Disclosed are methods for sterilizing cyanoacrylate prepolymer compositions under visible light irradiation conditions wherein the prepolymer remains in polymerizable form after sterilization.

This invention is directed to methods for sterilizing cyanoacrylate propolymer compositions under conditions wherein the prepolymer remains in polymerizable (non-gelled) form after sterilization. The methods of this invention employ, in part, visible light irradiation sterilization techniques.
The following patent applications and patents are cited and/or referenced in this application as superscript numbers:
1 Hawkins, et al., Surgical Adhesive Compositions, U.S. Pat. No. 3,591,676, issued on Jul. 6, 1971
2 Halpern, et al., Adhesive for Living Tissue, U.S. Pat. No. 3,667,472, issued on Jun. 6, 1972
3 McIntire, et al., Process for the Preparation of Poly(xcex1-Cyanoacrylates), U.S. Pat. No. 3,654,239, issued on Apr. 4, 1972
4 Barley, et al., Methods for Treating Non-Suturable Wounds by Use of Cyanoacrylate Adhesives, International Patent Application Publication No. WO 93/25196, published on Dec. 23, 1993
5 Barley, et al., Methods for Treating Suturable Wounds by Use of Sutures and Cyanoacrylate Adhesives, U.S. Pat. No. 5,254,132, issued on Oct. 19, 1993
6 Barley, et al., Methods for Reducing Skin Irritation From Artificial Devices by Use of Cyanoacrylate Adhesives, U.S. Pat. No. 5,653,769, issued on Aug. 5, 1997
7 Rabinowitz, et al., Method of Surgically Bonding Tissue Together, U.S. Pat. No. 3,527,224, issued on Sep. 8, 1970
8 Kronenthal, et al., Surgical Adhesives, U.S. Pat. No. 3,995,641, issued on Dec. 7, 1976
9 Davydov, et al., Medical Adhesive, U.S. Pat. No. 4,035,334, issued on Jul. 12, 1977
10 Waniczek, et al., Stabilized Cyanoacrylate Adhesives Containing Bis-Trialkylsilyl Esters of Sulfuric Acid, U.S. Pat. No. 4,650,826, issued on Mar. 17, 1987
11 Askill, et al., xe2x80x9cMethods for Draping Surgical Incision Sitesxe2x80x9d U.S. Pat. No. 5,730,994 issued on Mar. 24, 1998
12 Stehlik, xe2x80x9cSterilisation of Tissue Binding Adhesivesxe2x80x9d, British Patent Application Publication No. 1 281 457, published on Jul. 12, 1972
13 McDonnell, et al., xe2x80x9cSterilized Cyanoacrylate Adhesive Composition, and a Method of Making Such a Compositionxe2x80x9d, U.S. Pat. No. 5,530,037, issued on Jun. 25, 1996
14 Greff, et al., xe2x80x9cCyanoacrylate Adhesive Compositionsxe2x80x9d, U.S. Pat. No. 5,480,935, issued on Jan. 2, 1996
15 Askill, et al., xe2x80x9cPackage for Cyanoacrylate Compositionxe2x80x9d, U.S. patent application Ser. No.09/062,514, filed on Apr. 17, 1997
16 O""Sullivan, et al., High Viscosity Cyanoacrylate Adhesive Compositions, and Process for Their Preparation, U.S. Pat. No. 4,038,345, issued on Jul. 26, 1977
17 Joyner, et al., Plasticized Monomeric Adhesive Compositions and Articles Prepared Therefrom, U.S. Pat. No. 2,784,127, issued on Mar. 5, 1957
18 Columbus, et al., Adhesive Cyanoacrylate Compositions with Reduced Adhesion to Skin, U.S. Pat. No. 4,444,933, issued on Apr. 24, 1984
19 Greff, et al., xe2x80x9cCyanoacrylate Compositions Comprising an Antimicrobial Agentxe2x80x9d, U.S. Pat. No. 5,684,042, issued on Nov. 4, 1997
20 Kotsev, British Patent Application Serial No. 2 306 469A, xe2x80x9cSterilizing Cyanoacrylate Preparationsxe2x80x9d published May 7, 1997
21 Greff, et al., U.S. Pat. No. 6,248,800, Methods for Sterilizing Cyanoacrylate Compositions, issued on Jun. 19, 2001
22 Hickey, et al., U.S. Pat. No. 6,143,805, Electron Beam Sterilization of Liquid Adhesive Compositions, issued on Nov. 7, 2000
All of the above patent applications and patents are herein incorporated by reference in their entirety to the same extent as if each individual patent application or patent was specifically and individually indicated to be incorporated by reference in its entirety.
Compositions comprising cyanoacrylate esters have been disclosed as having adhesive properties suitable for a variety of human medical uses. Such uses include, for example, use as a replacement or adjunct for sutures or staples in closing the dermal layer of an incision after surgery; use as a hemostat; use in covering small non-suturable wounds on skin surfaces; use in inhibiting surface skin irritation arising from friction between the skin surface and artificial devices such as tapes, prosthetic devices, casts, etc.; and use in the in situ formation of a surgical incise drape.1-6, 11
In each case, when topically applied to mammalian skin, the cyanoacrylate rapidly polymerizes, typically within a minute, to form a coherent, adhesive, polymeric film which strongly adheres to the skin.
Cyanoacrylate esters suggested for such uses include the following structures:
wherein R is an alkyl or other suitable substituent. Such cyanoacrylate esters are disclosed in, for example, U.S. Pat. Nos. 3,527,224; 3,591,676; 3,667,472; 3,995,641; 4,035,334; and 4,650,826.1,2,7-10
In view of the numerous medical uses of cyanoacrylate ester compositions, sterilized forms of these compositions would be particularly beneficial. In fact, it would be particularly desirable if the sterilization techniques were conducted on the packaged product so that, upon sterilization, the sterilized composition could be immediately shipped. Sterilization of the packaged product would thereby prevent reintroduction of microbial contaminants during the packaging step.
However, when applied to cyanoacrylate ester compositions, conventional sterilization techniques are often unsuitable or suffer from undesirable results. For example, it is essential that the selected sterilization technique employed does not cause in polymerization of the cyanoacrylate ester and, accordingly, high temperature heat or steam sterilization techniques are often contra-indicated, although Dimiter20 reports the use of heat sterilization temperatures of at least 160xc2x0 C. for these compositions. Similarly, when sterilization is conducted on packaged cyanoacrylate ester compositions, selected sterilization methods must be able to penetrate the packaging material and sterilize the entire contents of the package including the cyanoacrylate ester composition.
In point of fact, Stehlik12 recites that normal sterilization processes such as steam-sterilization, heat sterilization, gas treatment, sterile filtration and ionizing radiation at room temperature are unacceptable because these processes result in polymerization of the cyanoacrylate ester leading to solid compositions unsuitable for use as adhesives. Stehlik goes on to disclose that sterilization of cyanoacrylate compositions can be preferably achieved by first solidifying the composition by freezing the composition at very low temperatures (xe2x88x92196xc2x0 C. and 80xc2x0 C. being disclosed in the examples) and then exposing the frozen, solidified composition to xcex3-ionizing radiation. In this reference, radiation doses of, e.g., 1.5 mRad of Co60 xcex3-radiation, were disclosed as killing bacterial spores.
It is apparent, however, that the use of low temperatures to achieve solidification of the cyanoacrylate ester composition is not practical for manufacture on an industrial scale.
McDonnell, et al.13 also recite that most sterilization methods are unsuitable or suffer severe limitations in their applicability to cyanoacrylate compositions and, in particular, packaged cyanoacrylate compositions. In fact, this reference discloses that sterilization via electron beam (E-beam) exposure is unacceptable because E-beam accelerators have relatively low penetrating ability and would be effective only in sterilizing the outer surfaces of the package. McDonnell, et al. then recites sterilization techniques using a very high dose of xcex3-irradiation (at least 2.5 mRad) delivered to the composition at room temperature.
Notwithstanding McDonnell, et al.""s disclosure, several references disclose successful sterilization of cyanoacrylates using E-beam techniques. See, for example, Greff, et al.21 and Hickey, et al.22
However, E-beam sterilization techniques require specialized instrumentation which is very expensive and has limits on its penetrating abilities as described by Greff, et al.21 Moreover, installation and operation of such instrumentation is neither practical not cost effective for most manufacturing companies. Devises sterilized by E-beam are typically shipped away to a dedicated facility leading to significant cost and production delays. Accordingly, more accessible and cost effective techniques for cyanoacrylate sterilization would be beneficial.
This invention is directed to methods for sterilizing cyanoacrylate ester compositions. In particular, this invention is directed to the novel and unexpected result that, under carefully controlled conditions, cyanoacrylate ester compositions can be sterilized using visible light irradiation at room temperature conditions.
In a particular aspect, it has been discovered that employing a sufficiently energetic visible light source allows for sterilization of polymerizable cyanoacrylate ester compositions without significant polymerization of these compositions.
Accordingly, in one of its method aspects, this invention is directed to a method for preparing a polymerizable, sterile, cyanoacrylate ester composition wherein the method comprises exposing a polymerizable cyanoacrylate ester composition to a sufficient dosage of visible light irradiation under conditions wherein the cyanoacrylate ester composition is sterilized without gelling the composition.
In a preferred embodiment, the polymerizable cyanoacrylate ester is a polymerizable monomer or reactive oligomer of a cyanoacrylate ester. Such monomers and reactive oligomers are sometimes referred to herein simply as xe2x80x9cprepolymersxe2x80x9d and, in monomeric form, are preferably represented by formula I:
wherein R is selected from the group consisting of:
alkyl of 1 to 10 carbon atoms,
alkenyl of 2 to 10 carbon atoms,
cycloalkyl groups of from 5 to 8 carbon atoms,
phenyl,
2-ethoxyethyl,
3-methoxybutyl,
and a substituent of the formula:
wherein each Rxe2x80x2 is independently selected from the group consisting of:
hydrogen and methyl, and
Rxe2x80x3 is selected from the group consisting of:
alkyl of from 1 to 6 carbon atoms,
alkenyl of from 2 to 6 carbon atoms,
alkynyl of from 2 to 6 carbon atoms,
cycloalkyl of from 3 to 8 carbon atoms,
aralkyl selected from the group consisting of benzyl, methylbenzyl and phenylethyl,
phenyl, and
phenyl substituted with 1 to 3 substituents selected from the group consisting of hydroxy, chloro, bromo, nitro, alkyl of 1 to 4 carbon atoms, and alkoxy of from 1 to 4 carbon atoms.
More preferably, in the cyanoacrylate esters of formula I, R is alkyl of from 2 to 10 carbon atoms and still more preferably alkyl of from 4 to 8 carbon atoms. Even more preferably, R is butyl, pentyl or octyl and most preferably, R is n-butyl.
In another preferred embodiment, the cyanoacrylate ester composition is formulated to contain an effective amount of a mixture of a biocompatible acid polymerization inhibitor and a biocompatible free radical polymerization inhibitor to inhibit polymerization of the cyanoacrylate ester and an effective amount of a biocompatible plasticizer.
The preferred mixture of polymerization inhibitors is a biocompatible acid polymerization inhibitor such as sulfur dioxide, glacial acid and other well known acid polymerization inhibitors and a biocompatible free radical polymerization inhibitor including hydroquinone and hindered phenols (e.g., 4-methoxyphenol). The acid polymerization inhibitor is preferably SO2 which is preferably employed at from about 50 to 1000 ppm, more preferably from about 50 to 500 ppm, and even more preferably from about 200 to 500 ppm, based on the total weight of the composition. The free radical inhibitor is preferably hydroquinone which is preferably employed at a concentration of from about 50 to 250 ppm and more preferably at about 150 ppm. In a particularly preferred embodiment, the polymerization inhibitor is selected such that it does not form decomposition products on exposure to visible light irradiation which are toxic or irritating to mammalian skin or which cause premature polymerization or prevent the polymerization of the cyanoacrylate ester composition.
Preferred biocompatible plasticizers are dioctyl phthalate and/or acetyl tri-n-butyl citrate which are employed in sufficient amounts to enhance the flexibility of the resulting polymeric cyanoacrylate film. Again, in a particularly preferred embodiment, the biocompatible plasticizer is selected such that it does not form decomposition products on exposure to visible light irradiation which are toxic or irritating to mammalian skin or which cause premature polymerization or prevent the polymerization of the cyanoacrylate ester composition.
In another preferred embodiment, the cyanoacrylate ester composition further comprises a compatible antimicrobial agent and even more preferably an antimicrobial complex of iodine molecules with a biocompatible polymer. Such complexes include the commercially available povidone iodine which can be mixed with the cyanoacrylate composition prior to visible light sterilization or can be included as a separate component (e.g., a two component system) in the packaged cyanoacrylate composition wherein the cyanoacrylate component is sterilized by visible light irradiation.
The methods of this invention are particularly beneficial when the cyanoacrylate composition to be sterilized is in a packaging element. In this aspect, this invention is directed to a method for preparing a polymerizable, sterile, cyanoacrylate ester composition in a packaging element wherein the method comprises:
(a) selecting a packaging element which is transparent to visible light irradiation;
(b) adding a cyanoacrylate ester composition to the packaging element selected in (a) above; and
(c) exposing the packaging element formed in (b) above to a sufficient dosage of visible light irradiation to sterilize both the packaging element and the cyanoacrylate ester composition therein without gelling the composition.
In still another of its method aspects, this invention is directed to a method for preparing a polymerizable, sterile, cyanoacrylate ester composition in a packaging element wherein the method comprises:
(a) selecting a packaging element in the form of an ampule having a neck portion configured for heat sealing after fill wherein said packaging element is transparent to visible light irradiation;
(b) exposing said ampule to a sufficient amount of a sanitizing agent to reduce the level of bioburden on the ampule;
(c) selecting a polymerizable cyanoacrylate ester composition;
(d) filtering said cyanoacrylate ester composition through a biofilter having a maximum pore size of less than about 1 micron;
(e) adding the filtered cyanoacrylate ester composition to the ampule prepared in (b) above;
(f) sealing the ampule prepared in (e) by heat sealing the neck portion of said ampule;
(g) combining ampules produced in (f) above into a set of ampules;
(h) sealing the set of ampules formed in (g) above with a secondary sealing means so as to form a packaging element comprising said set of ampules; and
(i) exposing the packaging element formed in (h) above to a sufficient dosage of visible light to sterilize both the packaging element and the cyanoacrylate ester composition therein without solidifying or gelling the composition.
Preferred sanitizing agents include, for example, heat, plasma and ethylene oxide gas.
This invention is directed, in part, to methods for sterilizing cyanoacrylate prepolymer compositions with visible light irradiation wherein the prepolymer remains in polymerizable, non-gelled form after sterilization. Prior to describing this invention in further detail, the following terms will first be defined.
Definitions
As used herein, the following terms have the following meanings:
The term xe2x80x9ccyanoacrylate ester compositionsxe2x80x9d or xe2x80x9ccyanoacrylate compositionsxe2x80x9d refers to polymerizable formulations comprising polymerizable cyanoacrylate ester monomers and/or oligomers which, in their monomeric form, are preferably compounds represented by formula I as described above.
More preferably, in formula I, R is an alkyl group of from 2 to 10 carbon atoms including, by way of example, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, n-pentyl, iso-pentyl, n-hexyl, iso-hexyl, 2-ethylhexyl, n-heptyl, n-octyl, nonyl, and decyl. More preferably, R is butyl, pentyl or octyl and most preferably, R is n-butyl. Mixtures of such compounds can also be employed.
Polymerizable cyanoacrylate esters are known in the art and are described in, for example, U.S. Pat. Nos. 3,527,224; 3,591,676; 3,667,472; 3,995,641; 4,035,334; and 4,650,8261,2,7-10, the disclosures of each are incorporated herein by reference in their entirety.
A particularly preferred cyanoacrylate ester for use in the invention is n-butyl-2-cyanoacrylate.
The polymerizable cyanoacrylate ester compositions described herein rapidly polymerize in the presence of water vapor or tissue protein, and these prepolymers bond human skin tissue without causing histotoxicity or cytotoxicity.
Such polymerizable cyanoacrylate esters are sometimes referred to herein as prepolymers and compositions comprising such esters are sometimes referred to herein as prepolymer compositions.
The term xe2x80x9ca biocompatible polymerxe2x80x9d refers to polymers which, as iodine complexes (adducts), are compatible with in vivo applications of cyanoacrylate ester compositions onto mammalian skin including human skin. Representative polymers include polyvinylpyrrolidone, copolymers comprising polyvinylpyrrolidone which are optionally crosslinked, and the like. Suitable copolymers include copolymers of polyvinylpyrrolidone and vinyl acetate or other vinyl compounds which copolymers are optionally crosslinked with a polyisocyanate. The molecular weight of these polymers is not critical with number average molecular weights ranging from about 10,000 to about 1,000,000 and preferably from 30,000 to 300,000.
The term xe2x80x9ca complex of iodine molecules with a biocompatible polymerxe2x80x9d refers to an antimicrobial complex formed by the addition of iodine (I2) to the biocompatible polymer. Such complexes are well known in the art and the resulting complex typically comprises both available iodine and iodide anions. These complexes, on contact with mammalian skin, are antimicrobial apparently by providing for a source of antimicrobial iodine. In any event, such complexes are employed only as starting materials herein and, by themselves, do not form a part of this invention.
These complexes are sometimes referred to herein simply by the term xe2x80x9ciodine/polymer complexesxe2x80x9d. Such iodine/polymer complexes are distinguished from antibiotics which are naturally derived materials from either bacteria or fungi and whose mode of action is to interfere with bacterial processes resulting in bacterial death. Contrarily, the complexes used in this invention are indiscriminate in destroying any microbes including fungi, viruses and bacteria apparently by release of iodine into the microbes and, accordingly, are properly referred to as antimicrobial agents. Surprising, it has been found that iodine/polymer complexes are compatible in cyanoacrylate compositions. In fact, elemental (solid) iodine is incompatible with cyanoacrylate compositions because the addition of elemental iodine renders such compositions non-polymerizable on mammalian skin. Accordingly, complexation of the iodine with the biocompatible polymer is apparently essential for compatibility with the cyanoacrylate composition.
One preferred iodine/polymer complex for use in the compositions of this invention is either polyvinylpyrrolidone iodine complex which is described in, for example, the Tenth Edition of the Merck Index, Published by Merck and Co., Rahway, N.J., USA (1983). This complex is commercially available under the name xe2x80x9cpovidone-iodinexe2x80x9d from BASF, Mt. Olive, N.J., USA.
Other suitable antimicrobial agents include complexes of iodine molecules with poloxamers or copolymers of vinylpyrrolidone and vinyl acetate, copolymers of vinylpyrrolidone and vinyl acetate cross-linked with polyisocyanates, copolymers of vinylpyrrolidone and vinyl functionalities, polymers of pyrrolidone and the like.
The term xe2x80x9cbiocompatible plasticizerxe2x80x9d refers to any material which is soluble or dispersible in the cyanoacrylate composition, which increases the flexibility of the resulting polymer film coating on the skin surface, and which, in the amounts employed, is compatible with the skin as measured by the lack of moderate to severe skin irritation. Suitable plasticizers are well known in the art and include those disclosed in U.S. Pat. Nos. 2,784,12717 and 4,444,93318 the disclosures of both of which are incorporated herein by reference in their entirety. Specific plasticizers include, by way of example only, acetyl tri-n-butyl citrate (preferably xcx9c20 weight percent or less), acetyl trihexyl citrate (preferably xcx9c20 weight percent or less) butyl benzyl phthalate, dibutyl phthalate, dioctylphthalate, n-butyryl tri-n-hexyl citrate, diethylene glycol dibenzoate (preferably xcx9c20 weight percent or less) and the like. The particular biocompatible plasticizer employed is not critical and preferred plasticizers include dioctylphthalate and acetyl tri-n-butyl citrate.
The term xe2x80x9cpolymerization inhibitorxe2x80x9d refers to mixtures of conventional acid polymerization inhibitors and free radical inhibitors of cyanoacrylate esters including materials such as mixtures comprising a first inhibitor such as sulfur dioxide, glacial acetic acid, C2-C6 organic acids, and the like and a second inhibitor such as hydroquinone and hindered phenols. The polymerization inhibitor is typically employed in amounts effective to inhibit polymerization until application onto mammalian skin.
Because of its compatibility with topical skin applications, the acid polymerization inhibitor is preferably sulfur dioxide which is preferably employed at from about 50 to 1000 ppm, more preferably from about 50 to 500 ppm and even more preferably 100 to 300 ppm, based on the total weight of the composition. Other preferred acid polymerization inhibitors include glacial acetic acid and other organic acids (e.g., C2 to C6 organic acids). Preferred free radical inhibitors include hydroquinone which is preferably employed at from about 50 to 500 ppm. Other free radical inhibitors include hindered phenols such as 4-methoxyphenol, 2,6-di-tert-butylphenol, and the like.
The term xe2x80x9cantimicrobial agentxe2x80x9d refers to agents which destroy microbes (i.e., bacteria, fungi, viruses and microbial spores) thereby preventing their development and pathogenic action.
The term xe2x80x9csanitizing agentxe2x80x9d refers to any agent compatible with the packaging elements which, when contacted with these elements, sanitizes the package by reducing bioburden thereon. Preferably, bioburden is reduced to levels of less than about 10 colony forming units (CFU) on individual packaging elements and more preferably less than about 3 CFUs. Preferred sanitizing agents include, for example, heat, plasma and ethylene oxide. Other suitable sanitizing agents are well known in the art.
The term xe2x80x9cvisible lightxe2x80x9d refers to light having wavelengths of from about 200 to 780 nm, and preferably, 390 to 780 nm.
The term xe2x80x9ctransparent to visible light irradiationxe2x80x9d refers to packaging elements which permit sufficient visible light irradiation to pass through the packaging element to sterilize polymerizable cyanoacrylate compositions contained therein. Preferably, the packaging element will permit at least about 50% of the visible light irradiation incident to the surface of the packaging element to traverse through the element; more preferably, at least 70% and still more preferably at least 80%.
Methods
The methods of this invention involve visible light sterilization of polymerizable cyanoacrylate compositions. In a preferred embodiment, the cyanoacrylate composition is first packaged into a suitable visible light transparent container which is preferably air-tight and moisture resistant. Such containers include, for example, glass, polyalkylene based polymers such as polypropylene or polyethylene, and the like. One suitable packaging element is described by Askill, et al.15 Another suitable packaging element includes ampules made of polyolefins, fluorinated polyolefins and similar materials. Such materials possess low water vapor transmission and are inert to the cyanoacrylate ester.
In a preferred embodiment, the packaging element comprises high density polyethylene ampules having capacity of from about 0.3 to 10 mL of cyanoacrylate composition and a wall thickness of at least about 1 millimeter. In another preferred embodiment, polyolefin lined with a layer of silica is used as the packaging material because of its improved barrier properties and anticipated longer shelf life.
The packaging element is then filled to the desired level with a polymerizable cyanoacrylate ester composition using peristaltic or displacement pumps which are non-reactive with the cyanoacrylate composition. Filling of the packaging element employs any of several well known filling methods and the particular filling method is not critical to this invention and does not form part of the claimed invention. Once filled, the packaging elements are preferably sealed, again by conventional means. If necessary, the sealing means can include auxiliary sealing means. For example, an ampule comprising a screw cap sealing means can be further sealed by placement of a removable clear polymer coated film over the mouth of the ampule to which the screw cap overlays. Again, any conventional sealing means can be used as the sealing means does not form any part of this invention.
In one preferred embodiment, the ampule is open at one end prior to fill and subsequent to filling with the cyanoacrylate composition, the open terminus is compressed and heated sealed to effect closure.
In a particularly preferred embodiment, the ampule is subjected to a second packaging element such a polyfoil package or bag and then heated sealed to form a unitary packaging element for the ampule. Other secondary packaging elements which are water vapor resistant may employ form fill seal packaging equipment. The unitary packaging elements are then preferably boxed into groups or sets of elements which boxes are then subjected to visible light sterilization.
The packaging element, whether an individual element or individual elements combined by into larger packaging elements, is subjected to visible light sterilization. The visible light generator is any conventional generator of sufficient power and breadth of wavelength to effect sterilization. However, preferred generators are commercially available under the tradename PureBright(copyright) in-line sterilization systems from PurePulse Technologies, Inc. 4241 Ponderosa Ave, San Diego, Calif. 92123, USA.
The PureBright(copyright) in-line sterilization system employs visible light to sterilize clear liquids at an intensity approximately 90000 times greater than surface sunlight. Surprisingly, not withstanding the presence of UV radiation in the irradiation employed therein, it is contemplated that the methods of this invention will not result in significant polymerization of the cyanoacrylate composition.
If the amount of UV light penetration into the packaging element is of concern, the packaging element can incorporate a conventional UV absorber and/or the cyanoacrylate composition can be formulated with higher concentrations of stabilizers.
The dose of visible light irradiation employed is one sufficient to sterilize the packaging element as well as its contents. In a preferred embodiment, the visible light dosage is preferably from about 0.01 to 50 joules/square centimeter and more preferably from about 0.05 to about 5 joules/square centimeter with the specific dosage being selected relative to the density of material being subjected to visible light irradiation as well as the amount of bioburden estimated to be therein. Such factors are well within the skill of the art. Upon completion of the sterilization process, the sterilized product is ready for shipment to the ultimate user.
Visible light sterilization is preferably conducted at ambient atmospheric conditions such as a temperature of from about 15xc2x0 C. to about 30xc2x0 C. and the exposure time of the product to visible light irradiation is dependent on the fluence of the radiation employed and the dosage required which is well within the skill of the art. Preferably, exposure of the product to the visible light irradiation is less than 60 seconds. See, for instance, Clark, U.S. Pat. No. 5,925,885 which is incorporated herein by reference in its entirety.
In a particularly preferred embodiment, sterilization of the cyanoacrylate composition is facilitated by employing steps to reduce biocontamination of the packaging element and/or the cyanoacrylate composition prior to visible light irradiation sterilization. For example, the packaging element can be contacted with compatible sterilization or sanitization conditions prior to fill to reduce bioburden thereon. Since these sterilization or sanitization conditions are employed prior to incorporation of the cyanoacrylate composition, sterilization or sanitization conditions which are compatible with the packaging but would be otherwise incompatible with cyanoacrylate esters can be used including, for example, steam sterilization, heat sterilization, gas treatment, etc.
Likewise, the cyanoacrylate composition is preferably but optionally filtered with a small pore filter ( less than 1 micron pore size) prior to addition to the packaging element. Filtration through, for example, 0.22 micron filter effectively reduces microbial contamination in the cyanoacrylate composition.
Using such steps prior to irradiation with visible light effectively reduces the dosage necessary to sterilize the composition.
In a particular embodiment, a primary packaging element such as a polyethylene ampule constructed for closure by heat sealing is sanitized by contacting the ampule with ethylene oxide under conventional conditions which reduce the bioburden to approximately zero.
Next, a polymerizable cyanoacrylate composition is filtered through a small pore filter such as a 0.22 micron filter which comprises material inert to the cyanoacrylate esters such as Telfon(copyright) filters. The filtered material is added to the sanitized ampule which is then heat sealed. Preferably, filtration, addition and sealing are done in a Class 100,000 or better clean room. The cyanoacrylate composition employed in the methods described herein is preferably fully formulated and more preferably contains cyanoacrylate ester prepolymer and polymerization inhibitors and, in some embodiments, a plasticizer and/or an antimicrobial agent such as povidone iodine.
Alternatively, the packaging element can contain the antimicrobial agent as a separate component thereof such that a 2 component system is provided which, at time of use, can be combined to provide for a single composition. See, for example, Lee, et al., U.S. Pat. No. 6,090,397 issued on Jul. 18, 2000 which patent is incorporated herein by reference in its entirety.
The primary packaging elements in the form of clear ampules can then be loaded into a secondary packaging element, such as a clear plastic.
In a final step, the packaged product is then subjected to sterilization by exposure to visible light irradiation.
The methods of this invention are particularly useful insofar as visible light sterilization does not result in solidification or gelation of the cyanoacrylate ester composition. Rather, the sterilized composition is liquid and retains its polymerizable properties. If necessary, solidification and/or gelation of the polymerizable cyanoacrylate ester composition can be further retarded by the use of polymerization inhibitors.
Compositions
The cyanoacrylate compositions used in the methods of this invention are prepared by conventional techniques of mixing the appropriate components until homogenous.
The specific viscosity of these compositions depends, in part, on the intended application of the composition. For example, relatively low viscosities are often preferred where application is to be made to a large surface area (e.g., abdominal surfaces). This preference results from the fact that those forms are less viscous and, accordingly, will permit more facile large surface area application of a thin film. Contrarily, where application is to be made to a specific position on the skin (e.g., elbow surfaces, knee surfaces and the like), higher viscosity compositions, including those containing thixotropic materials, are preferred to prevent xe2x80x9crunningxe2x80x9d of the compositions to unintended locations.
Accordingly, these compositions have a viscosity of from about 2 to 50,000 centipoise at 20xc2x0 C. Preferably the less viscous compositions have a viscosity of from about 2 to 1,500 centipoise at 20xc2x0 C. More preferably, the cyanoacrylate ester employed in these compositions is almost entirely in monomeric form and the composition has a viscosity of from about 2 to about 100 centipoise at 20xc2x0 C.
A thickening agent is optionally employed to increase the viscosity of the composition, which thickening agent is any biocompatible material which increases the viscosity of the composition. Suitable thickening agents include, by way of example, polymethyl methacrylate (PMMA) or other preformed polymers soluble or dispersible in the composition, a suspending agent such as fumed silica and the like with PMMA being preferred. Fumed silica is particularly useful in producing a gel for topical application having a viscosity of from about 1500 to 50,000 centipoise at 20xc2x0 C. Suitable thickening agents for the compositions described herein also include a partial polymer of the alkyl cyanoacrylate as disclosed in U.S. Pat. Nos. 3,654,2393 and 4,038,34516 both of which are incorporated herein by reference in their entirety.
Thickening agents are deemed to be biocompatible if they are soluble or dispersible in the composition and are compatible with the skin as measured by the lack of moderate to severe skin irritation.
Alternatively, the sterilization conditions can be selected such that the cyanoacrylate ester undergoes partial polymerization to reactive oligomers having a higher viscosity.
The cyanoacrylate compositions preferably include a biocompatible plasticizer and such plasticizers are preferably included in the composition from about 10 to 30 weight percent and more preferably from about 18 to 25 weight percent based on the total weight of the composition.
Additionally, the cyanoacrylate compositions described herein preferably include a mixture of polymerization inhibitors in an effective amount to inhibit premature polymerization of the composition during storage. Preferred mixtures of polymerization inhibitors are described above.
The polymerizable cyanoacrylate ester compositions may additionally contain one or more optional additives such as colorants, perfumes, rubber modifiers, modifying agents, etc. In practice, each of these optional additives should be both miscible and compatible with the cyanoacrylate composition and the resulting polymer. Compatible additives are those that do not prevent the use of the cyanoacrylates in the manner described herein.
In general, colorants are added so that the polymer layer formed on the skin will contain a discrete and discernable color. Perfumes are added to provide a pleasant smell to the formulation. Rubber modifiers are added to further enhance the flexibility of the resulting polymer layer. The amount of each of these optional additives employed in the composition is an amount necessary to achieve the desired effect.
Preferred cyanoacrylate compositions useful in the practice of this invention are also disclosed by Greff, et al.14 which is incorporated herein by reference in its entirety.
In a particularly preferred embodiment, the cyanoacrylate composition further comprises an antimicrobially effective amount of a compatible antimicrobial agent. Such compositions preferably comprise from about 1 to about 30 and more preferably 3 to 20 weight percent of the compatible antimicrobial agent either as a solution or as a suspension based on the total weight of the composition. Compatible antimicrobial agents are those which are either soluble or suspendable in the cyanoacrylate composition, which do not cause premature polymerization of the cyanoacrylate composition, which do not prevent polymerization of the cyanoacrylate composition when applied to mammalian skin, and which are compatible with the intended use including biocompatibility with the patient""s skin.
In a particularly preferred embodiment, the compatible antimicrobial agent comprises a complex of iodine molecules with a biocompatible polymer. Such complexes are well known in the art and the resulting complex typically comprises both available iodine and iodide anions. These complexes, on contact with mammalian skin, provide for a source of antimicrobial iodine. In any event, such complexes are employed only as starting materials herein and, by themselves, do not form a part of this invention. Suitable biocompatible polymers include, by way of example only, polyvinylpyrrolidone polymer which, when complexed with iodine, is also referred to under the common name of povidone-iodine available from BASF, Mt. Olive, N.J., USA. When povidone-iodine is employed in the cyanoacrylate composition, the composition preferably comprises from about 1 to about 30 weight percent and more preferably from about 3 to 20 weight percent of povidone-iodine based on the total weight of the composition.
Cyanoacrylate compositions comprising, for example, povidone-iodine are described by Greff, et al.19, U.S. Pat. No. 5,684,042 which patent is incorporated herein by reference in its entirety.
Other suitable antimicrobial agents include complexes of iodine molecules with poloxamers or copolymers of vinylpyrrolidone and vinyl acetate, copolymers of vinylpyrrolidone and vinyl acetate cross-linked with polyisocyanates, copolymers of vinylpyrrolidone and vinyl functionalities, polymers of pyrrolidone and the like.
The use of a compatible antimicrobial agent in the composition permits the agent to be released from the polymeric film formed on mammalian skin thereby inhibiting microbial growth under this film. Additionally, since the film is maintained on mammalian skin for 1-4 days after formation, the release of antimicrobial agent further provides long term anti-infection benefits.
Utility
The methods of this invention are useful in providing sterilized cyanoacrylate compositions which can then be used for topical application to mammalian skin with reduced risk of introducing microbes onto the skin and, accordingly, reduced risk of infection. This is particularly important where topical application is onto skin areas which are already broken (e.g., small topical skin wounds or closing the surgical incision site) or which will become broken (e.g., application to form a surgical incise drape which will then be broken by the incision initiating the surgery).

Methods for sterilizing cyanoacrylate compositions


A hot water tank construction, parts therefor and methods of making the same are provided, the hot water tank construction comprising a hot water tank having a wall provided with an opening therethrough and a spud carried by the wall and having an opening therethrough that is disposed in aligned relation with the opening in the wall, and a fuel control valve unit having a shank provided with a portion thereof disposed in the opening of the spud and being interconnected to the opening of the spud so as to be carried by the wall, the opening of the spud having axial securing structure therein, the portion of the shank having axial securing structure thereon, the portion of the shank having been axially pushed into the opening of the spud until the portion is in a predetermined position thereof whereby the axial securing structures cooperate together to interconnect the fuel control valve unit to the spud.

1. Field of the Invention
This invention relates to a new hot water tank construction and to new parts for such a hot water tank construction as well as to new methods of making such a hot water tank construction and such new parts therefor.
2. Prior Art Statement
It is known to provide a hot water tank construction comprising a hot water tank having a wall means provided with an opening therethrough and a spud carried by the wall means and having an opening means therethrough that is disposed in aligned relation with the opening, and a fuel control valve unit having a shank provided with a portion thereof disposed in the opening means of the spud and being interconnected to the opening means so as to be carried by the wall means. The portion of the shank is externally threaded so that the portion can be threaded into the internally threaded opening means of the spud by rotating the control valve unit.

Hot water tank construction, parts therefor and methods of making the same


An amplifier selector for use with a MRI machine having stacked amplifiers. The selector includes a switch assembly carried by each amplifier and controlled by a central controller. Each switch assembly includes a motor for rotating a plurality of switch plates to various predetermined stations. The stations connect the input and output terminals of the slave amplifier to either the X, Y or Z axis of the MRI machine. A fourth station is included to define an off line condition for the amplifier.

This invention relates to gradient amplifiers and will have specific reference to a switch device for reconfiguring a plurality of stacked gradient amplifiers for use with a nuclear magnetic resonance imaging machine.
Nuclear magnetic resonance imaging (MRI) has revolutionized the medical field in the diagnosis and treatment of patients and has gained wide acceptance since its inception in the early 1970's. As is commonly known, MRI machines use large coils to set up a magnetic field into which the patient is inserted. To generate these large magnetic fields a plurality of power amplifiers associated with each of the coils is required. Typically two or three power amplifiers are associated with each of the three MRI coils or axes.
One of the most significant advances in MRI is the development of fast-scan technology. Fast-scan technology is used to view movable parts of the body, such as the patient's heart or joints. One drawback to using fast scan technology is that the voltage waveforms needed on the fast scan axis have unusually fast rise and fall times which require increased voltage to the coil. Therefore, the hospital or laboratories using fast scan technology have previously had the option of either buying additional amplifiers to be placed on all three axes or to use manual means to configure the system such that enough amplifiers (sufficient voltage) could be placed on the fast scan axis. A problem associated with the option of providing a sufficient voltage on all axes is the cost of additional amplifiers to the hospital. Similarly, there is machine down time when one must manually reconfigure the gradient amplifier.
A further problem experienced in MRI machines in general is associated with common fatigue and breakdown of the amplifiers. A malfunctioning amplifier causes the MRI machine to become inoperative. While it is possible for the hospital to maintain a standby amplifier at considerable cost, the replacement time for a technician to be called to the site and replace the down amplifier will be an additional expense for the hospital.

Amplifier selector for magnetic resonance imaging machine


A mobile computer includes a liquid display unit pivoted to a mainframe unit consisted of a keyboard, a floppy diskdrive, a hard diskdrive, a battery power supply and a mother board circuit assembly, wherein the liquid crystal display unit is consisted of a display board revolvably fastened inside a rectangular frame by stub tubes and has a penbase input circuit inserted through the stub tubes for connecting a penbase so that data entry can be made through a penbase as the display board is turned upside down on the rectangular frame.

The present invention relates to a mobile computer which allows entry of data to be alternatively made through a keyboard or penbase.
A wide variety of portable computers including notebook and palm-top computers, are widely accepted by people in all fields and countries for the advantage of mobility. A mobile computer may be attached with a keyboard or penbase for data entry. It is very convenient to use a penbase for data entry. However, every stroke must be correctly written when a penbase is used. A keyboard requires much installation space, but it is convenient for mass data input.

Mobile computer with pen base/keyboard input modes


The present invention provides a method of inhibiting connective tissue degradation that comprises administering to a patient having a condition in which connective tissue is degraded a therapeutically effective amount of a compound having the formula ##STR1##. where R.sub.1, R.sub.2, R.sub.3, and R.sub.4 are independently hydrogen, hydroxy, halo, amino, nitro, C.sub.1 -C.sub.6 alkyl, C.sub.3 -C.sub.6 cycloalkyl, C.sub.1 -C.sub.6 alkoxy, CF.sub.3, CN, S(O).sub.n --, ##STR2## PA1 R.sub.6 and R.sub.7 are independently hydrogen, C.sub.1 -C.sub.6 alkyl, or acyl; PA1 n is 0 to 2; PA1 R.sub.8 is hydrogen or C.sub.1 -C.sub.6 alkyl; ##STR3## PA1 W is S or O; PA1 Z is C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkoxy, or NR.sub.9 R.sub.10 ; PA1 R.sub.9 and R.sub.10 are independently hydrogen or C.sub.1 -C.sub.6 alkyl; and PA1 R.sub.5 is ##STR4## PA1 where Y is hydroxy, thiol, amino, or NHCN; PA1 X is sulfur or oxygen; and Q is sulfur, oxygen, NH, or NCN, and the pharmaceutically acceptable salts and prodrugs thereof. Also provided is a method of inhibiting the production of matrix metalloproteinases comprising administering to a patient having a condition associated with matrix metalloproteinase-mediated tissue degradation a therapeutically effective amount of a compound having the formula ##STR5##. where R.sub.1, R.sub.2, R.sub.3, and R.sub.4 are independently hydrogen, hydroxy, halo, amino, nitro, C.sub.1 -C.sub.6 alkyl, C.sub.3 -C.sub.6 cycloalkyl, C.sub.1 -C.sub.6 alkoxy, CF.sub.3, CN, S(O).sub.n --, ##STR6## PA2 R.sub.6 and R.sub.7 are independently hydrogen, C.sub.1 -C.sub.6 alkyl or acyl; PA2 n is 0 to 2; PA2 R.sub.8 is hydrogen or C.sub.1 -C.sub.6 alkyl; ##STR7## PA2 W is S or O; PA2 Z is C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkoxy, or NR.sub.9 R.sub.10 ; PA2 R.sub.9 and R.sub.10 are independently hydrogen or C.sub.1 -C.sub.6 alkyl; and PA2 R.sub.5 is ##STR8## PA2 where Y is hydroxy, thiol, amino, or NHCN; PA2 X is sulfur or oxygen; and Q is sulfur, oxygen, NH, or NCN, and the pharmaceutically acceptable salts and prodrugs thereof.

In certain conditions, connective tissues in a patient are detrimentally degraded. For example, cartilage can be degraded as a result of a disease, or injury from a mechanical trauma, such as a sports accident; the bones or intervertebral disks of a patient can be degraded due to various environmental conditions or diseases; dermis of the skin can be degraded in the elderly causing chronic ulcers; and degradation of the connective tissue of blood vessels can lead to aneurysm formation or atherosclerosis. The term "connective tissue" means the structural framework of organs containing supporting matrix molecules such as collagens, elastins, and proteoglycans (glycosaminogylcans).
In conditions in which connective tissue degradation occurs, matrix metalloproteinases are known to play an important role in the degradation of the tissues. A good review of the matrix metalloproteinases and their role in tissue degradation can be found in the article "Matrix Metalloproteinases and Their Inhibitors In Connective Tissue Remodelling" by J. Frederick Woessner, Jr., The FASEB Journal, 1991;5:2145-2154.
Presently, there is no way of inhibiting the tissue degradation that results from such conditions, and physicians have, instead, prescribed compounds that act to mask the symptoms, i.e., ameliorate the pain associated with such conditions, but these compounds have not inhibited the tissue degradation. That is, destruction of the tissues continues unabated despite symptomatic relief. Eventually, the tissues are destroyed by the disease process and dysfunction occurs.
Thus, it would be beneficial to have a method to inhibit connective tissue degradation in a patient.

Method of inhibiting connective tissue degradation


The present invention relates to a protective coating composition for electrical or electronic circuits containing a curable polyvinyl acetal polymer and a non-ionic corrosion inhibitor such as an azole. The invention also relates to a method of protectively coating electrical or electronic circuits.

In recent years there has been an ever increasing application of electronics circuits in equipment used in aggressive environments and high damage risk areas. This includes for example a wide variety of electronic navigation and communication equipment on ships and small boats, monitoring and analysis equipment in mines and factories, telecommunication equipment in outdoor locations, small computers in field and un-airconditioned environments. A frequent cause of failure of this equipment is related to water, water based solutions, salts and reactive gases coming into contact with the components of electronic circuits. When this occurs the damage can be either immediate (as in the case of salt solutions producing short circuits between components) or gradual (as in the case of corrosion attack on the metallic components).
Thus, it is desirable to provide some form of protection. Such protection may typically be in the form of a coating. The coating should preferably form a thin film on the components and thus minimize reductions in heat transfer from the components to the air. If heat transfer is not adequate the components may become overheated and fail. The coating should preferably be transparent so all components may be readily identified.
It is desirable that the coating dry rapidly so as to minimize any delay between coating and returning a circuit to service in field application, and to minimize production time in factory application.
The coating should preferably also dry to a hard, glossy film. A hard glossy film is desirable since it reduces the tendency of foreign particles, for example, dust, dirt and wind blown salt to adhere subsequently to the surface where they could cause damage through short circuiting or assisting corrosion.
The coating should preferably be readily removable so that soldering of the circuits is not prevented or impaired. When cured, the coating should preferably not have any tendency to spread over uncoated areas where the formation of an insulating layer could interfere with the operation of components.

Protective coating for an electrical or electronic circuit


A potato plant which has a genome containing, as a result of genetic engineering, at least one gene construct containing a potato granule-bound starch synthase (PGBSS) cDNA or genomic DNA sequence in reverse or functional orientation in an expression cassette which is functional in potato plants, the gene construct giving rise to tubers containing essentially amylose-free starch. In one embodiment, the gene construct contains a PGBSS cDNA sequence in reverse orientation which results in the production of PGBSS antisense RNA.

The invention is in the field of genetic engineering by recombinant DNA technology, more particularly the genetic engineering of potato plants in order to change the starch composition in the tubers towards essentially amylose-free starch.
Starch is the major storage carbohydrate in potato and consists of two components, a linear (1xe2x86x924)xcex1-D-glucan polymer and a branched (1xe2x86x924) (1xe2x86x926)xcex1-D-glucan called amylose and amylopectin, respectively. Amylose has a helical conformation with a molecular weight of 104-105. Amylopectin consists of short chains of xcex1-D-glucopyranose units primarily linked by (1xe2x86x924)xcex1 bonds with (1xe2x86x926)xcex1 branches and with a molecular weight up to 107. In plants starch is found in two types of plastids: chloroplasts and amyloplasts. In both types of organelles the starch occurs as granules. In chloroplasts so-called transitory starch is accumulated for only a short period of time, whereas starch in amyloplasts is accumulated for long term storage and hence is named reserve starch. Generally, amylose makes up 11%-37% of the total reserve starch and variation in the amylose content is not only found among different plant species, but also among different cultivars of the same species. In potato the amylose content in the tuber varies from 18% to 23%. Furthermore, in a number of plant species mutants are known with a starch composition which deviate significantly from the above mentioned percentages.
Transitory and reserve starch are generally considered to be synthesized by the same enzymes. Starch metabolism in leaves follows a diurnal rhythm: synthesis and accumulation occur during the light period while hydrolysis occurs during the night. In storage tissue, starch synthesis occurs during a specific phase of tissue development; the synthesis being the predominant function of amyloplasts. The amount of amylose found in storage tissue of potato is about twice as high as that in leaves.
Sucrose is considered to be the major substrate for starch biosynthesis which involves the following steps: initiation, elongation, branching and granule formation. In the pathway of conversion of sucrose into amylose and amylopectin at least 13 enzymes play a role. Three groups of enzymes are directly involved in the formation of starch. These enzymes are phosphorylase, starch synthases and branching enzymes. Phosphorylase is active in starch breakdown, branching enzyme converts amylose into amylopectin by the breakage of (1xe2x86x924)xcex1-bonds and the synthesis of (1xe2x86x926)xcex1-bonds. Starch synthases are responsible for the synthesis of starch by the addition of ADP (UDP) glucose subunits to the non-reducing end of an (1xe2x86x924)xcex1-D-glucan polymer. Starch synthase has been identified in two forms: one form is soluble while the other is tightly associated with starch granules. The soluble enzyme uses only ADP-glucose as the D-glucosyl donor, whereas the granule bound starch synthase (GBSS) utilizes ADP-glucose and UDP-glucose. Solubilization of the GBSS protein from starch granules of various plants has been reported. Although in maize there are thought to be at least two forms of GBSS, potato seems to have only one form. The presence and activities of the different starch synthases are important to starch biosynthesis not only because they have an effect on the amylose/amylopectin ratio in starch, but also because they can have a large impact on total starch content. In general, it appears that complete suppression of the enzymes producing amylose can be achieved with almost no change in the total amount of starch laid down, whereas suppression of the enzyme system producing amylopectin leads to a marked decrease of the amount of total starch.
Starch as such or in modified form is widely used in the food, paper and textile industries. With the depletion of natural oil resources starch could also become a substitute for oil as a raw material for the chemical industry. Therefore, it could become of major interest to produce starch which meets special requirements for certain applications. Although special forms of starch are already available from mutants of maize and rice and starches from other sources might have certain advantages, genetical engineering could be an option in order to obtain tailor-made starches in plants in which (recessive) mutants are not easily obtained. Selection of mutants is especially difficult in vegetatively propagated crops which are mainly crosspollinators and/or polyploids, such as the potato.
Although recently in a laborious isolation procedure a mutant of potato (amf) was isolated which, in analogy to the wx mutants in maize, lacks GBSS protein, GBSS activity and amylose (Hovenkamp-Hermelink et al. 1987), the breeding of such a mutant into a cultivar will take another number of years. One cause for the long duration of the procedure is the fact that a haploid clone had to be used for the isolation of the recessive mutant. To circumvent problems of isolating recessively inherited mutants in a polyploid crop like potato and to speed up the introduction of such a mutant character in potato varieties, the antisense approach would be a very important alternative, because an antisense gene would act as a dominant suppressor gene. The great advantage is that eventually it will become possible to mimick such a mutant phenotype directly in a tetraploid variety. With the availability of GBSS sequences, both from maize (Shure et al 1983) and potato (Hergersberg 1988; Visser et al 1989d) and an efficient transformation system for potato (Visser et al 1989a, 1989b) this approach could be tested.
It has been shown that antisense RNA transcripts can be used to mimic mutations in pro- and eukaryotes (for review see van der Krol et al. 1989). Antisense RNA was originally found as a naturally occurring mechanism used to control gene expression in bacteria (Tomizawa et al. 1981; Mizuno et al. 1984). Izant and Weintraub (1984, 1985) proposed that antisense RNA could be used to inhibit the expression of eukaryotic genes. By inhibiting the expression of specific target RNAS, this approach has led to the generation of mutant phenotypes in a number of different eukaryotic systems. In plants the use of antisense RNA proved to be successful in effectively inhibiting the activity of nopaline synthase (Rothstein et al. 1987; Sandler et al. 1988), chloramphenicol acetyltransferase (Ecker and Davis 1986; Delauney et al. 1988), chalcone synthase (van der Krol et al. 1988), polygalacturonase (Smith et al. 1988; Sheehy et al. 1988), phosphinotricin acetyl transferase (Cornelissen and Van de Wiele 1989) and xcex2-glucuronidase (Robert et al. 1989).
Visser (1989) tested whether the antisense approach could be used to inhibit the expression of the gene for granule-bound starch synthase in potato using heterologous antisense constructs, i.e. an antisense gene constructed from a maize genomic GBSS gene.
The antisense gene was fused between the 35S cauliflower mosaic virus promoter and the nopaline synthase terminator in the binary vector pROK-1, which also carries a plant selectable kanamycin resistance gene. Since it was known from the amf-mutant that the mutation is expressed in all tissues in which starch is formed, including columella cells of the root cap, it was expected that also antisense effects would be visible in roots. The presence or absence of amylose could be easily detected because amylose forms a blue staining complex with the iodine present in Lugol""s solution (Ixe2x80x94KI). Starch without amylose, i.e. only containing amylopectin, forms a reddish-brown staining complex with iodine. In order to efficiently test the introduced antisense gene in potato for a biological effect a transformation system was developed in which the binary antisense vector was incorporated into Agrobacterium rhizogenes. The binary vector was present next to the wildtype Ri-plasmid of A. rhizogenes which is responsible for the formation of so-called hairy roots on plant explants. Agrobacterium rhizogenes was used instead of Agrobacterium tumefaciens because it is possible to screen for an effect of the introduced constructs already after 10 days by staining hairy roots with Lugol""s solution and because plants can be easily regenerated from hairy roots. In this way heterologous (maize) binary antisense GBSS plasmids were transferred by A. rhizogenes to stem segments from potato.
Both in untransformed or otherwise transformed wildtype roottips never anything else than blue staining roottips were present. Hairy roots obtained after transformation with A. rhizogenes carrying heterologous binary antisense GBSS plasmids were analyzed for the presence or absence of amylose in their starch by staining the roottips with Lugol""s solution. The majority of the roots stained blue as wildtype untransformed roots did. However, some roots (1-15% of the stained roots) had a color pattern different from that of wildtype roots in that the central cells of the root cap were blue and the cells towards the outside of the rootcap were red. These intermediate colouring roots were indications that the inserted antisense genes had some effect on the amylose content. Root clones were established and subcultured and roottips were investigated every fortnight during six weeks of culture. The results of these experiments showed that instability of color patterns occurred at a rather high frequency. The instability of the effect in columella cells was the reason to regenerate plants from kanamycin resistant hairy roots irrespective of their color.
On plants, regenerated from kanamycin resistant hairy roots, microtubers as well as soil grown tubers were induced. Analysis of these tubers showed that none of them had red or intermediate staining starch. All tubers showed blue staining (=amylose containing) starch. Starch isolated from these tubers was analyzed for the presence of GBSS protein and GBSS activity and for the presence of amylose. In all tubers tested GBSS protein was, seemingly unaltered, present. However, GBSS activity in particular and to a much lesser degree amylose content were affected in starch preparations from a number of transformed plants. As shown in FIG. 2A, the untransformed wildtype (PD007) and a pBI121 transformed wildtype (Ri-007) had similar GBSS activities, while the amf-mutant had no detectable GBSS activity. GBSS activity was inhibited significantly in the antisense GBSS transformants down to only 10% of that found in wildtype plants. Total inhibition of GBSS activity was not obtained in any of the transformants analyzed. The amylose content measurements gave a different picture. Although in almost all cases there was a somewhat lower amylose content, the difference was significant in only two cases (R-196 and R-227, FIG. 2B). The maximum reduction of the amylose content was found in transformant R-196, which also had the lowest GBSS-activity; a reduction down to 78% of the wildtype amylose content. Molecular analyses of the antisense transformants revealed that the number of integrated antisense copies was 1 to 4, but only those plants which contained three or more copies of the antisense GBSS construct showed a pronounced effect on GBSS activity. It is evident from these observations that the effect of a lower GBSS activity on the amylose/amylopectin ratio is not straightforward.
The results described resemble very closely the situation obtained in tomato when using antisense poly-galacturonase genes. A reduction of 90% of the polygalacturonase activity does not have a great effect on the lycopene content (Sheehy et al. 1988, Smith et al. 1988).
The above results were not too encouraging, but it was nevertheless decided to expand the investigations to homologous constructs derived from a full-length potato GBSS cDNA.
Surprisingly, it was found that it is possible to inhibit the expression of granule-bound starch synthase (GBSS) in potato, and thus affect the amylose content of potato tuber starch, by stably introducing homologous antisense constructs. The results described show that it is possible using the antisense approach to interfere with enzymes in biosynthetic pathways such as starch biosynthesis. In using this technique loss of function mutations, such as the amf mutation, which are principally inherited recessively can be mimicked, because antisense genes act as dominant (hemizygous) genes suppressing translation of mRNA.
Surprisingly, it was subsequently found that the effect of essentially amylose-free tuber starch could also be obtained by stably introducing homologous sense constructs, e.g. based on potato GBSS genomic DNA. A phenomenon known as co-suppression appears to occur; it is not yet possible to give an explanation of it.
The invention provides a potato plant which has a genome containing, as a result of genetic engineering, at least one gene construct containing a potato granule-bound starch synthase (PGBSS) cDNA or genomic DNA sequence in reverse or functional orientation in an expression cassette which is functional in potato plants, said gene construct giving rise to tubers containing essentially amylose-free starch.
In one preferred embodiment, said gene construct contains a PGBSS cDNA sequence in reverse orientation which results in the production of PGBSS antisense RNA.
In another preferred embodiment, said gene construct contains a PGBSS genomic DNA sequence in functional orientation which results in co-suppression of PGBSS enzyme activity.
The invention further provides cells, parts and tubers of said potato plant, and essentially amylose-free starch from it.
The invention will be illustrated by means of examples which are given for illustrative purposes only and may not be construed as limiting the scope of the invention. For example, the transformation system used in example 1 (Agrobacterium rhizogenes) may be replaced by any suitable alternative, such as the Agrobacterium tumefaciens transformation system (see ex. 2) or the direct gene transfer technique (DGT). Such alternatives are well known to the person skilled in the art. A survey of transformation systems suitable for potato is given in chapter I of Visser (1989).
Similar remarks apply to the choice of the transformation vector (if any), the elements of the expression cassette, the selection markers, etc. For example, the PGBSS promoter may be used to regulate the transcription of the sense or anti-sense PGBSS DNA, instead of the CaMV promoter used in example 1. The sense or anti-sense PGBSS cDNA or genomic DNA sequence does not have to cover the complete coding sequence but should cover a sufficient part of it to be effective for obtaining tubers containing essentially amylose-free starch. At present, the use of anti-sense PGBSS cDNA is preferred above using anti-sense PGBSS genomic DNA. The gene construct used may contain the PGBSS DNA (preferably genomic DNA) in its functional orientation and yet result in essentially amylose-free tuber starch.

Potato plant producing essentially amylose-free starch

Cooperatieve Verkoop-en Productievereniging van Aardappelmeel en Derivaten AVEBE B.A.


A computer system configured to evaluate a portfolio comprising instruments, comprising a computer memory configured to store, for each instrument, an instrument value for each portfolio scenario in an n-dimensional matrix, a first constraint and a second constraint; and a computer processor configured to transpose the n-dimensional matrix, to determine a first solution by maximizing the product of transpose of the n-dimensional matrix and the first constraint, determine whether the first solution is within an accepted range of an acceptable risk, if the expected first solution is not within an accepted range of an acceptable risk, process the second constraint with the first solution to obtain a second solution, and determine whether the second solution is within the accepted range of the acceptable risk.

A technical problem facing those interested in evaluating large portfolios of financial instruments is that the evaluation problems are very complex and the current technical solutions for evaluating them are not efficient to permit a timely analysis. Evaluation of the portfolios are defined by many permutations, constraints, and variables, such that when a significant number of financial instruments need to be evaluated, the complexity of the problem is too large to solve in a timely and efficient matter. Current technical solutions are inefficient because the problems are not efficiently solved to permit evaluation of the financial instruments in a timely manner to react to different potential scenarios that may arise.
One specific application where this problem arises is in the evaluation of insurance portfolios. Insurance portfolios generally comprise a significant number of financial instruments, such as insurance policies. Each financial instrument within the portfolio has an expected value for a given scenario. A scenario is, for example, a different event, such as a hurricane, earthquake, flood, wind storm, hail storm, ice storm, snow event, fire, having a certain severity. Because the events vary in severity, there are many different scenarios for each type of event. It is helpful to evaluate a portfolio of insurance financial instruments under the many different events at different severity levels to determine the value of the financial instrument under each event and each severity. It is further helpful to determine how to maximize or minimize values associated with the portfolio. For example, it is desirable to evaluate how to maximize the profits of the financial instruments for a given risk, or how to determine the risk for a given desired profit. Generally, the current technical solutions for doing so are not efficient and timely to permit timely decisions based on evaluating this data. The inventions disclosed herein address that problem by providing new technical solutions that permit the timely and efficient evaluation of the portfolio such that it can be optimized. The timely evaluation permits consideration of which instruments to sell, buy, adjust pricing, or adjust policy terms.

Portfolio optimization and evaluation tool


A pattern-forming method includes providing a first ion beam at a first incidence angle and a second ion beam at a second incidence angle to a surface of an etch target layer formed on a substrate. Patterns are formed by patterning the etch target layer using the first and second ion beams. The first ion beam and the second ion beam are substantially symmetrical to each other with respect to a normal line that is perpendicular to a top surface of the substrate. Each of the first and second incidence angles is greater than 0 degrees and smaller than an angle obtained by subtracting a predetermined angle from 90 degrees.

Example embodiments of the inventive concepts relate to a method of forming a pattern using ion beams of bilateral symmetry, a method of forming a magnetic memory device using the same, and an ion beam apparatus generating ion beams of bilateral symmetry.
Magnetic memory devices are being developed as semiconductor memory devices satisfying the industry demands for higher speed and lower power consumption memory devices. Magnetic memory devices are next-generation semiconductor memory devices because of their high-speed performance and non-volatile characteristics.
Generally, magnetic memory devices may include a magnetic tunnel junction (MTJ) pattern. The MTJ pattern may include two magnetic layers and an insulating layer disposed between the two magnetic layers. A resistance value of the MTJ pattern may be changed according to magnetization directions of the two magnetic layers. For example, the MTJ pattern may have a relatively high resistance value if the magnetization directions of the two magnetic layers are anti-parallel to each other. The MTJ pattern may have a relatively low resistance value if the magnetization directions of the two magnetic layers are parallel to each other. Data values may be represented in the MTJ pattern using a difference between the resistance values.
The electronic industry is increasingly demanding more highly integrated and lower power consuming magnetic memory devices. Accordingly, research is being conducted into various ways for satisfying these demands.

Ion beam apparatus generating ion beams of bilateral symmetry


Bipolar crossed-field device 10 has outer electrode 12 and inner electrode 18 which define interelectrode space 16. Magnetic field coils 46, 48 operate together to form a magnetic field in the interelectrode space 16 shaped to trap electrons for cascading ionization and plasma formation when viewed from either electrode.

This invention is directed to a bipolar crossed-field switch device wherein potential may be applied in either direction for on-switching, or current can flow in either direction for off-switching of the switch device.
R. J. Harvey, U.S. Pat. No. 4,071,801 describes a crossed-field switch device having a single interelectrode space or gap, with control of the magnetic field causing off-switching. That patent describes an improvement over the general background. H. E. Gallagher and Wolfgang Knauer are inventors of U.S. Pat. No. 3,906,270 and U.S. Pat. No. 3,963,960. Both of these are directed to bipolar structures. Gallagher and Knauer, U.S. Pat. No. 3,906,270 describes a single gap crossed-field switch device wherein the magnetic field is shaped to provide for substantially uniform conduction in either polarity. That patent also identifies the early prior art in crossed magnetic and electric field devices, such as those in the Penning U.S. Pat. No. 2,182,736 & Boucher U.S. Pat. Nos. 3,215,893 and 3,215,939. On the other hand, Gallagher and Knauer, U.S. Pat. No. 3,963,960 is directed to a two interelectrode gap device, one having three electrodes, and it identifies in its background the G. A. G. Hofmann et al., U.S. Pat. No. 3,641,384 patent which has a three electrode structure with two interelectrode spaces. The R. J. Harvey and the two Gallagher and Knauer U.S. patents identified above are incorporated herein in their entirety, including their background references, by this reference.
These patents point up the difficulty of providing a structure wherein the physical process produces the plasma with sufficient uniformity in each direction that bipolar on-switching, conduction and off-switching can be achieved. Such is necessary where the crossed-field switch device is applied in an alternating current circuit, particularly a high speed circuit which can be actuated in a fraction of a cycle. Such structures are necessary for increasing the impedence in faulted alternating current high voltage lines.

Bipolar crossed-field device including electromagnetic coils of the same polarity


In a receiving apparatus for detecting the presence or absence of periodically keyed random modulated signals, there are provided a pair of separate and distinct detection channels. One channel produces a real signal having clock line components and the other channel produces a decorrelated imaginary signal having no clock line components. The real and imaginary signals having carrier wave interference signals are processed in a Fourier transform device and a post processor to cancel out the carrier wave interference signals and to provide only a clock signal output when periodically keyed random modulated signals are being received.

1. Related Applications
This invention is an improvement of application Ser. No. 408,542 filed Aug. 16, 1982 by Samuel C. Kingston for a "Dual Channel Clock Recovery Circuit".
2. Field of the Invention
This invention relates to the detection of covert communication signals. More particularly, this invention relates to an improved novel circuit for detecting the presence of signals which typically are received at very low signal to interference and noise ratios.
3. Description of the Prior Art
The general class of signals to which the present invention is directed are commonly referred to as periodically keyed random modulated signals. For example, communications intelligence is often transmitted in coded form. One former way of denying data access to the enemy is to transmit the data stream in direct sequence spread spectrum format. It is extremely difficult to detect data signals embedded or encoded in such spread spectrum format because the signal-to-noise ratio is so low as to make detection difficult.
Before it is possible to attempt to decode direct sequence spread spectrum coded data signals, it is necessary to determine that such coded signals are actually being transmitted. This invention is directed to the problem of detecting that such coded signals are being transmitted and is not directed to the problem of decoding such signals.
It has been suggested that radiometers or power signal detection devices may be employed to determine if periodically keyed random modulated signals are being transmitted. When such signals are received at a receiver, it is often impossible to distinguish them from the received noise, thermal background noise, other transmitted signals and interferring emission signals. It is possible that the power level of the signals which are to be detected, do not exceed the background and interference signals mentioned above thus, it is often impossible to employ radiometers and power detection devices to detect the presence of low power periodically keyed random modulated signals.
When a radiometer is employed to detect the presence of a signal, then the threshold of a detector must be set very close to the signal levels. Changes in either the interference levels or the threshold levels will affect the sensitivity of the receiver which results in false alarms or reduced sensitivity. For example, if the threshold of a radiometer is set to detect the desired signal at minus 20db signal-to-noise ratio, then a one percent increase in interference level will cause a false alarm.
It has been suggested that since periodically keyed random modulated signals by definition change symbols at a fixed rate, it may be possible to detect a periodic repetition as a clock signal even though the data signal is not discernable.
In the above-mentioned application Ser. No. 408,542, the received periodically keyed random modulated signals were split into two separate and distinct channels, each comprising a narrow band pass filter. One of the narrow band pass filters in one of the channels was tunned to a frequency higher than the expected center frequency of the periodically keyed random modulated signals and the other narrow band pass filter was tunned to a frequency lower than the expected center intermediate frequency. The distance between centers of the narrow band pass filter frequencies was designed to be approximately the clock frequency to be detected, thus, both channels contain spectral signals indicative of the clock signal to be detected. The outputs from the narrow band pass filters were connected to a mixer to provide an output signal therefrom representative of a clock having a frequency equal to the periodically keyed random modulated signal. The output from the mixer was detected and/or analyzed for the presence of a clock signal by comparing the mixer output with a reference frequency or a reference voltage. While this apparatus and structure is extremely effective in detecting the presence or absence of periodically keyed random modulated signals, the signals being analyzed and/or compared include interference lines representative of continuous wave (C.W.) interference signals.
It would be extremely desirable to eliminate the C.W. interference signals that appear the same as clock signals and can produce false alarms or false indications of such clock signals.


A pulley is described for hauling strands of rope or chain and for engaging a splice coupling a strand of rope to a strand of chain. A plurality of pockets are arranged about the periphery of the pulley for positively engaging every other chain link. A plurality of pairs of rope-engaging surfaces are located between adjacent pockets and within the pockets. Rope and chain occupy substantially the same diameter of the pulley resulting in substantially the same speed and torque characteristics whether rope or chain is being hauled.

1. Field of the Invention
This invention relates generally to windlasses and, more particularly to windlass pulleys for hauling either rope or chain.
2. Description of the Related Art
Pulleys capable of handling both rope and chain are often used in windlasses for hauling anchors. In one prior art rope/chain pulley disclosed in U.S. Pat. No. 3,792,622, an outer channel of pockets or ribs drives the chain while an inner groove or sheave arrangement drives the rope. When the chain is driven on one diameter of the pulley and the rope is driven on a distinctly different diameter, significant speed and torque variations between the chain and the rope result.
Some prior art pulleys, such as that disclosed in U.S. Pat. No. 4,034,556 have a number of tooth formations which serve to engage both rope and chain. The number of tooth formations is fixed by the pulley diameter and the size of the chain to be hauled. This design is satisfactory for hauling chain, however, slippage may occur when rope is engaged with the pulley. Rope slippage results from limiting the number of rope-driving teeth to the number of chain-driving teeth.


A data processing apparatus includes a data processor core having integral cache memory and local memory, and external memory interface and a direct memory access unit. The direct memory access unit is connected to a single data interchange port of the data processor core and to an internal data interchange port of the external memory interface. The direct memory access unit transports data according to commands received from the data processor core to or from devices external to the data processing unit via the external memory interface. As an extension of this invention, a single direct memory access unit may serve a multiprocessing environment including plural data processor cores. The data processor core, external memory interface and direct memory access unit are preferably embodied in a single integrated circuit. The data processor core preferably includes an instruction cache for temporarily storing program instructions and a data cache for temporarily storing data. The data processor core requests direct memory access data transfers for cache service.

The technical field of this invention is data processing systems and particularly data processing systems with combined external memory access and direct memory access.
Data processing systems typically employ data caches or instruction caches to improve performance. A small amount of high speed memory is used as the cache. This cache memory is filled from main memory on an as needed basis. When the data processor requires data or an instruction, this is first sought from the cache memory. If the data or instruction sought is already stored in the cache memory, it is recalled faster than it could have been recalled from main memory. If the data or instruction sought is not stored in the cache memory, it is recalled from main memory for use and also stored in the corresponding cache. A performance improvement is achieved using cache memory based upon the principle of locality of reference. It is likely that the data or the instruction just sought by the data processor with be needed again in the near future. Use of cache memories speeds the accesses needed to service these future needs. A typical high performance data processor will include instruction cache, data cache or both on the same integrated circuit as the data processor core.
Conventional data processor cores typically include direct memory access (DMA). Direct memory access is a method of memory access not requiring data processor core activity, conventionally accomplished by a DMA functional block. This DMA functional block includes an I/O device and a controller function. This functional feature allows interface of external devices with the data processor core, internal memory, external memory, and other portions of the integrated circuit. The DMA interface is the communication link which relieves the data processor core from servicing these external devices on its own, preventing with loss of many data processor core cycles which would be consumed in a direct data processor core to external device interface.
The conventional direct memory access unit consists of a simple set of address generators which can perform reads and writes of some, or perhaps all, addresses within a data processing system. The address generation logic is normally implemented as a simple counter mechanism, with a reload capability from a set of data processor core memory-mapped registers. A typical use of a direct memory access unit is for the data processor core to load the counters with a starting address and a count, representing the amount of data to transfer. The data processor core must supply both the source and destination addresses for the transfer. Once this information has been loaded into the counters, the data processor can start the direct memory access via a memory mapped register write. The direct memory access unit then begins performing read and write accesses to move the requested data without further intervention from the data processor core. The data processor core is free to begin performing other tasks.
As the direct memory access unit performs read and writes to the source and destination locations, the addresses are incremented in each counter while the count is decremented. Once the count reaches zero, the transfer is complete and the direct memory access terminates. Most direct memory access units include a mechanism of signaling this complete state back to the data processor core via a status bit or interrupt. In general the interrupt method is preferred because it does not require a polling loop on the DSP to determine the completion status.
There are several features which are becoming increasingly common to direct memory access units which have attempted to address the issue of providing higher performance. The first is the inclusion of more DMA channels. A single DMA channel basically consists of all the hardware required to process a single direct memory access. This will generally include at least a source and destination address register/counter, a byte count register/counter, and the associated control logic to allow it to perform basic read and write operations. In a multi-channel direct memory access unit, the logic for a single channel is generally just replicated multiple times to provide increased channel capability. In addition to the multiple instantiations of the channels, a multi-channel direct memory access unit must also include some arbitration logic to provide time division access by all the channels to the memory/peripherals which the channels can address. Conventional direct memory access units may include from 2 to 16 channels. One advantage of additional channels is that each channel can contain parameters for a specific type of transfer. The data processor core sets up each channel in advance, and does not have to reload the direct memory access unit registers each time a new transfer has to be done, the way it would have to if only a single channel existed. Alternatively, a single direct memory access unit with plural channels may service plural data transfer requestors.
It is typical to provide a separate access port to the external memory interface for both the data processor core and for the direct memory access unit. The data processor core may directly request read or write data or instruction access from external memory via the external memory interface. Additionally, the data processor core makes cache service requests via the external memory interface. Cache service may also be reads or writes. The direct memory access unit may also make memory accesses, either reads or writes, under control of the data processor core via the external memory interface. This known technique requires the external memory interface to service two masters, the data processor core and the direct memory access unit.
This known technique encounters problems when extended to integrated circuits including plural data processor cores. According to this known technique, each of the plural data processor cores requires a port to the combined chip level external memory interface. In addition the external memory interface must be responsive to a combined chip level direct memory access unit. This configuration requires a lot of interconnect on the chip between the data processor cores and the external memory interface. In addition, this configuration is not easily scalable to accommodate additional data processor cores on the same integrated circuit. This is because each new data processor core requires another master port connection to the external memory interface.
This invention relates to a data processing apparatus. The data processing apparatus includes a data processor core having integral cache memory and local memory, and external memory interface and a direct memory access unit. The data processor core has a single data interchange port. The external memory interface has an internal data interchange port and an external data interchange port adapted for connection to devices external to the data processing apparatus. The direct memory access unit is connected to the single data interchange port of the data processor core and to the internal data interchange port of the external memory interface. The direct memory access unit transports data according to commands received from the data processor core to or from devices external to the data processing unit via the external memory interface. As an extension of this invention, a single direct memory access unit may serve a multiprocessing environment including plural data processor cores.
The data processor core, external memory interface and direct memory access unit are preferably embodied in a single integrated circuit. This single integrated circuit has the external interchange port of the external memory interface as its sole data port to external devices.
The data processor core preferably includes an instruction cache for temporarily storing program instructions and a data cache for temporarily storing data. The data processor core requests direct memory access data transfers for cache service such as: instruction cache fill upon a read access miss to the instruction cache; data cache fill upon a read access miss to the data cache; data writeback to system memory upon a write miss to the data cache; write data allocation to the data cache upon a write miss to the data cache; data writeback to system memory upon eviction of dirty data from the data cache.

Method and apparatus for operating one or more caches in conjunction with direct memory access controller


An alternating current (AC) to direct current (DC) converter device includes an AC-to-DC converter circuit, a step-down DC converter circuit, a controller, a first standby power converter circuit and a second standby power converter circuit. The AC-to-DC converter circuit is adapted to receive and perform an AC-to-DC conversion on an AC power so as to output a DC bus voltage. The step-down DC converter performs a step-down conversion on the DC bus voltage so as to output a main power voltage. The first standby power converter circuit performs a step-down conversion on the main power voltage so as to output a first standby DC voltage. The second standby power converter circuit performs a step-down conversion on the DC bus voltage to output a second standby DC voltage.

1. Field of the Invention
The invention relates to a power converter device, more particularly, an AC-to-DC converter device.
2. Description of the Related Art
With the electronic devices, such as home appliances, having intelligent features gaining great popularity, the use of standby power becomes an important topic. Standby power is the power needed when an electronic device is on standby (or, in idle) such as for maintaining a designated mode of operation, decreasing start up time, or waiting for a remote command. Standby power is different from main power needed for normal operation of the electronic device. The voltage level of standby power is usually substantially less than that of main power and needs to be generated separately.
FIGS. 1 and 2 show a conventional design of an offline AC-to-DC power converter 1 usually seen in electronic devices. The offline AC-to-DC power converter 1 includes an AC-to-DC power converter circuit 11, a step-down DC converter circuit 12, a standby power converter circuit 13 and a pulse-width modulation (PWM) signal generator 14. The AC-to-DC power converter circuit 11 converts an AC input voltage (90-264 Vac) into a DC bus voltage (VBUS) (380V). The step-down DC converter circuit 12 then performs a step-down conversion on the DC bus voltage (VBUS) so as to output a main voltage (VDC). The standby power converter circuit 13 performs a step-down conversion on the DC bus voltage (VBUS) so as to output a standby voltage (Vsb). The PWM signal generator 14 generates two PWM signals opposite in phase to respectively perform switching on a first switch (SW1) and a second switch (SW2) of the step-down DC converter circuit 12. When the electronic device operates in a normal mode, the step-down DC converter circuit 12 provides the main voltage (VDC) for operation. When the electronic device operates in a standby mode, the standby power converter circuit 13 provides the standby voltage (Vsb) for operation.
However, when the main voltage (VDC) and the standby voltage (Vsb) are both needed in the normal mode, the following happens. The standby power converter circuit 13 is an isolation type flyback converter circuit that receives the DC bus voltage (VBUS) and outputs the standby voltage (Vsb) and thus operates under high input/output potential difference. The load (hence the resistance) is substantially larger in the normal mode than in the standby mode. Where a large output is required under a large load, the presence of leakage inductance and distributed capacitance (from stray or parasitic components) will increase voltage and current surges, causing conversion loss, which becomes more evident as the load increases, and decreasing the stability of power provision.

Alternating current (AC) to direct current (DC) converter device


Remote differential compression is integrated within applications. Objects are updated between two or more computing devices using remote differential compression (RDC) techniques such that required data transfers are minimized. An algorithm provides enhanced efficiencies for allowing the receiver to locate a set of objects that are similar to the object that needs to be transferred from the sender. Once this set of similar objects has been found, the receiver may reuse any chunks from these objects during the RDC algorithm.

The proliferation of networks such as intranets, extranets, and the internet has lead to a large growth in the number of users that share information across wide networks. A maximum data transfer rate is associated with each physical network based on the bandwidth associated with the transmission medium as well as other infrastructure related limitations. As a result of limited network bandwidth, users can experience long delays in retrieving and transferring large amounts of data across the network.
Data compression techniques have become a popular way to transfer large amounts of data across a network with limited bandwidth. Data compression can be generally characterized as either lossless or lossy. Lossless compression involves the transformation of a data set such that an exact reproduction of the data set can be retrieved by applying a decompression transformation. Lossless compression is most often used to compact data, when an exact replica is required.
In the case where the recipient of a data object already has a previous, or older, version of that object, a lossless compression approach called Remote Differential Compression (RDC) may be used to determine and only transfer the differences between the new and the old versions of the object. Since an RDC transfer only involves communicating the observed differences between the new and old versions (for instance, in the case of files, file modification or last access dates, file attributes, or small changes to the file contents), the total amount of data transferred can be greatly reduced. RDC can be combined with another lossless compression algorithm to further reduce the network traffic. The benefits of RDC are most significant in the case where large objects need to be communicated frequently back and forth between computing devices and it is difficult or infeasible to maintain old copies of these objects, so that local differential algorithms cannot be used.

Applications for remote differential compression