A magnetic sensor having a coil that is not damaged by the injection pressure of a molten resin. The magnetic sensor includes a bobbin having a winding core and flanges, a supporting element connected to the bobbin, a coil for detecting a change in the magnetic field as a change in voltage, the coil including a winding wire wound around the winding core, an output lead wire of the coil being drawn out through an output lead slot formed in one of the flanges, and a housing covering outer portions of the bobbin, coil, and supporting element, wherein the output lead wire is drawn out through the output lead slot at a height, measured in a radial direction of the bobbin, which is substantially equal to a height of an outer surface of an adjacent portion of the supporting element.

1. Field of the Invention
The present invention relates to a magnetic sensor for detecting a change in magnetic field by detecting a corresponding change in voltage via a coil thereby detecting the position or the speed of revolution of an object.
2. Description of the Related Art
FIG. 13 is a cross-sectional view illustrating a conventional magnetic sensor in operation. FIG. 14 is a perspective view illustrating the general structure of the conventional magnetic sensor before being placed into a housing.
FIG. 15 is a cross-sectional view taken along line XV--XV of FIG. 14, and FIG. 16 is a cross-sectional view taken along line XVI--XVI of FIG. 15. The magnetic sensor 1 includes: a magnetic core 2; a bobbin 3 surrounding the magnetic core 2; a coil 4 consisting of a wire wound around the bobbin 3; a cylindrical supporting element 5 integrally connected to the bobbin 3; a magnet 6 in the form of, for example, a cylinder and a spacer 7 both placed inside the supporting element 5; a first electric terminal 8a and a second electric terminal 8b both protruding from the supporting element 5 in a radial direction; a tape 10 for pressing an input lead wire 9a and an output lead wire 9b of the coil 4 against the supporting element thereby fixing them to the supporting element 5; and a housing 11 in which the assembly 20 consisting of the above components 2, 3, 4, 5, 6, 7, 8a, 8b, and 10 are placed.
The bobbin 3 includes a winding core 15 around which the wire is wound, and flanges 12 disposed at either end of the winding core 15. One of the flanges 12 has an input lead slot 13 and an output lead slot 14 formed at locations opposite to the first electric terminal 8a and the second electric terminal 8b, respectively, wherein the input lead slot 13 and the output lead slot 14 extend in radial directions.
The process of producing the above magnetic sensor 1 is described below. First, the input lead wire 9a is put in through the input lead slot 13, and the wire is wound around the winding core 15 so as to form the coil 4 consisting of a plurality of wire layers. The output lead wire 9b extending from the outer periphery of the coil 4 is put out through the output lead slot 14 and is further placed on the supporting element 5 along its axis. The end of the input lead wire 9a is temporarily fixed to the first electric terminal 8a and the end of the output lead wire 9b is temporarily fixed to the second electric terminal 8b. The band-shaped fabric tape 10 is wound around the periphery of the supporting element 5 so that the input lead wire 9a and the output lead wire 9b are pressed against the supporting element 5 thereby fixing them to the supporting element 5. Then the end of the input lead wire 9a is firmly connected to the first electric terminal 8a by soldering. Similarly, the end of the output lead wire 9b is firmly connected to the second electric terminal 8b by soldering. The magnetic core 2 is placed into the bobbin 3, the magnet 6 and the spacer 7 are placed into the supporting element 5, and they are fixed together so that the complete assembly 20 is obtained.
The assembly 20 is then put in a mold, and a molten resin is injected into the mold so as to form the housing 11 surrounding the assembly 20 thereby obtaining the complete magnetic sensor 1.
In the magnetic sensor 1 described above, a magnetic path is formed such that a magnetic flux emerging from the magnet 6 passes through the magnetic core 2. When a signal detecting plate 16 having a projection 16a, made up of a magnetic material, is rotated, the distance between the magnetic sensor 1 and the signal detecting plate 16 varies with the rotation of the signal detecting plate 16. As a result, a change occurs in the magnetic flux emerging from the magnet 6. The change in the magnetic flux is detected as a change in voltage by the coil 4, and the signal detected by the coil 4 is transmitted to a computer unit(not shown) so that the speed of revolution of the signal detecting plate 16 is determined.
The conventional magnetic sensor 1 described above has the following problems. In order to achieve a high enough voltage for the detection signal of the magnetic sensor 1, the wire has to be wrapped around the winding core 15 many times. As a result, as shown in FIG. 15, the radius X.sub.1 of the coil 4 generally becomes greater than the radius X.sub.2 of the supporting element 5 and thus a difference in level is created between the outer periphery of the coil 4 and the outer periphery of the supporting element 5. This difference in level causes the output lead wire 9b, which extends though the output lead slot 14 and further extends along the axis of the supporting element 5, to have an oblique portion 9b.sub.1 extending away from the supporting element 5. Since this oblique portion 9b.sub.1 is separate from the outer periphery of the supporting element 5, the oblique part 9b.sub.1 by itself should withstand the injection pressure of the molten resin when the molten resin is injected into the mold to form the housing 11. As a result, great tensile stress is imparted to the output lead wire 9b, which can damage the coil 4.
It is desirable that the thickness of the flanges 12 be small enough so that the total length of the magnetic sensor 1 becomes small and the tape 10 can have a large pressing area. However, the thickness of the flanges 12 should be greater than about 1 mm so that the flanges 12 can withstand the injection pressure of the molten resin. One of the flanges 12 has the output lead slot 14 having a corner perpendicular to the winding direction of the winding wire of the coil 4. When the output lead wire 9b comes in contact with the right-angle corner, the output lead wire 9b can be damaged.
In view of the above, it is a general object of the present invention to solve the above problems.
More specifically, it is an object of the present invention to provide a magnetic sensor in which a coil does not become damaged due to the injection pressure of a molten resin.
It is an another object of the present invention to provide a magnetic sensor in which an output lead wire can be drawn out through an output lead slot without becoming damaged due to contact with a corner of the output lead slot.

Magnetic sensor with supporting element for supporting output lead wire of coil


The cell enhancing device for an electrical pulse cosmetic meter, wherein the composite pulse generating device comprising an electrical pulse generating device, generating an electrical pulse sequence of a predetermined electrical pulse amplitude, wherein a frequency of said electrical pulse sequence is adjustable, a waveform adjuster, converting said electrical pulse sequence to a composite pulse sequence, and outputting said composite pulse sequence to a cosmetic head of said electrical pulse cosmetic meter. The present invention has the advantages of being small in size and light in weight. Furthermore, it greatly enhances circulation in skin structure of body, so as to achieve effective cosmetic results.

1. Field of Invention
The present invention relates to a device for enhancing cell metabolism, and more particularly to a composite pulse generating device for an electrical pulse cosmetic meter, wherein the composite pulse generating device comprising an electrical pulse generating unit, a waveform adjuster and a treatment body. The waveform adjuster converts an electrical pulse sequence produced by the electrical pulse generating device to a composite pulse sequence, and outputs the composite pulse sequence to the cosmetic head. The frequency of the composite pulse sequence matches with the natural frequency of a cardiovascular cycle. As a result the vibration frequencies of cells are tuned to that of the cardiovascular cycle, such that blood flow is enhanced.
2. Description of Related Arts
Body metabolism rate slows down with age. This slowing down of metabolism will show in all aspects of the body, including deterioration in health, energy level, gaining in weight and so on. It is, however, most noticeable on the skin.
Water and impulses from nerves are essential for skin cells to stay alive. Water is the main constituent of blood, which bring nutrients to all living cells. Impulses are produced by nerves connecting to the brain, which provides instructions and controls activities in cells. When in lack of either one of them, skin cells die off.
Many research shows that aging is related to an increasing production of oxidative free radicals. Such oxidative free radicals are, in turn, related to many health problems associated with aging, such as higher chances of getting Caners, atherosclerosis, heart disease and many other chronic diseases. They are substances produced by the mitochondria respiration in a cell. The older an individual, the more oxidative free radicals are produced.
The slowing down of metabolism is controlled by three factors, the first being the body genes, which acts as a program to the body's biological clock. The second is the person's subconscious, which is affect by the surrounding environment. The third is damaged cells or organs, which ability of renewing dead cells deteriorates.
When metabolism rate slows down, it means that body cells die off at a higher rate than they can be regenerated. In the case of skin cells, the rate of new skin cells being created are not as high as that of cells dying off. As a result, wrinkles appear on the skin.
Wrinkles is the most obvious indication of aging, which is the reason why people are very willing to pay hundreds and thousands of dollars on facial treatments to prevent getting or in the hope of getting rid of wrinkles. All sorts of creams and treatment lotions are produced claiming their miraculous effects on wrinkles and skin conditions. However, their results are questionable.
Others would even go as far as having cosmetic surgeries, such as having a face lift, to smoothen their wrinkles. Despite how safe cosmetic surgeons claim, all surgeries have risks. And, in general, they are all very costly. Furthermore, such wrinkle removing treatments and surgeries can only remove wrinkles and cannot prevent the reoccurrence of wrinkles or improve on the skin conditions after removing the wrinkles. As a result, such treatments and surgeries are only temporary. The fundamentals of the occurrence of wrinkles are not being dealt with.
As a result, in order to prevent or remove wrinkles in a safer, more effective, more cost effective and convenient manner, better treatments that can deal with the causes of wrinkles has to be provided.


Compositions are provided to immobilize and protect oxidase enzymes from proteolytic and hydrolytic attack, utilizing a porous, inert organic, or inorganic, substrate matrix useful in generating hydrogen peroxide in situ for use in oral, topical mucosal and intracavity uses for use in or on the human body and other mammalian, reptile, fish and amphibians.

Hydrogen Peroxide
Hydrogen peroxide, or H2O2, is naturally found in human cells and is used for disinfection. Hydrogen peroxide has anti-fungal, anti-bacterial, anti-parasitic and anti-viral activity. Once hydrogen peroxide interacts with certain enzymes, catalase or peroxidase, it yields water and an oxygen ion. Two singlet oxygen ions make stable oxygen, O2.
The bacterial origin of dental disease is well established. Dental caries, gingivitis and halitosis are all associated with resident oral bacteria. Reduction in their number by germicidal agents is a current aim to control these oral conditions. Glucose oxidase, a flavo-enzyme (GLU-OXY), is known to act upon a glucose substrate to produce hydrogen peroxide and gluconic acid. Since the mouth also contains highly active proteases, any additional oxidase enzyme can be rapidly inactivated by proteolytic action of these protease enzymes.
Glucose oxidase (B-D-glucose: oxygen I-oxidoreductase. ECI.1.3.4.) flavoenzyme is widely used for the determination of glucose in body fluids, and in removing residual glucose and oxygen from beverages and foodstuffs. See William. D. C., or al Clin. Chem. 22, 372, 1976. Furthermore, glucose oxidase-producing molds, such as Aspergillus and Penicillium species, have been used for the biological production of gluconic acid, as well as the oxidase. A unit is defined as the enzyme amount which causes oxidation of one micromole of glucose per minute at 25 C and pH 7.0.
Glucose oxidase combined with an appropriate cofactor catalyses the oxidation of R-D-glucose to D-glucono-1, 5-lactone and hydrogen peroxide, using molecular oxygen as the electron acceptor. The pH range is from 4 to 7, with an optimum pH at 5.5. The enzyme, GLU-OXY, is a dimeric holoprotein with a molecular weight of 160 (KDA 160.000 Daltons), containing one tightly bound (Kw 1×10-10) flavin adenine dinueleotide (FAD) per monomer, as cofactor. The FAD is not covalently bound and so can be released from the holoprotein following denaturation.
The human oral cavity° is known to contain other highly active proteolytic enzymes, known as proteases, and concurrently, the afore-described glucose oxidase. The latter is useful to act upon glucose to produce gluconic acid and hydrogen peroxide. The peroxide, in turn, is known to be converted by oral catalase to oxygen and water. The liberated oxygen has a germicidal effect upon the oral cavity. If the oral GLU-OXY concentration is increased, for example, by addition to a dentifrice, the proteolytic enzymes will interfere with enhanced level of glucose oxidase enzyme, by destroying the glucose oxidase. So, there is a need to protect glucose oxidase from the ever present oral proteolytic enzymes. The same utility of Glucose Oxidase can be found in the mucosa, in open wounds and within other body cavities such as the vagina, the nasal and auditory canal, the urethra and induced opening such as venous punctures.
Proteolytic enzymes are large group of natural proteins (polypeptides) with a peptide chain coiled to form an alpha-helix, and which display enzymatic activity; that is, they catalyze specific organic, or even inorganic, reactions. A typical proteolytic protein-splitting enzyme is alpha-chymotrypsin of a molecular weight c.25,000. It has a quite general power of affecting the hydrolysis of carboxyl derivatives, amides, esters, and hydrazides.
Attempts to exploit these natural antimicrobial systems have been directed to both the oral care field and the gastrointestinal tract. U.S. Pat. No. 4,150,113 and U.S. Pat. No. 4,178,362 (Hoogendom, et al) describe dentifrice compositions containing glucose oxidase, that react with plaque and salivary glucose to produce low levels of hydrogen peroxide. Hydrogen peroxide production by such systems is however, highly irregular, due to the non-uniform distribution and unpredictable availability of substrate, namely glucose, in the oral cavity, and instability of the enzyme in the presence of proteases. The effects are described as transient due to the inherent instability of the glucose Oxidase enzyme.
U.S. Pat. No. 4,269,822. U.S. Pat. No. 4,564,519, and U.S. Pat. No. 4,578,265 (Pellico, etal) further describe dentifrice compositions containing an oxido-reductase enzyme and its specific substrate in an aqueous solution for the purpose of producing in the oral cavity hydrogen peroxide or other antimicrobial oxidizing compounds such as hypothiocyanite ion. A more predictable amount of hydrogen peroxide (and subsequently hypothiocyanite ions) is produced by the compositions of Pellico et al, compared with those of the Hoogendorn references (U.S. Pat. Nos. 4,150,113 and 4,178,362). The differences between the two compositions reflect the availability of glucose in the oral cavity as substrate for glucose oxidase.
U.S. Pat. No. 4,564,519 describes a chewable dentifrice, such as a chewing gum or lozenge, which contains a dual enzymes system for producing hypothiocyanite ions upon being chewed or otherwise activated by the moisture in saliva. Such compositions stiffer from similar drawbacks to those mentioned immediately above, namely a slow rate of enzymatically-produced hydrogen peroxidase as well as a reliance on a cariogenic compound.
The formation of calculus and dental plaque is the primary source of gingivitis, dental caries, periodontal disease, tooth staining and tooth loss.
Dental calculus, or tartar as it is sometimes called, is a deposit, which forms on the surfaces of the teeth at the gingival margin. Mature calculus consists of an inorganic portion which is largely calcium phosphate arranged in a by hydroxyapatite crystal lattice structure similar to bone, enamel and dentine. An organic portion is also present and consists of desquamated epithelial cells, leukocytes, salivary sediment, food debris and other various types, unless stained or discolored by some extraneous agent. In addition to being unsightly and undesirable from an aesthetic standpoint, the mature calculus deposits are constant sources of irritation of the gingiva,
Plaque can be defined as a complex microbial community, with bacteria comprising approximately 70-80% of the plaque matrix. It has been estimated that as many as 400 distinct bacterial species may be found in plaque. This mix includes both aerobic and anaerobic bacteria, fungi, and protozoa. Viruses have also been found in samples of dental plaque. In addition to the bacterial cells, plaque contains a small number of epithelial cells, leukocytes, and macrophages. The cells are contained within an extra cellular matrix, which is formed from bacterial products and saliva. The extra cellular matrix contains protein, polysaccharide and lipids. This matrix of organisms and oral exudates continues expanding and coalesces with other plaque growths situated nearby. The bacteria synthesize levans and glucans from sucrose found in the oral cavity providing energy for the microorganisms. These glucans, levans, and microorganisms form an adhesive skeleton for the continued proliferation of plaque.
Retarding and/or stopping the proliferation of plaque and calculus are critical to maintaining good oral health. Plaque and calculus formation may lead to dental caries, gingival inflammation, periodontal disease, and ultimately tooth loss. Additionally, calculus and plaque along with behavioral and environmental factors lead to formation of dental stains, significantly affecting the aesthetic appearance of teeth. Behavioral and environmental factors that contribute to teeth staining propensity include regular use of coffee, tea, wine, cola or tobacco products.
Plaque has been classified by association with disease state as "health-associated" or "disease associated". The latter classification is related to differences in the microbial composition of dental plaque in health versus disease. A newly cleaned tooth surface is rapidly covered with a glycoprotein deposit referred to as "pellicle". The pellicle is derived from salivary constituents which are selectively adsorbed onto the tooth surface. The formation of pellicle is the first step in plaque formation.
The pellicle-coated tooth surface is colonized by Gram-positive bacteria such as Streptococcus sanguts, Streptococcus mutans, and Aetinornyces viscosus. These organisms are examples of the "primary colonizers" of dental plaque. Bacterial surface molecules interact with components of the dental pellicle to enable the bacteria to attach or adhere to the pellicle-coated tooth surface. Within a short time after cleaning a tooth, these Gram-positive species may be found on the tooth surface. After the initial colonization of the tooth surface, plaque increases by two distinct mechanisms: 1) the multiplication of bacteria already attached to the tooth surface, and 2) the subsequent attachment and multiplication of new bacterial species to cells of bacteria already present in the plaque mass. These new bacteria include anaerobic Grain-negative species such as Fusobacterium nucleatum and Prevotella intetnzedia; and the Capnocytophaga species. The overall pattern observed in dental plaque development is a very characteristic shift from the early predominance of Grain-positive facultative microorganisms to the later predominance of Gram-negative anaerobic microorganisms, as the plaque mass accumulates and matures. This developmental progression is also reflected in the shifts in predominant microorganisms that are observed in the transition from health to disease. Studies of plaque taken from sites of health or disease and examined either microscopically or by culturing have demonstrated distinct differences in health versus disease-associated microbial populations.
Halitosis has also been an unsolved physiological problem for centuries, and remains as such in the modern era. Halitosis is the technical term for bad breath, a condition estimated to affect 50 to 65% of the population. Up to 90% of cases are thought to originate from sources in the mouth, including poor oral hygiene, periodontal disease, coating on the tongue, impacted food, faulty dental restoration, and throat infection. The chemical basis of halitosis lies in the concentration of mouth-bound volatile and odiferous compounds, primarily organic and inorganic sulfides as well as organic amines. These odiferous volatiles are biologically synthesized by particular microorganisms that reside in the oral cavity. Halitosis is primarily caused by certain anaerobic strains of bacteria (Rosemberg, M., Bad Breath: Research Perspectives. Rumor Publishing, 1995). Specifically, the proliferation in saliva of the anaerobic bacterial pathogen Fusobacterium Species, in combination with other anaerobes, has been shown as the major biological source of halitosis.
Factors that support the growth of these bacteria will predispose a person to halitosis. Examples include accumulation of food within pockets around the teeth, among the bumps at the back of the tongue, or in small pockets in the tonsils; sloughed cells from the mouth; and diminished saliva flow. Mucus in the throat or sinuses can also serve as a breeding ground for bacteria. Conditions are most favorable for odor production during the night and between meals.
Although bad breath primarily represents a source of embarrassment or annoyance, research has shown that the sulfur gases most responsible for halitosis (hydrogen sulfide and methyl mercaptan) are also potentially damaging to the tissues in the mouth, and can lead to periodontal disease (a bacterial infection of the gains and ligaments supporting the teeth). As periodontal disease progresses, so may the halitosis, as bacteria accumulate in the pockets that form next to the teeth.
The ultimate oral cleaning level is what dentists provide during prophylaxis; daily oral care at home requires products with multiple ingredients working by different mechanisms to provide satisfactory cleaning and whitening, Oral care products for daily use such as dentifrice and rinses provide overall cleaning, but it is necessary to add ingredients for provision of anti-plaque and anti calculus benefits as well as breath freshening, stain removal, stain control and tooth whitening. Such ingredients for removal and control of stain and for whitening include bleaches, abrasives or chemical chelants. Bleaches added to dentifrices are typically present in low concentrations due to stability and safety limits unique to toothpastes. At these low concentrations bleaches, typically oxidizing agents, are generally ineffective at tooth whitening and stain control. Dental abrasives provide whitening benefits on 'brushed' areas of teeth, but unfortunately are of limited effect in controlling aesthetically undesirable stains that Joint along the gumline and interproximally.
Although products containing chemical oxidizing agents and other plaque and calculus reduction agents are known, there is a continuing need to develop improved products, in particular products that provide enhanced overall cleaning by concurrently attacking the calculus, plaque, and staining problems.
Attempts to exploit these natural antimicrobial systems have been directed to both the oral care field and the gastrointestinal tract. U.S. Pat. No. 4,150,113 and U.S. Pat. No. 4,178,362 (Hoogendom, et al) describe dentifrice compositions containing glucose oxidase, that react with plaque and salivary glucose to produce low levels of hydrogen peroxide. Hydrogen peroxide production by such systems is, however, highly irregular, due to the non-uniform distribution and unpredictable availability of substrate, namely glucose in the oral cavity and instability of the enzyme in the presence of protease.
U.S. Pat. No. 4,269,822, U.S. Pat. No. 4,564,519, and U.S. Pat. No. 4,578,265 (Pellico, et at) further describe dentifrice compositions containing an oxidoreductase enzyme and its specific substrate in an aqueous solution for the purpose of producing in the oral cavity hydrogen peroxide or other antimicrobial oxidizing compounds such as hypothiocyanite ion. A more predictable amount of hydrogen peroxide (and subsequently hypothiocyanite ions) is produced by the compositions of Pellico et al, compared with those of the Hoogendom references (U.S. Pat. Nos. 4,150,113 and 4,178,362). The differences between the two compositions reflect the availability of glucose in the oral cavity as substrate for glucose oxidase.                U.S. Pat. No. 4,564,519 describes a chewable dentifrice, such as a chewing gum or lozenge, which contains a dual enzymes system for producing hypothiocyanite ions upon being chewed or otherwise activated by the moisture in saliva. Such compositions suffer from similar drawbacks to those mentioned immediately above, namely, a slow rate of enzymatically-produced hydrogen peroxidase as well as a reliance on a cariogenic compound.Background Oral Proteases
The oral cavity contains many specific and non-specific proteases, both endogenous and exogenous. Exogenous types are from both viral and bacterial sources, while endogenous protease are mainly secreted by salivary glands. Some of these proteases include: three enzymes including leucine amino peptidase, dipeptidyl peptidase IV and trypsin-like proteinase, salivary matrix metalloproteinases (MMPs) (may participate in the pathogenesis of mucosal lesions and dentinal caries), particularly activity of MMP- (collagenase-2) and MMP-9 (gelatinase B), cysteine peptidases, aminopeptidase, neuropeptide-degrading enzymes and secreted aspartic proteases (Saps) These enzymes destroy a wide variety of proteins, including other enzymes.
Degradation of Glucose Oxidase by Salivary Proteases
Glucose oxidase in the presence of glucose and oxygen will convert glucose to hydrogen peroxide and gluconic acid at a fast rate, (GOx from Aspergillus nigec Michaelis constant KM 33 The Michaelis constant Kin is defined as the substrate concentration at ½ the maximum velocity) By measuring the oxygen consumption the reaction rate can be followed by using a Clark oxygen electrode. Three test cells were set up containing five milligrams of the enzyme in 10 ml of saline at pH 7.0. Test cell one contained only saline and enzyme, cell two contained enzyme plus five milligrams of commercial bacterial protease from Bacillus polymyra (1 unit/milligram), and cell three contained glucose oxidase enzyme plus two milliliter of human saliva. The cells were incubated qt 37 degrees Centigrade for 10 minutes. Two hundred millimoles of glucose were then added to each cell and the oxygen consumption measured over five minutes.
Results
Cell one showed 52% of the oxygen consumed in 5 minutes, cell two showed 10% of the oxygen consumed in five minutes and cell three showed 8% of the oxygen consumed in five minutes. These results confirmed the degradation of glucose oxidase by oral proteases.
Immobilized Glucose Oxidase Protection from Salivary Protease
Immobilization of enzymes is an established procedure in biochemistry, many factors affect the choice of substrate on which to fix the enzyme, it is often convenient to immobilize the enzyme on a support material by adsorption, deposition or a chemical means. Useful supports are porous glass, celite, porous hydrophobic resins and ion exchange materials. Depending on the properties of the support (particle size, pore size, etc) and other parameters, the enzyme loading is variable. In addition the solvent can affect the enzyme catalyzed reaction by influencing the solvation of the substrates and products or by direct interaction with the enzyme. Water is the main solvent in saliva.
Effects of the Water Content
Even in biocatalytic systems which contain mainly organic solvent and/or organic substrates, the catalytic activity is highly dependent on the amount of water present. The amount of water is best quantified in terms of water activity since the water activity is correlated with the hydration of the enzyme which in turn governs the catalytic activity. Salvia is 90+% water, so we can consider the solvent system as water.

Immobilized glucose oxidase for use in oral hygiene

Abstract: The selected porosity of the support matrix provides the basis for generating hydrogen peroxide on a steady state basis. Both diatomaceous earth and silica gel, either in natural or pre-silanized forms, allow for the excluding of non-preferred enzymes from the support matrix, and for diffusion of the peroxide in the reduction of oral pathogens and their attendant malodorous compounds, or other pathogens in the mucosa, bodily fluids and cavities, in addition to oxidizing color bodies to affect bleaching.


An optical multiplex communication system includes a transmission part and a receiving part, wherein the transmission part includes a transmission quality detecting part which measures and transmits a transmission quality information for the channels based on a request from the transmission part; the receiving part includes a variable optical attenuation part controls the optical signal level for the channels, an optical level setting part controls the variable optical attenuation part based on a setting value, a setting control part adding the setting value to the optical level setting part based on a request for setting.

1. Field of the Invention
The present invention relates to an optical multiplex communication system and an optical transmission apparatus having a transmission part and a receiving part, and a control method of optical multiplex communication by which multiplexed optical signals are controlled to be transmitted stably.
2. Description of the Related Art
A wavelength division multiplexing (WDM) transmission method is known as a transmission means for transmitting a large amount of information at a high speed. In the WDM transmission method, the optical signals having different wavelengths are respectively assigned to a plurality of channels, so that the optical signals are multiplexed and transmitted to one optical transmission path. In this case, at a transmission part, the optical signals having different wavelengths are multiplexed, amplified by an optical amplifier such as an Er doped optical fiber, and then transmitted to the optical transmission path. A relay amplifier or an end amplifier consists of an optical amplifier similar to the above mentioned amplifier so that the optical signal is amplified. The optical signals that are multiplexed are de-multiplexed for respective channels so that the receiving process is implemented at the receiving part.
The optical amplifier amplifying the optical signal that is multiplexed generally has an ALC structure in which a feedback control is implemented so that an amplified output optical level has a designated value. In this case, it is necessary to demultiplex the optical signal level for respective channels having designated levels. Hence, the optical amplifier is controlled for the number of channel. In a case where the optical signal that is multiplexed is amplified and transmitted, an optical signal level of other channel changes based on an increase/decrease of the number of channels or a change of the optical signal level of one channel.
With respect to a received optical signal of the receiving part, which is influenced by the transmission property of the optical signal that is multiplexed, including the optical amplifier and the optical transmission path, a means for adjusting the optical signal power of respective channels at a receiving side so that the respective optical signal power of the respective channels become the same is known. See the Japanese Laid-Open Patent Application No. 6-69891.
In addition, a multiplex optical communication system, in which an optical amplifier amplifying the optical signal that is multiplexed is controlled based on a change of the number of channels so that the respective optical signal power of the respective channels at the receiving part becomes the same and the control process is made smooth, is known. See the Japanese Laid-Open,Patent Application No. 8-195733.
Furthermore, a system, in which variations in the number of channels are detected and the time needed to control an optical amplifier and the time needed to input a multiplexed optical signals having the channel number varied to the optical amplifier are adjusted so as to reduce variations of optical signal power of respective channels at a receiving part, is known. See the Japanese Laid-Open Patent Application No. 2001-53682.
At the receiving part of the optical multiplex communication system in which the optical signals having different wavelengths are respectively assigned to a plurality of channels and multiplexed so as to be amplified and transmitted, it is necessary that the optical signal levels of respective channels have more than designated values in order to reduce an error of the receiving process. Hence, transmission quality information such as the optical signal level for respective channels at the receiving part or an error ratio is provided to the receiving part. Furthermore, a means for controlling the optical signal levels that are multiplexed for respective channels based on the transmission quality information from the receiving part can be applied to the receiving part.
However, in a case where the transmission quality information for respective channels is provided from the receiving part to the transmission part, there is a problem. That is, a control of the optical signal levels for respective channels at the receiving part based on the above mentioned transmission quality information may be delayed at a path for the above mentioned control. Because of this, the optical signal levels that are multiplexed may change greatly so that the optical signal levels of other channels are influenced and the whole of the transmission quality may decline. Furthermore, in a case where the optical signal levels for respective channels becomes large wholly and the input power of the optitcal amplifier of the transmission part increases, if the optical signal levels for respective channels are reduced evenly, the transmission qualities of all of the channels are reduced. Because of this, level controls against the optical signal of the respective signals based on the transmission quality occur frequently so that an automatic level control at the optical amplifier becomes unstable and time for convergence becomes long. As a result of this, the change of the qualities of respective channels may occur.

Optical multiplex communication system, optical transmission apparatus, and control method of optical multiplex communication


An assembly for producing sealed packaging units (14) from a sheet packaging material, comprises: an advancement device (21) for advancing the sheet packaging material along an advancement direction (F), a longitudinal sealing device for sealing opposite borders of the sheet packaging material along a longitudinal sealing band arranged parallelly to the advancement direction (F), thereby forming a continuous tube (15), a transverse sealing device (29) for sealing the continuous tube (15) transversely to the advancement direction (F), so as to define a sealed packaging unit (14). The transverse sealing device (29) comprises a sealing element (30) and an abutment element (31) that are intended to mutually cooperate during sealing while being located on opposite sides of the continuous tube (15). The sealing element (30) is so configured as to act on a side (27) of the continuous tube (15) on which the longitudinal sealing band is provided.

As is known, many pourable food products, such as fruit juice, UHT (ultra-high-temperature treated) milk, wine, tomato sauce, etc., are sold in packages made of sheet packaging material.
For example, parallelepiped-shaped packages for liquid or pourable food products are known, which are made by folding and sealing laminated sheet packaging material. The packaging material has a multilayer structure comprising a base layer, e.g. of paper, covered on both sides with layers of heat-sealable plastic material, e.g. polyethylene. In the case of aseptic packages for long-storage products, such as UHT milk, the packaging material also comprises a layer of oxygen-barrier material, e.g. an aluminium foil, which is superimposed on a layer of heat-sealable plastic material, and is in turn covered with another layer of heat-sealable plastic material forming the inner face of the package eventually contacting the food product.
The package is produced starting from a basic unit of packaging material, which is normally conformed as a portion of a sheet of packaging material advanced through a packaging machine along an advancement direction.
If there is the need to produce a sterilized package, the sheet of packaging material is sterilized on the packaging machine, and subsequently maintained in a closed, sterile environment.
In any event, opposite longitudinal borders of the sheet packaging material are sealed together along a longitudinal sealing band to form a continuous tube, which is filled with the desired product.
The tube is advanced on the packaging machine by a plurality of pairs of jaws. Each pair of jaws is provided with a transverse sealing device for sealing the tube along a transverse sealing band arranged transversely to the advancement direction. In particular, the transverse sealing device comprises a sealing element interacting with the sheet packaging material in order to seal opposite ends of the sheet packaging material along the transverse sealing band and an abutment element, opposite the sealing element, against which the sheet packaging material is pressed during sealing. When the packaging material forming the continuous tube is clamped between the abutment element and the sealing element, the abutment element faces a side of the continuous tube on which the longitudinal sealing band is obtained. The sealing element faces the other side of the continuous tube, i.e. the side that is free of the longitudinal sealing band.
In certain cases, the containers described above can be provided with respective reclosable opening devices made of plastic material. A reclosable opening device comprises a pouring spout, defining a through pouring opening and fitted to a hole in a top wall of the container. The pouring spout has a neck, for example threaded, which during use protrudes from the top wall. A removable lid, e.g. a screw lid, is subsequently fitted to the pouring spout in order to outwardly close the latter.
The pouring spout is applied onto the sheet packaging material as the latter is advanced through the packaging machine, before longitudinally sealing the sheet packaging material to obtain the continuous tube therefrom. The pouring spout may be, for example, moulded on the sheet packaging material before folding the latter.
Hence, when the transverse sealing device interacts with the sheet packaging material, the latter is already provided with a plurality of pouring spouts. In particular, the pouring spouts are applied to the side of the continuous tube opposite the further side of the continuous tube provided with the longitudinal sealing band, i.e. on a portion of the sheet packaging material facing the transverse sealing element.
When a continuous tube provided with the pouring spouts is to be sealed by the transverse sealing device, the neck of each pouring spout may interfere with the sealing element. If this occurs, the sealing element may deform the neck or even break the latter, which makes it difficult if not impossible to apply the lid on the neck on a subsequent capping machine.
In case interference occurs between the neck and the sealing element, also the package may be damaged due to excessive pressures applied thereto.
In order to avoid these risks, it has been thought to obtain on the sealing element of the transverse sealing device a recess for housing the neck while the continuous tube is being sealed transversely to the advancement direction. However, this solution cannot be adopted on all kinds of packaging machines. For example, if the packaging machine is provided with a transverse sealing device of an ultrasonic type, the sealing element is a sonotrode that needs to have a minimum vibrating mass in order to ensure proper sealing of the sheet packaging material. In this case, providing a recess on the sealing element, which decreases the mass thereof, may jeopardize tightness of the transverse sealing band.
More in general, providing a recess on certain kinds of sealing elements may be difficult since it would excessively complicate the structure of the sealing element.

Assembly for producing sealed packaging units


An apparatus for separation or synthesis of process substances is configured with at least two cell stacks, within each of which there is arranged at least one large-area layer for the separation or synthesis and passages are formed for feeding and discharging at least one process substance to or from the at least one layer. To ensure that the ratio of active surface area to total area of the layer is as high as possible yet on the other hand that uniform distribution of at least one process substance over the layer are ensured, at least two passages for a process substance are formed within at least a first cell stack, of which a first passage is used to pass the process substance through the first cell stack to a second cell stack and of which the second passage is used to feed or discharge the process substance to or from the at least one layer in the first cell stack.

Apparatuses of the above type are used for substance separation or substance synthesis processes in which, for example, two process spaces are separated from one another by a partially permeable large-area layer, for example in the form of a membrane. For example, in the case of synthesis processes of a PEM fuel cell, the process spaces are separated from one another by selectively permeable layers, in particular membranes. The layers or membranes are in this case predominantly permeable to ions which are used for charge transfer.
In a cell stack of an apparatus of this type, passages for routing process substances penetrate through the selectively permeable layers in the interior of the cell stack. The layers are sealed at their outer edge and at their edges adjoining the passages.
A certain minimum surface area of membrane or layers has to be made available for the desired chemical or electrochemical separation or synthesis process. The consumption of surface area and therefore of layer material is increased by the fact that the passages and their seals are routed through the layers. However, the material required to produce the layer, in particular in the case of PEM fuel cells, is relatively expensive. Therefore, it is fundamentally the aim for only small amounts of such material to be installed in the apparatus.
Apparatuses with high process flows require relatively large passage cross sections within the layers, and consequently the desired cost objectives cannot be achieved, on account of the large amount of material cut from the layers.
In addition to efficient utilization of the material of the layers, it is also a requirement for the individual process substance to be distributed uniformly over the area of the layers in the cell stack. Furthermore, the overall pressure loss in the passages for feeding and discharging the individual process substance should be as low as possible.
U.S. Pat. No. 5,484,666 A has disclosed a cell stack of an electrochemical cell in which feed and discharge passages are routed through a multiplicity of membranes. This keeps the total volume of the cell stack relatively small, but the amount of material cut from the membranes for the passages is large. Furthermore, tie rods for connecting and clamping the cell stack are formed through the passages in the cell stack. The tie rods are supported on front and end plates of the cell stack, in which connections for the passages are also formed.
U.S. Pat. No. 5,543,240 A has disclosed an overall fuel cell stack in which a process substance is routed to individual cell stacks through external supply passages. The external supply requires additional components, and in particular valves for connection to the cell stacks, and makes it more difficult to achieve a space-saving and inexpensive design of the overall fuel cell stack.

Apparatus for seperation or synthesis of process substances


A medical composition for reducing the rate of new-onset diabetes caused by administration of a statin or for inhibiting an increase in blood glucose level by administration of a statin, the composition containing at least one ingredient selected from the group consisting of icosapentaenoic acid and pharmaceutically acceptable salts or esters thereof as an inactive ingredient.

Dyslipidemia is a large risk factor of arteriosclerosis, and arteriosclerosis is the cause of coronary artery diseases such as angina pectoris and myocardial infarction and cerebral stroke such as cerebral hemorrhage and cerebral infarction which are major death causes of Japanese. In the meanwhile, it has been demonstrated that these cardiovascular diseases can be prevented and treated by treating such dyslipidemia.
According to the diagnostic criteria of Atherosclerotic Diseases Prevention Guideline (2012), dyslipidemia is divided into hyper-LDL cholesterolemia (LDL cholesterol (hereinafter also referred to as "LDL-C") 140 mg/dL), borderline hyper-LDL-cholesterolemia (LDL-C, 120 to 139 mg/dL), low HDL cholesterolemia (HDL cholesterol (hereinafter also referred to as "HDL-C")<40 mg/dL), and hypertriglyceridemia (triglyceride (hereinafter also referred to as "TG")≧150 mg/dL). Recently, the hyper-LDL cholesterolemia, the low HDL-cholesterolemia, and the hypertriglyceridemia are conceived as independent risk factors.
The therapeutic agent used for the dyslipidemia differs by the type of the dyslipidemia, and statin is the first choice for treating the hyper-LDL-cholesterolemia. Statin acts in mevalonic acid synthetic pathway wherein biosynthesis of isopentenyl diphosphoric acid and dimethyl allyl diphosphoric acid (starting materials of steroid synthesis) from acetyl CoA takes place by inhibiting HMG-CoA reductase (EC 126.96.36.199) (hereinafter also referred to as "HMG-CoA") which is an enzyme catalyzing the reaction of reducing hydroxymethyl glutaryl CoA to mevalonic acid, and thereby suppressing the biosynthesis of the cholesterol. The thus reduced cholesterol biosynthesis also invites effects such as enhanced expression of liver LDL (low density lipoprotein) receptor, increased incorporation of LDL-C from the blood into the liver, suppressed VLDL (very low density lipoprotein) secretion into the blood, and reduced serum TG and increased HDL-C. In view of such function of the statin, statin is also referred to as HMG-CoA reductase inhibitor (HMG-CoA RI).
Statin is effective for the treatment of cardiovascular diseases and prevention of cardiovascular events, and statin has been considered to be a safe drug with high tolerability. However, recent reports indicate relation between the statin and the risk of diabetes incidence. For example, Non-Patent Document 1 discloses that, in the general evaluation conducted by collecting the results of 16 clinical trials wherein participants were divided into the group administered with statin (lipid lowering drug) and the group not administered with the statin, the risk of diabetes incidence was 9% higher in the group administered with the statin. In addition, United States Food and Drug Administration announced a safety communication on the increase of blood glucose and risk of type 2 diabetes incidence by the statin administration in February, 2012, and the package insert of the statin preparation now includes the description that the statin administration invited an increase of hemoglobin Alc (hereinafter also referred to as "HbAlc") and fasting blood glucose and significant increase in the diabetes incidence (Non-Patent Document 2). However, it has been conceived, even if the risk of diabetes incidence should increase by the statin administration, the benefit of the reduced risk of the cardiovascular event incidence by the statin exceeds such risk and there is no reason for stopping the statin administration. On the other hand, it has also been conceived that the statin should be used with the monitoring of the blood glucose and the glycohemoglobin blood glucose in the case of patients with borderline blood glucose and the like suffering from high risk of diabetes incidence (Non-Patent Document 3).
Some reports examine relation between the type of statin and the risk of the diabetes incidence. For example, Non-Patent Document 4 evaluated new incidence of the diabetes in aged people of at least 66 years old administered with statin, and reports that the risk of the incidence of the diabetes significantly increased in the case of atorvastatin, rosuvastatin, and simvastatin compared to the case of pravastatin, and no significant difference was found in the case of fluvastatin and lovastatin. Non-Patent Document 5 describes that, in the meta-analysis of the tolerability and safety of the statin, the risk of the incidence of the diabetes increased by the statin administration while no difference was found by the type of the statin.

Composition for reducing new-onset diabetes


Described is a remote control method of a multi-mode remote controller, comprising the following steps of: determining a current control mode, the remote controller comprising various control modes; obtaining a touch control signal of a user on a touch screen; and analyzing the touch control signal, generating a remote control instruction corresponding to the touch control signal under the current control mode, and sending the instruction to a user terminal, so that the user terminal operates currently displayed content. It is further provided a multi-mode remote controller, a user terminal and a system. Seamless automatic switching among multiple control modes in the remote controller with a touch screen can be realized, so as to meet various interaction requirements of different kinds of users.

Nowadays, televisions become increasingly more intelligent and have more functions. They are configured with intelligent operating systems, bringing more functions and experience to the users, such as picture browse, e-book reading, network browse, etc. However, a remote controller matching with the television is relatively unintelligent, it is a conventional push-button remote controller, a simulation-mouse controller, or the like. These remote controllers can only function rigidly, and a method for integrating respective control modes together and switching among the multiple control modes is desirable.

Remote control method of multi-mode remote controller, remote controller, user terminal and system

Shenzhen Skyworth Digital Technology Co., Ltd.


An assembly, preferably comprising a clearance pole, includes a first pole element with a first horizontal portion and a second vertical portion, and a second tubular pole element mounted to the ground, extending vertically, and receiving the first pole second portion. The first and second pole elements are mounted so that the first element is rotatable with respect to the second about a vertical axis. The slanted surface of an ultra-high molecular weight polyethylene block acts as a cam follower engaging a rod, bar, or tube which acts as a cam, the structures biasing the first pole element first portion to a home position. A dry lubricant is provided between the pole element bearing surfaces to provide relatively friction-free rotation between them.

Pole assemblies can be used for a wide variety of purposes, such as mounting signs on roadways (see U.S. Pat. No. 4,205,472), for traffic direction purposes (see U.S. Pat. No. 4,346,666), as a parking aid (such as shown in U.S. Pat. No. 5,231,392), or for clearance poles (such as shown in U.S. Pat. No. 5,474,016). For many of these pole assemblies it is desirable to have one pole element rotatable with respect to another pole element with a structure for biasing the elements to a home position. Usually biasing is provided by springs which may have hydraulic dampers. The return biasing means often can be more complicated than desired. Also, unless particularly low friction bearing elements are provided for allowing relative rotation between the pole elements, a poorly operating structure may be the result.
According to the present invention a pole assembly is provided which may have a wide variety of uses. The pole assembly is characterized by a secure construction which has relatively friction-free movement between elements thereof, and is versatile, being utilizable for a wide variety of purposes. However the most advantageous utilization of the pole assembly according to the invention is as a clearance pole, for example in drive-in restaurants or the like where it is necessary to provide a positive indication to vehicles having a height greater than a predetermined amount that they should proceed no further, yet damage is not done to the pole assembly. It is desirable that the pole assembly according to the invention comprise a clearance assembly having a yielding horizontal portion and a vertical support, the horizontal portion mounted above the ground a predetermined clearance height by the vertical support, the clearance height indicating the maximum height that a vehicle should have to attempt to move therepast. The construction according to the invention does not require any mounting structure above the horizontal clearance pole element. In the construction according to the invention the horizontal clearance element returns to a home position utilizing a simple, reliable, and effective structure.
According to one aspect of the present invention a pole assembly is provided comprising the following components: A first pole element having a first portion elongated in a first dimension. A second pole element elongated in a second dimension. The first and second pole elements mounted to each other so that the first dimension is substantially perpendicular to the second dimension, and so that the first pole element is rotatable with respect to the second pole element about an axis substantially coincident with the second dimension. And, a cam mounted to one of the first pole element and the second pole element. And, a cam follower mounted to the other of the first pole element and the second pole element, and engaging the cam. And, means for biasing the cam and the cam follower into engagement with each other so that upon rotation of the first pole element about the axis the cam and cam follower are maintained in engagement with each other.
The assembly may further comprise cooperating stops associated with the cam and the cam followers for stopping relative rotation of the first and second pole elements with respect to each other after a predetermined amount of relative rotation between them. The stops may be positioned so that rotation of the first and second pole elements is stopped after about 90.degree. relative rotation with respect to each other in either a clockwise or a counter-clockwise direction.
The cam and cam follower have an initial (home) position and the biasing means biases the cam and the cam follower into the initial position.
The first pole element preferably includes a second portion elongated in the second dimension, and mounted so that it is substantially concentric with a second pole element, and the biasing means preferably comprises means for stationarily mounting the second pole element so that the second dimension is substantially vertical so that gravity biases the cam and cam follower into engagement with each other, and so that the first dimension is substantially horizontal. Alternatively the biasing means may comprise a wide variety of conventional spring elements, or hydraulic or pneumatic cylinders.
Preferably a dry lubricant is provided between the second element and the second portion of the first element to provide relatively friction free rotation thereof with respect to each other. The cam follower preferably comprises a block of material having an angled face making an angle of between about 30-70.degree. with respect to the second dimension, the angled face directly engaging the cam. The cam may comprise a rod, tube or bar having an desired cross-section, but preferably being substantially circular in cross-section and extending substantially perpendicular to the second dimension and having an exterior surface. The exterior surface is engaged by the angled face. Preferably the block of material is of, or the angled face has an edge engaging the cam that is coated with, a low friction material. Preferably the block is ultra-high molecular weight polyethylene. Preferably the cam follower is stationarily mounted to the first pole element second portion, and the cam is stationarily mounted to the second pole element. The first pole element first portion is preferably positioned above the ground a predetermined clearance height indicating the maximum height that a vehicle should have to attempt to move past it.
According to another aspect of the present invention a clearance pole assembly is provided comprising the following components: A first pole element having a first, substantially horizontal, portion, and a second, substantially vertical portion. A second, tubular, pole element stationarily mounted to the ground and extending substantially vertically and receiving the first pole element second portion therein and mounting the first pole element first, substantially horizontal, portion above the ground a predetermined clearance height indicating the maximum height that a vehicle should have to attempt to move therepast. The first and second pole elements mounted so that the first element is rotatable with respect to the second element about a substantially vertical axis substantially concentric with the second pole element. And, return means for returning first and second pole elements to a home position with respect to each other, while allowing rotation of the pole elements with respect to each other from the home position, the return means comprising a cam stationarily mounted to the second pole element and a cam follower stationarily mounted to the first pole element second portion, gravity biasing the cam follower into contact with the cam.
The details of the components, and their particular construction, preferably is as set forth above.
According to yet another aspect of the present invention a clearance pole assembly is provided comprising the following components: A first pole element having a first, substantially horizontal, portion, and a second, substantially vertical, tubular portion, the first portion having clearance indicia thereon. A second, tubular, pole element stationarily mounted to the ground and extending substantially vertically and receiving the first pole element second tubular portion therein and mounting the first pole element first, substantially horizontal, portion above the ground a predetermined clearance height indicating the maximum height that a vehicle should have to attempt to move therepast. The first and second pole elements mounted so that the first element is rotatable with respect to the second element about a substantially vertical axis substantially concentric with the second pole element. A tubular extension of the first pole element first portion, extending downwardly therefrom and having a lower surface. The second, tubular, pole element having an upper surface which mates with the lower surface of the tubular extension, an interface provided between the upper and lower surfaces. A collar fixed to the tubular extension and extending downwardly therefrom and exteriorly concentric with the second pole element, the collar covering said interface. The first and second pole elements have bearing surfaces engaging each other, including distinct bearing surfaces that are vertically spaced from each other. And, a dry lubricant disposed on the bearing surfaces for facilitating low friction rotation of the first pole element second portion with respect to the second pole element about the axis.
It is the primary object of the present invention to provide a simple and effective pole assembly, desirably one that is effective as a clearance pole assembly. This and other objects of the invention will become clear from an inspection of the detailed description of the invention and from the appended claims.

Lincoln Industries Division of Progress Rail Services


A digital transmission method includes detecting a parameter of the transmission conditions, selecting a distribution of elementary coding step redundancies from a plurality of distributions of elementary coding step redundancies for which the global efficiency is equal to a target efficiency, performing a coding procedure including elementary coding steps with corresponding puncturing steps, and an interleaving step between the elementary coding steps, each of the elementary coding steps adding a redundancy by utilizing the distribution of elementary coding step redundancies, to a useful information to generate a coded information with a redundancy for a transmission, and performing a decoding procedure including elementary decoding steps, deinterleaving and depuncturing steps, and puncturing and interleaving steps corresponding to the elementary decoding steps to obtain an estimation of the useful information item.

A digital transmission system conveys information using a physical medium such as a cable, optical fiber or propagation on a radio channel and satellite. Such a physical medium will be referred to as the channel. Generally, such a system includes a channel coding device and a decoding device.
The channel coding device has an error correction coding function. The function of the error correction coding includes generating, for a useful information item, a redundant information item which, during decoding at the destination, will make it possible to reconstruct the useful information from the information arriving at its destination affected by disturbance such as the noise, attenuation and interference type occurring on the channel. A digital transmission method using such a channel coding and destination decoding is referred to as a transmission method of the error correction coding type.
The quality of a digital transmission system is evaluated, in general, by calculating the probability of error per bit transmitted. This is notably a function of the signal to noise ratio of the link. The error correction coding, associated with the corresponding decoding, aims to improve the quality of the transmission by virtue of the redundancy introduced into the signal. Redundant information having been introduced by the coding device, the decoding device will use the redundant information received and its knowledge of the coding law in order to correct any errors. In other words, at the destination, from the received information damaged by the channel, the corresponding useful information is reconstructed. For example, because of the redundancy, only certain sequences of coded information, in accordance with the coding law, are possible. If received information sequences to be decoded are different from these possible sequences, it is because they correspond to information damaged by the channel. In the case of a maximum likelihood decoding, the decoding method will reconstruct the useful information by determining, from the sequence of information received and considering the different permitted sequences, the most likely useful information sequence.
The greater the ability to discriminate between the sequences allowed by all the coding operations, the greater the error correction capability.
An important consequence of the redundancy introduced by the coding is the increase in the digital flow rate. An important parameter of the coder is therefore its efficiency, which is equal to the number of information bits per bit transmitted. In general, the lower the efficiency, the more robust the code.
The performance of a transmission with error correction coding is generally measured in terms of bit error ram or packets for a given ratio Eb/No, where Eb is the energy per information bit and No is the power spectral density of the noise. A code is deemed to be more or less efficient depending on whether its use allows a more or less low error rate for a given ratio Eb/No and for a given decoding complexity.
It is possible to improve the performance by using a code of lower efficiency. However, this is done to the detriment of the spectral efficiency of the transmission. Generally, the efficiency used is the efficiency making it possible to guarantee a predetermined error rate, this efficiency possibly being able to change according to the transmission conditions.
Known error correction codes are block codes. Block coding consists of associating, with each block of k information bits, a block of n bits (n>k) therefore containing (n−k) redundant bits. The block of n bits is obtained by multiplying the block of k useful bits by a matrix with k rows and n columns referred to as a code generating matrix. When, by permutation, the generating matrix is written in a form such that it reveals the identity matrix, so that, in the block of n bits, the k information bits and the n−k redundant bits are separated, the code is said to be systematic. The efficiency of the code is equal to k/n. The decoding device detects the errors and corrects them by means of the minimum Hamming distance. Such error defection codes which are well known in the art are for example Hamming codes, BCH codes and Reed-Solomon codes.
Effecting an error correction coding by means of one or more convolutional coders is also well known. Their operating principle consists of coding a block of k binary elements present at the input of the coder as a block of n binary elements taking account also of m blocks preceding the block at the input, by means of a register device. The output of the convolutional coder consists of n coded binary elements generated by the convolution product of the k binary elements present at the input with the response of the coder defined by n generator polynomials. The number n of generator polynomials of the coder is referred to as the dimension of the coder. The efficiency of the code is equal to k/n. The decoding device reconstructs the original data, for example by means of a decoding of the sequential type, a decoding according to the most likely symbol, or a decoding according to the most likely sequence, as described, for example, in the document "Digital Communications" by J. G. Proakis, published in 1995 by MacGraw-Hill. For example, the Viterbi algorithm provides an optimal decoding according to the most likely sequence.
According to a variant of this type of code, the coding is done not by taking directly into account a series of m useful information items preceding the information to be coded, but using a series of m auxiliary information items, stored in a device of the shin register type each obtained by the mathematical combination of a useful information item and m previously calculated auxiliary information items. Such a convolutional code is said to be recursive. When, in addition, the useful information appears as it is amongst the n outputs of the coder alongside (n−I) coded information items or redundant information items, the resulting code is referred to as a systematic recursive convolutional code, or RSC code.
Associating different coders in order to increase the performance of the coding is also known. For example, the data coded by a first coder can feed a second coder. Decoding takes place symmetrically, commencing with the second code.
A high-performance type of association of coders has been proposed, as described notably in the document "Near Shannon Limit Error-Correcting Coding and Decoding: Turbo-codes" by C. Berrou, A. Glavieux, P. Thitimajshima, which appeared in ICC-1993, Conference Proceedings, on pages 1064–1070. This type of combination of coders has given rise to a family of coding schemes known in the art as turbocodes. The term turbocodes will be applied to error correction codes based on the combination, referred to as concatenation, of several single codes, referred to as elementary codes, with the intervention of permutation operations, referred to as interleavings, which modify the order in which the data are taken into account by each of the single codes. Elementary codes means codes introducing a redundancy, of the type described above. It may be a case, for example, of systematic recursive convolutional codes for convolutional turbocodes, Hamming block or BCH codes for block turbocodes. Different types of concatenation can be envisaged. In parallel concatenation, the same information is coded by each coder separately after having been interleaved. In serial concatenation, the output of each code is coded by the following coder after having been interleaved. The dimension of the turbocode means the number of elementary coders used for implementing this turbocode. A well-known turbocoding scheme consists of a parallel concatenation of elementary codes of the Systematic Recursive Convolutional Code (RSC) type. This turbocode is referred to as PCCC. Examples of serial concatenation turbocodes arc SCCCs which use elementary codes of the convolutional code type, and block turbocodes which use elementary codes of the block code type. Serial concatenation turbocodes are described in particular in the articles "Serial concatenation of interleaved codes: Performance analysis, design and iterative decoding" written by S. Benedeno, G Montorsi, D. Divsalar and F. Pollara, in JPL TDA Prog. Rep., vol. 42–126, in August 1996 and "Analysis Design and Iterative Decoding of Double Serially Concatenated Codes with Iderleavers" written by S. Benedetto, D. Divsalar, G. Montorsi and F. Pollara, in IEEE JOURNAL ON SELECTED AREAS IN COMMUNICATIONS, vol 16, No 2, pages 231–244 in February 1998.
Information coded by a turbocode can be decoded by an iterative method referred to hereinafter as turbodecoding. In order to effect this turbodecoding, several elementary decoders with weighted inputs and outputs each corresponding to an elementary coder of the coding device are combined. The weighted inputs and outputs are effected in terms of probabilities, likelihood ratios or log likelihood ratios. Interleavers and deinterleavers enable each decoder to take into account an item of information which is presented in the same order as a corresponding item of information at the output or input of the corresponding coder. Each elementary decoder receive an item of information corresponding to an item of information output from the corresponding coder and an item of information corresponding to input information of the corresponding coder, and generate information of increased reliability. The supplementary information generated by an elementary decoder is referred to as the extrinsic information. It is used by one or more other elementary decoders after adapted interleaving or deinterleaving. The exchange of extrinsic information takes place between elementary decoders within the same step, and from this step to the following step. Each new step therefore increases the reliability of the information generated at the output. The elementary decoders use for example MAP, LogMAP, MaxLogMAP, SOYA, or Chase algorithms which are described, for example, in the articles "Optimal and sub-optimal maximum a posteriori algorithms suitable for turbo decoding" by P. Robertson, P. Hoeher and E. Villebrun, which appeared in European Trans. on Telecommun., vol. 8, March-April 1997, on pages 119–125 and "A very low complexity block turbo decoder for product codes" by R. Pyndiah, P. Combelles and P. Adde, which appeared in Proc. IEEE Globecom 1996, on pages 101–105. A thresholding is applied to the information output from the last decoding step in order to generate the decoded information.
The term turbodecoding encompasses various concatenation schemes which can be envisaged, dependent for example on the type of turbocoding used. For example, in a turbodecoding corresponding to a serial concatenation turbocode, the elementary decoders being associated in reverse order of the elementary coders, each elementary decoder receives two priori weighted information items corresponding one to the output information from the corresponding elementary coder and the other to the input information of the corresponding elementary coder. This elementary decoder produces two posterior weighted information items, one corresponding to the output of the corresponding elementary coder and which therefore becomes, during a following iteration, after corresponding interleaving, the priori input of a preceding elementary decoder, and the other corresponding to the input of the corresponding elementary coder, and which therefore becomes, in the same iteration, after corresponding deinterleaving, the priori input of a following elementary decoder. Examples of turbodecoding for serial concatenation turbocodes are described notably in the aforementioned articles "Serial concatenation of interleaved codes: Performance analysis, design and iterative decoding" written by S. Benedetto, G Montorsi, D. Divsalar and F. Pollara, in JPL TDA Prog. Rep., vol. 42–126, in August 1996 and "Analysis Design and Iterative Decoding of Double Serially Concatenated Codes with Interleavers" written by S. Benedetto, D. Divsalar, G. Montorsi and F. Pollara, in IEEE JOURNAL ON SELECTED AREAS IN COMMUNICATIONS, vol 16, No 2, pages 231–244 in February 1998. The elementary decoders are in general concatenated in series, but other types of concatenation may be envisaged.
Whatever the case, the extrinsic information can always be defined as the additional information afforded by an elementary decoding associated with an elementary coding with respect to a priori information item, acting at the input of the elementary decoding.
It is also known that the efficiency of a code can be increased by a puncturing operation, which consists of not transmitting certain bits in a sequence of information, as described, for example, in the article "Rate-Compatible Punctured Convolutional (RCPC) codes and their application" by J. Hagenauer, which appeared in IEEE Trans., Vol COM-36.4, 1988, on pages 389–400 or in the article "New Rate Compatible Punctured Convolutional Codes for Viterbi Decoding" by L. H. C. Lee, which appeared in IEEE Trans., Vol. COM-42.2, 1994, on pages 3073–3079. These non-transmitted bits are in general redundant information bits. One or more puncturing operations occur at transmission, after one or more coding operations. At the destination, one or more reciprocal depuncturing operations are carried out before one or more decoding operations. The puncturing of redundant information bits reduces the correction capacity of a code and increases its efficiency.
In the case of serial concatenation turbocodes, the puncturing, on transmission, can occur after each elementary coding operation, before the interleaving operation. There will generally be, in the case of serial concatenation turbocodes, as many puncturing matrices as there are elementary coders. The efficiency of the elementary codes not generally being the same and the puncturing being generally distributed unequally, the size of a given interleaves will depend on the one hand on the efficiency of the elementary code which precedes it and on the other hand on the puncturing matrix interposed between this elementary code and this interleaves. The global efficiency of the serial turbocode will be equal to the product of the efficiencies of the elementary codes each modified by the corresponding puncturing.
The error correction codes of the family of turbocodes according to the state of the art described above make it possible to obtain very high performance error correction whilst preserving sufficiently high efficiency and allowing decoding operations of low complexity compared with the complexity of the code.
However, it is known that the performance of a transmission using an error correction code varies according to the transmission conditions. Transmission conditions means the parameters having an influence on the performance of the transmission such as in particular the signal to noise ratio, but also the bit or packet error rate, the signal to interference plus noise ratio, the number of active users of a telecommunications system, the quality of service required by the transmission system, the speed of movement of the user of the transmission system or any other parameter.
In the state of the adaptation to the transmission conditions is effected by decreasing or increasing the efficiency in order to make the code more or less robust depending on whether the channel is more or less harsh.
One object of the present invention is to allow a dynamic adaptation to the transmission conditions of an error correction code transmission method of the serial concatenation turbocode type, at constant efficiency.


A lid and closure member assembly for placement on a container is provided. The lid includes a cover portion, an access port and an elongated channel defined in the cover portion. The channel may include two opposing side walls, two opposing end walls and a bottom. The channel's side walls can each include an inwardly-projecting lip forming an undercut for slidably receiving a portion of the closure member. The closure member includes an access port cap, a retainer slidably received within the channel and a strap extending between the access port cap and the retainer. The closure member is selectively movable between open and closed positions. The access port cap may cover the access port when the retainer is in a first position within the channel or may be at least partially received within the channel when the retainer is in a second position within the channel.

It is very common in today's society for consumers to obtain beverages, such as coffee, tea, a soft drink, milk or juice, from fast food restaurants and convenience stores in relatively large quantities. These beverages are placed into large cups and are generally not consumed entirely in a single sitting. Rather, it is common for such beverages to be consumed over a duration of time. Often, such beverages are obtained while traveling and will be consumed in a car. Thus, it is desirable these beverages to be covered for a number of reasons, including preventing spillage.
Cups and cuplike containers beverages are often provided with lids to cover the contents before and during use. Such lids normally snap over the open end of the cup and are disposable after use. Consumers often prefer to access the contents within the cup with minimal disruption to the lid. Therefore, such lids often include openable access closures. Such access closures often include a perforated tab near the peripheral region of the lid that may be hinged back or removed entirely to provide access to the contents within the container. Such lids require that the apron of the lid, which defines its periphery, be torn back to reveal the opening. Once the periphery of the lid is broken, its engagement to the cup is much less secure. Additionally, once torn away and folded back, such tabs generally do not adequately seal the opening in order to prevent spillage when the cup is incidentally tipped or jarred.
It is also desirable for the user to have intermittent access to the beverage, which can involve the opening and closing of the lid or a portion thereof. Because the quantity of beverage may be consumed over a duration of time, it is further desirable to have a re-closable lid having a closure mechanism that will not become detached therefrom and misplaced while a part of the beverage remains in the container.
Thus, a need exists for a lid having a closure member that may be opened without requiring the lid's periphery to be broken. A need also exists for a lid and closure member assembly adapted for providing convenient access to the contents within the cup. Finally, a need exists for a lid having a closure member attached thereto such that the closure member will not become removed or misplaced over a period of time.


Nucleic acid based methods for detecting the presence of E. coli or Shigella or related microorganisms in a sample using one or more E. coli or Shigella species specific nucleotide sequences are disclosed. More particularly the identification of molecules capable of binding or otherwise facilitating abnormal cell growth or abnormal physiology such as found in cancer or cellular instability is described. Further, molecular probes for performing the nucleic-acid based methods and methods of testing and selecting nucleic acid sequences suitable for same are provided. The methods and polynucleotides are useful inter alia in the testing of food and water samples, for testing for genetic and cellular instability, and for testing benign, pre-neoplastic and neoplastic disease in asymptomatic or symptomatic colorectal or gastric cancer patients or those at risk of the aforementioned conditions or those infected by Escherichieae and with other diseases or conditions.

The identification of bacteria can be carried out using biochemical, cultural, antibody recognition and molecular biological tests (Feng P C S and Hartman P A: Fluorogenic Assays for Immediate Confirmation of Escherichia coli. 1982. Falkow S, Habermehl K O. ed: Rapid Methods and Automation in Microbiology and Immunology. Springer-Verlag, Berlin 1985: 30–33. AOAC Official Methods of Analysis 1995. Pepper Ill., Gerba C P and Brendecke J W: Environmental Microbiology. A laboratory Manual. Academic Press 1995.)
Food and Water Hygiene
Biochemical Test and Culture Medium
The most probable number (MPN) is the common method for the detection and quantitation of E. coli in foods. This method detects E. coli on the basis of the bacteria's ability to ferment lactose with the evolution of gas. Other non-E. coli organisms also ferment lactose and, therefore, several selective enrichment steps are required in order to sequentially select for coliform bacteria and E. coli.
This widely used MPN method has several limitations. Many clinical E. coli isolates are lactose negative and thus are not detected using the MPN method. The MPN method requires a minimum of about four days to determine the absence of E. coli in food products and about seven days are required to get confirmed results. The growth of some E. coli, including the serotype 0157:H7 strains, is severely inhibited by the selectivity of the EC broth at 45.5° C. and gas production in the MPN method is susceptible to interference by high levels of competitor organisms.
More rapid methods for detecting E. coli are needed because of the time and accuracy limitations of the MPN method. It has been reported that 94% to 97% of E. coli strains possess the B-D-glucuronidase that can be detected by specific hydrolysis of a synthetic substrate, 4-methylumbelliferyl-B-D-glucuronide (MUG), to a fluorescent end product. When MUG is incorporated into lauryl sulfate tryptose (LST) broth, 107 to 108 CFU/ml of E. coli will yield this fluorescent product which can be detected under longwave UV light. However, a number of enteropathogenic E. coli including serotype 0157:H7 strains, do not possess the B-D-glucuronidase enzyme, do not exhibit fluorescence in LST-MUG medium, and therefore yield false-negative results using the MUG method. In addition, the selectivity of the method is compromised by the fact that some Shigella, Citrobacter, Ecterobacter, Klebsiella, Salmonella, and Yersinia species also produce B-D-glucuronidase and therefore yield false-positive results.
Another widely used test, the Analytical profile index (API) test strips, produced by BioMerieux (France), may be used to obtain test results quickly. These consist of a series of miniature capsules on molded plastic strips, each of which contains a sterile dehydrated medium in powder form. Addition of water containing a bacterial suspension simultaneously re-hydrates and inoculates the medium. A rapid reaction is obtained because of the small volume of medium and the large inoculum used. The identification of the unknown bacterium is achieved by determining a seven digit profile index number and consulting the API profile recognition system. However, there are strains of E. coli that yield a low discrimination value with the API strips.
When this occurs, further identification with sugar test is required for affirmation. Acid production from sugars such as D-Adonitol, Cellobiose, Lactose and D-Xylose are additional biochemical test for differentiation of Escherichia species and related species.
DNA Probes
The use of genetic probes in the detection of microorganisms is popular because they obviate the need for pure cultures, and are specific, sensitive, fast and reliable (Fred C. Tenover: DNA probes for infectious diseases. CRC Press, Inc. 1989). In DNA probe test, it is essential to know something about the nucleotide sequence of the microorganisms under investigation.
Bacteria belonging to different families or strains can be differentiated on the basis of heterogeneity in genetic sequences. One approach is the identification and use of specific toxin genes of disease causing strains to distinguish them from the normal flora. Another approach makes use of the conserved and polymorphic sites that are found in bacterial 16S ribosomal RNA (rRNA) sequences not present in human 18 rRNA or human mitochondrial 12S rRNA. The combination of the polymerase chain reaction technique for gene amplification, followed by sequencing of polymorphic regions and phylogenetic analysis of the resulting sequence information can also assist in strain identification. (Relman et al. The New Engl J of Medicine, 327: 293–301, 1992, Kui et al. FEMS Microbiology Letters 57:19–24, 1989. DeLong et al. Science 243: 1360–1363, 1989).
The E. coli identification kit produced by gene-trak systems, Framingham, Mass., USA, uses DNA oligonucleotides that complement the 16S rRNA. This assay uses hybridization techniques to detect E. coli, non-coli Escherichia fergusonii and Shigella species.
Another way of identifying bacteria specific DNA probes is by using randomly cloned chromosomal fragments. This involves the cloning of restriction enzyme cleaved genomic DNA of a bacteria, and selection of specific clones by determining their hybridization profiles by hybridization against its own species-sequences and other species-sequences. Only clones that hybridize to sequences from the same species but the clones were derived from will be selected (Tenover FC: DNA Probes for Infectious Diseases. CRC Press 1989).
Gastrointestinal Infection
Colorectal cancer is one of the top three cancer killers in the world. Factors implicated in its etiology include inappropriate diet, environmental factors and lack of reliable diagnostic markers. Recently, greater understanding of the genetic predisposition to colon cancer has been achieved through the identification of genes responsible for such susceptibility (Cowell J K, ed: In Molecular Genetics of Cancer. Dunlop M G: Molecular genetics of colon cancer. 1995. 113–134). Despite intensive research efforts, the mortality rate from colorectal cancer has not declined dramatically over the last 40 years.
Markers associated with cancer initiation or progression are important in patient care. Tumours diagnosed at an early stage can usually be cured by surgical excision or polypectomy (surgical excision cures 90% of patients with adenoma or carcinomas that are confined to the mucosa). Patients with advanced disease have a poor prognosis as mortality increases to more than 90% after metastasis takes place.
The gastrointestinal tract is often exposed to a range of microorganisms. When bacteria come into contact with a susceptible host, they can establish either a transient presence, colonize the individual, infect the individual or evolve with the host. The outcome can either be harmless, acute illness or a chronic condition that may lead to a serious outcome (Gibson G R and Macfarlane G T: Human Colonic Bacteria: Role in Nutrition, Physiology, and Pathology. CRC Press, Inc., 1995).
Bacteria have been associated with inflammatory bowel disease such as ulcerative colitis and Crohn's disease (Giaffer et al. Gut 33:646–650, 1992, Cartun et al. Mod Pathol 6:212–219, 1993; Liu et al. Gastroenterology 108:1396–404, 1995). In addition, patients with pan-colitis of long duration are at risk of developing colorectal cancer (Wanebo H J: In Colorectal Cancer. Lev R: Precursors of Colon Carcinoma 1993; 158–163). Although frequently implicated, the role of bacteria in colon related disease remains ill-defined and controversial. The identification of bacteria in physical proximity to diseased tissue does not provide definitive proof of a causal relationship between a bacterium and the diseased condition. This is especially so when the bacteria are commonly found surrounding the tissue (Swidsinski et al. Gastroenterology 115:281–286, 1998), as is the case in the colon, and there is no additional information to differentiate between bacteria. It is perhaps more convincing if the bacterium can be shown to be positioned in-situ in the diseased tissue and when isolated and characterized found to possess properties that will substantiate its presence within the tissue.
The bacterium Helicobacter pylori is an accepted Group 1 (definite) biological carcinogen for gastric cancer and causes of related gastric conditions such as duodenal ulcer, gastric ulcer and ulcer complications. H. pylori attaches to and thrives on the gastric mucosa resulting in a chronic immunological response from the host. (Marshall, B. J. Gastroenterologist 1:241–247, 1993). It is not firmly established whether H. pylori has invasive properties. However, pathogenic strains have been identified that can cause epithelial cell damage and mucosal ulceration on an intragastric administration to mice (Telford et al. J Exp Med 179:1653–1658, 1994) The question remains whether H. pylori is the only important factor in the development of gastric cancer because of its high infection/disease ratio. The current consensus is that there may be other factors other than H. pylori infection that are also important in gastric cancer risk (National Institutes of Health Consensus Development Panel on Helicobacter pylori in Peptic Ulcer Disease 1994). A separate study put forward the theory that a synergistic interaction between a non-invasive bacteria and other enteropathogens can facilitate invasion by the otherwise non-invasive bacteria (Geir Bukhowm and Georg Kapperud, Infection and Immunity 55:2816–2821, 1987).
Numerous in-vivo and in-vitro studies have vividly shown that microorganism carry transmissible tumorigenic genetic information. Mutagenesis in such instances is either by transposition or site-specific recombination facilitated by conjugation, transformation and transduction. This information is constantly being exploited scientifically in creating mutants (Sherratt D J (ed): Mobile genetic elements. Dale J W: Molecular genetics of bacteria. 2nd Edition. John Wiley and Sons Ltd. Oxford University Press 1995). In 1995, Couralin et al. showed that invasive strains of Shigella flexneri and E. coli can carry out gene transfer that are stably inherited and expressed by the mammalian cell progeny (Courralin et al., C. R. Acad. Sci. Paris 318:1207–1212, 1995). Therefore, it is quite possible that the persistent presence of bacterial genetic sequences in the nucleus of mammalian cells can lead to genetic instability that may ultimately give rise to a tumour cell.
Bacterial invasion can stimulate similar a pattern of protein phosphorylation to that induced by growth factor (e.g. EGF) and cellular proliferative responses may then be altered with consequences for disease progression. (Galan et al. Nature 357:588–589, 1992). In addition, bacterial disruption of cell-cell interaction may affect cell proliferation patterns and differentiation (Epenetos A A and Pignatelli M (ed): Cell Adhesion Molecules in Cancer and Inflammation; Pignatelli et al.: Adhesion molecules in neoplasia: An overview. Chapter 1:1–13. Harwood academic publishers 1995). Cytonecrotizing factors have been identified that can cause formation of large multinucleated cells and cells spreading in tissue cultures. (Denko et al. Experimental Cell Research 234:132–138, 1997; Lemichez et al., Molec Microbiol 24:1061–1070, 1997; Machesky, L. M. and Hall, A, TICB 6:304–310, 1996). Accordingly, the persistence presence of bacteria can cause cellular changes leading to cell disorientation, proliferation and changes in cell morphology.
One cancer causing effect of bacteria is when Agrobacterium tumefaciens, a soil phytopathogen, genetically transforms plant cells by the transfer of the tumour-inducing (Ti) plasmid to the plant genome where its integration and expression result in the crown gall phenotype. A crown gall is a tumorous proliferation of plant cells which are released from normal metabolic and reproductive controls (Hughes M A: Plant Molecular Genetics. Addison Wesley Longman Ltd. 1996).
People travelling across continents may suffer from traveler's diarrhoea as the bacteria they are exposed to are not common in their county. The assays/kits that are used for detecting microorganisms in the Asia-Pacific region are imported from other continents and these imported assays/kits may not be as sensitive or as specific for the bacteria in the Asia-Pacific region.
Microorganisms transmitted by water and food usually grow in the intestinal tract of man and animals and leave the body in the faeces. Bacteria are known to possess gene sequences that make them toxigenic, hemorrhagic, invasive and adherent to tissues. Acute bacterial infection is well documented but it is still not known that if bacteria that do not cause overt symptoms but persist and remain undetected in their host can cause diseases with time. Therefore, it is important that the assays that are available are sensitive and specific for a wide range of pathogens.
The E. coli genetic sequence is published. (Blattner et al. Science 277:1453–1474, 1997). Some of its genetic sequence has homology to other bacteria (Janda J M and Abbott S L: The Enterobacteria. Lippincott-Raven Press 1998). The inventor, in accordance with the present invention, has identified E. coli DNA sequences which are unique to the Escherichae family and furthermore has shown that biochemical and cultural tests presently available are not adequate for detecting this family of bacteria. The present polynucleotide sequence in the genome of strains of the Escherichieae genus (Escherichia and Shigella), have proven to be more informative than the agar plates EMB, MacConkey and MUG. They can be used to detect E. coli that is either EMB, MacConkey or MUG negative. The sequences are also found in 0157:H7 and 029:NM strains of E. coli. Therefore, the present molecular markers provide improved tools for the detection and characterization of E. coli.
In addition, the invention permits the use of the sequence(s) to study the outcome of tissue infection in-situ. The present gene sequences are more specific than the gene-trak sequence (gene-trak systems) and the sequences can be amplified many-fold to increase their detection limit. This makes the present invention useful for studying the role of microorganism in gastrointestinal and other disease conditions. The presence of the polynucleotide sequence in cells can be located by the use of the polymerase-chain-reaction amplification technique in-situ followed by hybridization to the in-situ amplified signals with sequence specific DNA probe.
The identification of these specific polynucleotide sequence(s) that can be used to detect for the presence of strains of E. coli and Shigella and related microorganisms in food, water, fecal specimens, tissues, secretions and other biological, environmental and/or laboratory samples is important for health reasons as it enables one to check on the quality of food and water hygiene and monitor transmission of the microorganism. Sensitive detection techniques and methods for assessing the role of bacteria in clinical conditions will ultimately help in the control of harmful microorganisms.