 0.25 μm or smaller, such as DRAM (Dynamic Random Access Memory) available since the development of 256 Mbit (megabit), a gate processing step using a low-resistance conductive material including a metal film will become indispensable to reduce a parasitic resistance of a gate electrode.
As such a low-resistance gate electrode material, so-called poly-metal (which generally means a refractory metal formed directly or indirectly over a polycrystalline silicon electrode) having a refractory metal film stacked over a polycrystalline silicon film is regarded as promising. The poly-metal can be used not only as a gate electrode material but also as an interconnection material because of a sheet resistance as low as 2 Ω/□. According to the investigation by the present inventors, W (tungsten), Mo (molybdenum), Ti (titanium) or the like which exhibits good low resistance even in the low temperature process not higher than 800° C. and has high electro-migration resistance is used as the refractory metal. Since the stacking of such a refractory metal film directly on a polycrystalline silicon film lowers the adhesion between these two films or happens to form a high-resistance silicide layer at the interface between these two films by a high-temperature heat treatment process, the poly-metal gate is practically formed of a three-layered structure having, between the polycrystalline silicon film and the refractory metal film, a barrier layer made of a metal nitride film such as TiN (titanium nitride) or WN (tungsten nitride).
Based on the investigation by the present inventors, gate processing is conventionally carried out as follows. First, a semiconductor substrate is thermally oxidized to form a gate oxide film on its surface Although a thermally oxidized film is generally formed in a dry oxygen atmosphere, wet oxidation is employed for the formation of a gate oxide film because a defect density in the film can be reduced. In wet oxidation, a pyrogenic method is employed in which water is formed by the combustion of hydrogen in an oxygen atmosphere and then fed to the surface of a semiconductor wafer together with oxygen.
The pyrogenic method, however, is accompanied with the drawback that combustion is effected by igniting hydrogen jetted from a nozzle attached to the tip of a quartz-made hydrogen gas inlet tube, but heat generated upon combustion melts the nozzle and generates particles, which presumably become a contamination source of a semiconductor wafer. For the formation of water, therefore, a method using a catalyst without combustion is also-proposed.
The above-described Ohmi discloses a thermal oxidation apparatus having a hydrogen gas inlet tube formed at its inside from Ni (nickel) or a Ni-containing material and being equipped with means for heating the hydrogen gas inlet tube. In this thermal oxidation apparatus, Ni (or Ni-containing material) inside of the hydrogen gas inlet tube heated at 300° C. or higher is brought into contact with hydrogen to generate a hydrogen activated species and then, the hydrogen activated species is reacted with oxygen (or an oxygen-containing gas), whereby water is generated. Water is thus generated in such a catalytic manner without combustion so that neither melting of the quartz-made hydrogen gas inlet tube at its tip point nor generation of particles occurs.
Over the gate oxide film formed by such wet oxidation method, a gate electrode material is deposited, followed by patterning the gate electrode material by dry etching with a photoresist as a mask. After the photoresist is removed by ashing treatment, the dry etching residue or ashing residue on the surface of the substrate is removed using an etching solution such as hydrofluoric acid.
By the above-described wet etching, the gate oxide film in a region other than that below the gate electrode is etched and,at the same time, the gate oxide film at the side wall end portions of the gate electrode are etched isotropically and undercuts are formed, which brings about inconveniences such as lowering in pressure resistance of the gate electrode. With a view to improving the profile having undercuts formed at the side-wall end portions of the gate electrode, the substrate is subjected to light oxidation treatment, that is, thermal oxidation again to form an oxide film on its surface.
The above-described refractory metals,such as W and Mo are considerably prone to oxidation under a high-temperature oxygen atmosphere so that the application of the above light oxidation treatment to a gate electrode of a poly-metal structure oxidizes the refractory metal film, thereby increasing its resistance or partially peeling off the film from the substrate. In the gate processing by using a poly-metal, it is therefore necessary to take countermeasures against the oxidation of a refractory metal film upon light oxidation treatment.
The above-described Kobayashi discloses a technique of selectively oxidizing Si without oxidizing a W (Mo) film by forming over a Si (silicon) substrate a gate electrode of a W- or Mo-film-containing poly-metal structure and then carrying out light oxidation in a mixed atmosphere of water vapor and hydrogen. This technique makes use of the difference between W (or Mo) and Si in a water vapor/hydrogen partial pressure ratio which brings about equilibrium in redox reaction. In this technique, selective oxidation of Si is realized by setting the partial pressure ratio within a range that W (or Mo) once oxidized by water vapor is reduced rapidly by coexisting hydrogen but Si remains oxidized. The mixed atmosphere of water vapor and hydrogen is generated by the bubbling system which feeds a hydrogen gas in pure water filled in a container and the water vapor/hydrogen partial pressure ratio is controlled by changing the temperature of the pure water.
The above-described Katada and Muraoka disclose a technique of forming a gate electrode of a poly-metal structure, more specifically, forming a metal nitride film such as TiN and a metal film such as W on a Si substrate through a gate oxide film, and then carrying out light oxidation in an atmosphere obtained by diluting a reducing gas (hydrogen) and an oxidizing gas (water vapor) with nitrogen. According to them, only Si can be oxidized selectively without oxidation of the metal film. At the same time, oxidation of the metal nitride film can be prevented, because denitrifying reaction from the nitride metal film can be prevented by diluting the water vapor/hydrogen mixed gas with nitrogen.
As described above, in the step for forming a gate electrode of a poly-metal structure, it is effective for an improvement in the pressure resistance of a gate oxide film and oxidation prevention of a metal film, to carry out light oxidation in a water vapor/hydrogen mixed gas having a predetermined partial pressure.
The conventional bubbling method which has been proposed as a method for forming the water vapor/hydrogen mixed gas is accompanied with the drawback that since the water vapor/hydrogen mixed gas is generated by supplying a hydrogen gas into pure water charged in advance in a container, foreign matters mixed in pure water are fed to an oxidizing furnace together with the water vapor/hydrogen mixed gas and presumably contaminates the semiconductor wafer.
The bubbling method is also accompanied with other drawbacks that since the water vapor/hydrogen partial pressure is controlled by changing the temperature of pure water, (1) the partial pressure ratio varies easily and the optimum pressure ratio cannot be attained with high precision, (2) the water vapor concentration on the order of ppm cannot be attained owing to the controllable range of the water vapor concentration as narrow as several to ten-odd %.
As will be described later, in the redox reaction of Si or a metal by using a water vapor/hydrogen mixed gas, oxidation tends to proceed faster when the water vapor concentration is higher. When Si is oxidized at a comparatively high water vapor concentration as the water vapor/hydrogen mixed gas formed by the bubbling system, the oxide film grows in a markedly short time owing to a high oxidation rate. A minute MOSFET having a gate length not greater than 0.25 μm is required to have a gate oxide film as thin as 5 nm or less in order to maintain the electrical properties of the device. Accordingly, it is difficult to form such a ultra-thin gate oxide film uniformly and with good controllability if the water vapor/hydrogen mixed gas generated by the bubbling method is used. When oxidation is carried out at a low temperature (for example, 80° C. or lower) to reduce the growth rate of the oxide film, a gate oxide film having good quality cannot be obtained.

Fabrication process of a semiconductor integrated circuit device


An extrusion head for at least one extruder including a first head part having a first joint and a second head having a second joint wherein the first head part and the second head part are pivotable with respect to each other using the respective first joint and second joint. When the extrusion head is in an operative position, the first head part rests against a first sealing face and the second head part rests against a second sealing face. A drive element is connected to the first head part and the second head part using a connecting element. The first head part and the second head part are movable using the drive element from a fixed operative position into an open rest position.

In practice, extrusion heads of this type are already widely used in conjunction with one or more extruders. The head parts are adapted to be moved into a rest position for the purposes of cleaning or retrofitting.
Extrusion heads for the processing of rubber mixtures require, in addition to the closed operative position, also an opened rest position in which flow ducts of the extrusion head can be exchanged or cleaned. In the operative position, the head parts have to withstand the pressure of the rubber mixture. The driving power required for pivoting the head parts into the rest position, on the one hand, and for fixing them in the closed operative position, on the other hand, is applied in this case by a plurality of drive means, in particular hydraulic cylinders.
Extrusion heads known as clamp heads, in which two lateral clamps disposed opposite one another fix the two head parts in the operative position, respectively, are already known in practice. Clamps of this type are able to absorb much greater forces than the hydraulic piston/cylinder units used to move the clamps. For this purpose, the clamps have a respective contact face forming a clamping plane, so displacement toward the side of the extrusion head facing the extruders increases the clamping forces, as disclosed by DE 22 01 631 C3 and DE-OS 22 36 363, in which the holding-together forces are absorbed by clamps which are displaced by piston/cylinder units and secured in their closed position.
It is known from that DE-OS 22 36 363 to join together the movable part and the pivotable part of a wide extrusion head, using pivotable clamps which are pressed into their clamp seat by hydraulic piston/cylinder units.
It has been found to be a disadvantage in this regard that, in order to adjust the rest position, the clamp first has to be detached by the drive means and subsequently be pivoted out of the opening region of the head parts by a further drive means.
Also already known are extrusion heads known as hammer heads, in which each of the head parts has associated therewith two respective external, substantially parallel tension elements, of which a tension element head engages a corresponding recess in the respective head part in the operative position, thereby allowing the required pressure force to be applied by the tension elements.
DE 42 36 120 C1 has already described an extrusion head of this type for an extrusion system in the rubber or plastics processing industry, comprising a stationary head part which is to be flanged onto the extrusion system and at least one head part which rests against the extrusion strip, can be pivoted for cleaning purposes and is hingedly attached to the stationary head part by a joint. In the operative position, the head parts are for this purpose clamped to the stationary part by a pair of tie actuated by a respective piston/cylinder unit, and can be pivoted into the rest position by a further piston/cylinder unit.
DE 34 30 062 C2 and, in another embodiment, DE 37 36 231 A1 also disclose a respective extrusion head in which the movable parts of the extrusion head apply the high closing forces required, merely by means of piston/cylinder units. This necessitates the use of very powerful piston/cylinder units.
In the case of DE 34 30 062 C2, one end of the piston/cylinder unit is hingedly attached to the stationary part of the extrusion head in an outwardly pivotable manner. During the opening process, the piston/cylinder unit is pressed outward under the influence of this link, so the tie rods are pivoted out of the path of movement of the pivotable extrusion head parts to allow the opening thereof.
In addition, DE-OS 24 57 532 discloses a single extrusion head with two movable head halves, the common parting plane of which passes through the axis of the extruder, each two movable head halves forming a further parting plane or pair of pressure faces against the end face of the extruder. In this known extruder, a respective hydraulic cylinder is hingedly attached to the cylinder of the screw-type extruder centrally at the top and bottom, the piston rod of each hydraulic cylinder on a double lever having the function of releasing and fixing the cartridge and the profile strip and of opening, closing and fixing the head parts. Apart from the fact that this closing system is limited to an extrusion head with two movable head parts, clamps have to be pivoted to the side to open and close the head parts of this extrusion head also.
In any case, the tension frames have to be pivoted out to the side when the movable head parts are to be raised or lowered to open the feed ducts. However, the pivoting-out of the tension frames, which are already very wide, to the side, requires a large amount of space. In addition, the hydraulic cylinders, which are likewise pivotable for this purpose, have to be connected to a pressure source via flexible lines.
Also known is a construction in which the head parts are pivotably movable in the conventional manner about joints disposed on either side of a longitudinal axis, by means of a single drive means associated with the respective head part. The drive means, which are constructed as hydraulic cylinders, have the function in this case of transmitting the holding force and the sealing forces in the operative position and also of pivoting into the rest position and are for this purpose disposed substantially at right angles to the longitudinal axis. The resulting much greater dimensions have been found to be a disadvantage in this regard.
DE 39 23 290 C1 relates to an extruder head for producing profiles which are made of diverse mixtures of rubbers and/or plastics materials and are extruded from a plurality of extruders, with at least one movable head part. In this case a drive means has the function of generating the closing force for pressing the main parts together and also acts as a wedge-shaped locking device having clamps.


A method for generating power from an exerted energy associated with muscles acting across a joint is provided. The method including: absorbing energy during one or more periods of a periodic motion of the joint in which energy is absorbed by the muscles; and at least partially returning the absorbed energy to one of an energy storage device or power consuming device.

1. Field of the Invention
The present invention relates generally to walk-assist and power generation devices and methods, and more particularly, to devices, which generate power and/or assist movement when worn.
2. Prior Art
During walking on a flat, rigid and horizontal surface, a human subject spends energy and tires. On the other hand, if the human subject were instead riding a bicycle that is in good condition, the subject has to spend a significantly less amount of energy to travel the same amount of distance. And in general, the faster the person walks (or runs), the difference between the amount of energy that has to be spent to travel a certain distance on foot or on bicycle becomes greater. The reason for this significant difference in the amount of energy that a person has to spend to travel a certain amount of distance can be described as follows. Here, the objective is to account for the major sources of energy expenditure and for the secondary and generally less significant but complex processes that demand energy expenditure during locomotion.
During normal walking (gait), there are two main sources of energy expenditure. Firstly, due to the structure of the human body, energy is spent to sequentially accelerate and decelerate the lower limbs and to a lesser degree certain other parts of the body (e.g., pumping arms) to achieve locomotion. This component of the energy spend by a person during the process of locomotion is hereinafter called the "locomotion energy". This is the case even during a highly efficient mode of locomotion along a straight path in which the trunk moves at a nearly constant velocity. During normal walking, the motion of the lower limb is nearly periodic. During each cycle of gait, the muscles acting on the lower limbs are responsible for both accelerating and decelerating the limb segments. The muscles consume energy to apply the forces required to accelerate the limb segments and they consume energy to apply the forces required to decelerate the limb segments. In comparison, if the person were riding a bicycle, following initial acceleration to a constant travel velocity, the person has to provide minimal energy to the human-bicycle system since no significant inertia has to be sequentially accelerated and decelerated (neglecting the small friction forces, aerodynamic drag, etc.).
Secondly, muscle forces have to provide the required forces across the various joints of the lower extremities and the back and neck to keep the body upright (or on the seat of the bicycle) and to provide for a stable posture. Thereby the person has to spend energy to provide such muscle forces. This component of the energy spent by a person during the process of locomotion is hereinafter called the "stance energy". The amount of energy required for this purpose is usually significantly higher than the required minimum since the muscle groups generally act together and provide opposing (isometric) forces that provide joint preloads that in turn provide for extra stability margin.
Thus, in order to more significantly reduce the amount of energy that a person has to spend during locomotion, the amount of aforementioned "locomotion energy" and "stance energy" that is consumed by the muscles has to be reduced. Currently, certain devices are known in the art that are used to reduce joint loads and/or to reduce muscle forces (mostly in the lower extremities) that are required for stance stability. These devices do reduce the "stance energy", some a very small amount and some slightly more, and are discussed below. There is, however, no device currently available for directly reducing the "locomotion energy".
To provide or supplement muscle forces in achieving a stable stance, various assist or support devices have been developed. Such stance or support assist devices generally help to reduce the muscle forces that are required to keep the body upright and to provide stance (sitting) stability. As a result, such devices also help reduce the aforementioned "stance energy" requirements during locomotion to various degrees. A person may use one or more of such assist or support devices due to the lack of adequate muscle force levels or control due to age, joint disease, soft or hard tissue injury or operation, etc. These devices include various braces, walkers, canes, crutches, and the like. As a result, the forces that the muscles have to provide and the forces across the various joints of the lower extremities are generally reduced. The currently available assist devices may be divided into the following two categories. Here, various shoe inserts, components incorporated into the shoes, etc., are not considered since they are primarily used to modify force distribution on the foot and its joints by providing certain type of interface between the foot and the shoe (ground).                1. Various bracing devices used to bridge one or more joints, for the primary purpose of reducing the load transmitted through the joint. The level of muscle forces that act across the joint to provide joint stability is also reduced, thereby further reducing the joint forces. Depending on the effectiveness of the bracing in providing joint (stance) stability, the "stance energy" is reduced by a certain amount.        2. Various walk assist devices such as walkers, canes, crutches, etc., for the primary purpose of reducing load on one or both lower extremities. When such assist devices are used, other muscles, usually the arm and shoulder and certain upper body muscles, must then provide the forces needed to assist stance stability and locomotion. The person obviously has to spend energy to provide the latter muscle forces. The currently available assist devices do not significantly reduce the total stance energy expended but merely transfer the load from the lower limb muscles to the muscles of the arm and the upper body.

Method for generating power across a joint of the body during a locomotion cycle


A process to determine the porosity and/or mineral content of mineral samples with an x-ray CT system is described. Based on the direct-projection techniques that use a spatially-resolved x-ray detector to record the x-ray radiation passing through the sample, 1 micrometer or better resolution is achievable. Furthermore, by using an x-ray objective lens to magnify the x-ray image in a microscope configuration, a higher resolution of up to 50 nanometers or more is achieved with state-of-the-art technology. These x-ray CT techniques directly obtain the 3D structure of the sample with no modifications to the sample being necessary. Furthermore, fluid or gas flow experiments can often be conducted during data acquisition so that one may perform live monitoring of the physical process in 3D.

X-ray imaging, including projection and microscopy techniques, have been widely used in medical imaging and industrial inspection since their invention. A particularly important development is the computed tomography (CT) techniques that allow the three dimensional (3D) structure of a sample to be reconstructed from a series of two dimensional (2D) x-ray images acquired at different view angles. Furthermore, recent advances in micro x-ray CT has pushed the 3D resolution to 1 micrometer with direct-projection type imaging systems, while using x-ray objective lenses, such as Fresnel zone plates, 3D images with up to 50 nanometer resolution have been demonstrated.
Mineral samples analysis for mining is important as ores are used in metal production and crude oil extracted from bituminous sand and coal provide a substantial proportion of our energy consumption. Understanding the structure of the mineral samples is therefore important for using them effectively and locating mining operations. This often involves examining the porous structures in the sample. Traditionally, this is usually accomplished with indirect measurements such as running fluid through the sample and measuring the flow rate under different pressures. Any imaging techniques are often destructive involving lapping and polishing the sample and then imaging with light microscope or scanning electron microscope.

Process for examining mineral samples with X-ray microscope and projection systems


A multi-layer knee pad construction 10 for attachment to the interior surface 102 of the knee portion 101 of a pair of pants 100. The construction 10 includes an outer waterproof layer 11, an inner low friction layer 13 and an intermediate padded layer 12 operatively connected to one another and the interior surface 102 of the pair of pants by a plurality bonding layers 14.

1. Field of the Invention
The present invention relates to the field of protective padding devices in general, and in particular to a multi-layer knee pad construction.
2. Description of Related Art
As can be seen by reference to the following U.S. Pat. Nos. 4,831,666; 4,920,577; 5,134,726; and 5,592,689, the prior art is replete with myriad and diverse protective knee pad constructions.
While all of the aforementioned prior art constructions are more than adequate for the basic purpose and function for which they have been specifically designed, they are uniformly deficient with respect to their failure to provide a simple, efficient, and practical protective knee pad construction that can be ironed onto the interior knee portion of a pair of pants to provide a low profile waterproof, cushioned knee pad construction.
As any gardener, construction worker, or parent with small children is all too well aware, the presence of a protective knee covering is an absolute necessity under virtually all circumstances.
As a consequence of the foregoing situation, there has existed a longstanding need for a new and improved type of knee pad construction that employs a multi-layer construction that is waterproof, cushioned, and low friction, and the provision of such a construction is a stated objective of the present invention.


A reaction propulsion motor (200) utilizes a taut armature reciprocating impulse transducer (100) having a motional mass (18) to generate an excitation force in response to an excitation signal. A conveyor element (204) translates the excitation force into locomotion. A transmission medium (202) is coupled between the taut armature reciprocating impulse transducer (100) and the conveyor element (204) to couple the excitation force generated to the conveyor element (204).

Prior art linear motors required rotors and stators, wherein the stator was part of a track on which the rotor traveled to produce locomotion. Thus the prior art linear motors were not capable of being used, except by providing a track which guided the linear motor between locations.
Thus what is needed is a linear motor which can provide locomotion without the use of a track or guide.

Reaction propulsion motor and apparatus for using the same


A hybrid drive device in which an input shaft is connected to an engine, an output shaft is connected to wheels, and a wheel drive motor is connected between the input shaft and the output shaft. In the hybrid device, a friction engagement element that is provided between the input shaft and the output shaft and of which transfer torque is controllable. A control device controls the friction engagement element. The control device reduces the transfer torque of the friction engagement element during engine starting in a predetermined low temperature environment or during travel on a bad road, compared to the transfer torque of the friction engagement element in an engaged state.

There has hitherto been known a hybrid drive device of this type (see Patent Document 1, for example). In the configuration disclosed in Patent Document 1, a friction engagement element (torque limiter) of fixed transfer torque is provided between an input shaft and an output shaft. The torque limiter functions to protect various portions of a drive transfer mechanism of the hybrid drive device from excessively large torque by slipping when torque that is equal to or more than predetermined torque (upper-limit torque) is transferred to the drive transfer mechanism so that torque that is equal to or more than the predetermined torque is not transferred to the various portions of the drive transfer mechanism.


A system and process for modeling attributes of a set of observed data. The system and process may include an initialization process providing for a likelihood function, a first order prior function; a calibration data set; a flexible interface module in which the likelihood function, the first order first order prior function, and the second order prior function are written in a programming language; a parameter bounding process in which parameters determined to be too large are interpolated or sequentially locked down; an outlier flagging process which identifies outliers using the gradient of the likelihood function; and an output process which reports information that may include outlier forces, confidence intervals, and other factors that are unique to this modeler and useful in refining the model.

Practical application in business has been found for numerical modeling techniques in permitting businesses to make decision and take actions that can enhance revenue, market share, and other desirable objectives. Construction of detailed business models has been made more feasible by the availability of more detailed empirical observations from sources such as, for example, point of sale devices that can capture detailed information not previously available. There exists a need, therefore, for new approaches to analyze this available information in order to make better informed decisions. Innovations as described in this application have been found to render such modeling efforts comparatively more effective than models constructed without benefit of these teachings, as has been reflected in commercial success these innovate techniques have enjoyed in comparison with other less effective techniques against which they compete. The innovations described herein are being used to enable businesses to increase profits, increase sales volume, increase market share, improve risk profiles, manage strategic goals, and forecast more accurately quantities such as profit and origination volume.
Parameter estimation is conceptually simple. Data are observed empirically in the realm to be modeled for variates believed to be correlated. A form of function is postulated, the function being characterized by a set of parameters. Parameter estimation is a process for calculating, determining, or otherwise estimating those parameters characterizing that correlation function so as to minimize in some sense the difference between values predicted by the correlation function and values observed empirically.
Although parameter estimation is conceptually simple, many practical factors make the process more complicated. Many theoretical solutions to the problem of parameter estimation are known for those circumstances where data are well-behaved in adhering to conventional parametric statistics. But in the real world, various circumstances often encountered in empirically observed data often limit the effectiveness of these theoretically sound processes. Practical factors complicating parameter estimation include: lack of information, co-linearity, heteroskedacity, over-dispersion, bad data, and serial correlation.
One factor which may complicate parameter estimation in practice is a lack of useful information. Where, for example, the empirical data describes, for example, sales history, the price of an item may have never changed leading to no information about the price elasticity. In standard regression analysis this would produce an indeterminate matrix. This is a consequence of the fact that this empirical data is a record of observations, not the result of experimental design. Circumstances in general over the period of time observed may never have presented variations for which in theory one would prefer to have empirical observations.
Another factor which may complicate parameter estimation is co-linearity in factors. Factors here refers to those elements of the empirically observed data that are considered to be inputs in the correlation function. For example, it may be desired to model sales rate, volume, or quantity as a function of factors including item price and promotional efforts. In the empirically observed data, it may occur that the price changes at essentially the same time that the item is put on promotion. A practical problem in conventional parameter estimation is how to know how much of any change in sales is attributable to the price drop and how much is attributable to the promotional efforts. Such colinearity leads to a similar problem in conventional analysis as would the lack of information discussed above.
Another factor which may complicate parameter estimation is heteroskedacity. The term heteroskedacity denotes the effect that errors in observations may change with each measurement. For example, in sales data the error estimate associated with a promotional event may be much higher than the error estimate associated with a regular sales event. In general, the error estimates for observations at key points in the data set for which it is desired to construct an attribute model may not be the same as the error estimates for observations in other parts of the data set.
Another factor which may complicate parameter estimation is over-dispersion in the distribution characterizing data empirically observed. It has been found in practice that many naturally occurring distributions do not follow simple and conventional known distributions such as, for example, a Gaussian distribution or Poisson distributions. Instead, distributions observed in practice may be over-disperse or may present wider tails than would be expected with simple distributions.
Another factor which may complicate parameter estimation is bad or incomplete data. For example, where empirically observed data models events such as product sales, a strong spike in sales can have a strong influence on the parameter estimates Such a strong spike may occur in the empirically observed data at essentially the same time as some change in the attribute being modeled, but that similarity in time may be entirely coincidental. The spike in sales could instead have been cased by some other factor for which the model has no visibility. Such coincidental variation can clearly cause a problem in the model. In practice, one technique used to try to minimize the effects of such bad or incomplete data is to filter outliers before modeling. However, indiscriminate filtering of outliers can cause valuable information to be wrongly classified as outliers and discarded. Those outliers may correspond to points in the model in which one is most interested. There is a need, therefore, for a more intelligent and principled way to identify outliers less arbitrarily.
Another important factor which may complicate parameter estimation is serial correlation. Data empirically observed may be a function of time, reflecting trends, seasonality, and periodicity. In general, data observed may be in part a function of previously observed data. What happened yesterday may a good indicator of what will happen today.
Parameter estimation, while conceptually simple, thus becomes a very challenging problem due to these practical issues. While there is commercial software available to estimate model parameters, products now available in general do not sufficiently productize this process. Existing approaches using known, commercially available software typically require a sophisticated analysis from a highly qualified individual analyst (typically a person having a doctorate in a relevant field) to "build the model". Building the model is a process where the analyst reviews and tweaks the model based on intuition and an understanding of potential parameter estimation problems. Building the model is not a scalable process for large enterprises that are required to manage millions of models. For example, a retailer may have hundreds of thousands of products that are sold in thousands of stores throughout the world, corresponding to hundreds of millions of individual product models which must be managed.
In many attribute models as currently practiced a single parameter is employed to model the equation. That parameters is usually postulated to adhere to some parametric distribution, such as a Gaussian, Poisson or Student T distribution. There exists a need therefore for a modeling framework for analyzing business problems and the like in which the parameters are not limited to one dimension. There further exists a need for a modeling framework for analyzing business problems and the like in which the model is not restricted to a linear form or the assumption of a particular parametric distribution.
Recently, there has been a strong interest in "Bayesian-Shrinkage". Bayesian shrinkage is a statistical technique that essentially shrinks or pulls a parameter value towards its average. Bayesian-Shrinkage helps to reduce the problems associated with lack of information and co-linearity when one has a good external estimate for a parameter. However, it is frequently the case that one does not have a good external estimate for a parameter. Furthermore, "Bayesian-Shrinkage" does not incorporate knowledge concerning (or otherwise take advantage of) relationships between parameters. Often, the analyst or other individual seeking to model empirically observed data may know or suspect some functional relationship between or among parameters. This expectation of a functional relationship may be based on factors such as intuition, experience, or knowledge of physical laws showing that there is some functional relationship between parameters. Current applications provide no way of providing this information to the parameter estimation process. Also, Bayesian-Shrinkage does not help with bad data that tend to throw parameters to unrealistically extreme values. There exists a need, therefore, for an attribute modeler better able to overcome these problems that exist in known approaches to the attribute modeling.
The term outliers denotes unlikely events that can bias parameter estimates. Outliers are anomalies that need to be removed from the modeling data set. Typically in systems in use today outliers are flagged based on a Gaussian distribution. If the data point is more than N standard deviations from the mean it is flagged as an outlier and eliminated from the modeling data set. Unfortunately, this simple process may eliminate much of the important data for certain applications, such as modeling sales data. Using this criteria of deviation from a Gaussian distribution, most promotional events would be classified as outliers and eliminated. There exists a need, therefore, for a better way to identify outliers in an attribute modeler.


An electronic endoscope system which includes a device for detecting an image, and a device for inputting an information signal. The image detecting device outputs an electrical image signal, which is converted to an analog video signal and a digital video signal. The digital video signal is combined with the information signal by an image combining device, to form a digital information signal. The digital information signal is serially outputted to a device which displays the image data in accordance with the outputted serial digital information signal. The digital information signal is also serially outputted to a device which reproduces the information signal in accordance with the outputted serial digital information signal.

The present invention relates to an electronic endoscope system which detects an image of an object using an imaging device, processes the detected image, and outputs the processed image to a monitor for viewing.
In the conventional electronic endoscope system, an image of an object (such as internal organ or tract of the human body) is formed by an optical system on an imaging device, such as a CCD. The imaging device outputs an electrical signal to a video processor. The video processor processes the signals and outputs an analog RGB signal, a composite video signal and an S video signal. The composite video signal and S video signal are then inputted to a monitor in order to display the image detected by the electronic endoscope system.
Recently, for medical studies, there has been a need to remotely observe images detected by an electronic endoscope system, in real time. If the conventional electronic endoscope system is employed, the analog video signals output by the video processor must be transmitted to the monitor at the remote location. If the distance of the remote location from the electronic endoscope system is great, then due to transmission loss, the quality of the image displayed on the monitor will degrade to an unacceptable level.
Further, in the conventional electronic endoscope system, information related to the name of the patient, the current date and time, and comments by the medical personnel are displayed on the monitor. However, data related to an operation of the electronic endoscope system and data related to the type of image processing are only indicated on the video processor. Therefore, if the image is being observed on a monitor at a remote location, it is not possible to display all the information related to the current status of the electronic endoscope system.

Electronic endoscope system with information combined in digital output