An adhesive patch is provided wherein the patch includes a flexible backing having a front side and a back side. The patch also includes a therapeutic formulation positioned on and in at least a portion of the front side of the backing such that the therapeutic formulation is partially embedded in at least a portion of the front side of the backing. At least a portion of the backing is treated with a hydrophobic sizing agent such that the portion of the backing that is treated with the hydrophobic sizing agent has a surface energy of about 20 dynes/cm2 to about 65 dynes/cm2. The therapeutic formulation includes a topical acne drug, a solvent that dissolves the topical acne drug, and a pressure sensitive adhesive.

Acne vulgaris is a chronic disorder of the pilosebaceous follicles (apparatus) characterized by comedones (blackheads), papules, pustules, cysts, nodules, and often scars, that appear on the most visible areas of the skin (e.g., the face, chest, back, neck, and upper arms). The pilosebaceous apparatus is largely under the control of endogenous hormones (mainly androgens) which are present in unusually high concentrations in the blood during adolescence and puberty, giving rise to an excessive production of sebum. The condition may worsen by a simultaneous increase in the rate of keratinization of the skin""s horny layer (the stratum comeum). As the horny cells proliferate, they can form an occlusive plug or comedone which coupled with the increased production of the sebum, represents an ideal medium for the proliferation of the skin resident strains, such as the Gram positive anaerobic bacterium, Propionibacterium acnes. Eventually, the plugged follicles rupture and allow the discharge of their contents, causing local swelling and inflammation. The exposed follicles may darken from the deposition of pigment from damaged cells in the deeper layer of skin. In severe cases, acne can lead to hospitalization of the patient, extensive discomfort, and long term scarring of the skin.
There are numerous treatments available for treating acne. Typically, acne is treated with topical formulations in the form of creams, gels, emulsions or lotions that contain selected agents. These agents include hormones or hormone agonists and antagonists (EP A1 0 563 813 and U.S. Pat. No. 5,439,923), antimicrobial agents (U.S. Pat. No. 4,446,145, GB 2,088,717, GB 2,090,135, GB 1,054,124, U.S. Pat. No. 5,409,917), salicylic acid (U.S. Pat. No. 4,514,385, U.S. Pat. No. 4,355,028, EP A1 0 052 705, FR-A 2,581,542, and FR-A 2,607,498). The problems associated with topical treatment of acne with creams, gels, emulsions and lotions include, e.g., the lack of precision of the application of the cream, gel, emulsion or lotions and the associated lack of control over precise doses to the target site. The application of a cream, gel, emulsion or lotion typically results in the exposure of an area considerably in excess of that covered by the acne, thereby exposing normal healthy skin to the anti-acne formulation. In addition, creams, gels, emulsions and lotions are messy and inconvenient.
Oral administration of anti-acne agents is currently provided for severe cases of acne. These are reviewed in xe2x80x9cAcne, A Review of Optimum Treatmentxe2x80x9d by Sykes N. I. and Webster G. F in Drugs 48, 59-70 (1994). Numerous side-effects have been described using oral administration of anti-acne drugs. For example, isotretinoin, which is a derivative of vitamin A has associated risks of teratogenicity and may be a risk for women of childbearing age. Oral administration of antibiotics suited for treating acne may induce the appearance of adverse effects which include abdominal cramps, black tongue, cough, diarrhea, fatigue, irritation of the mouth and other undesirable symptoms.
Salicylic acid in the form of a tacky hydrophilic gel dressing (U.S. Pat. No. 5,258,421) and in combination with pantothenic acid or pantothenic acid derivative in a cleansing pad (PCT WO 93/21899) has been used for treating acne. In addition, a patch containing cephalosporin has been described in U.S. Pat. No. 5,409,917 for the treatment of acne using a method for making nicotine patches. Since the patch was not optimized for the special circumstances associated with acne including optimizing the anti-acne agent content and placement of the patch at multiple locations on exposed skin such as the face, the patch has not been adopted as an anti-acne formulation delivery modality.
FDA regulations (e.g., 21 C.F.R. Chapter 1, Section 333, Subpart D-Topical Acne Drug Products, Apr. 1, 2000 Edition) regulate what components (i.e., xe2x80x9cactive ingredientsxe2x80x9d), in a specified amount, may be described as treating acne (i.e., contains a topical acne drug). In order to follow FDA regulations, therefore, only a select number of active ingredients that are able to treat acne, in a specified amount, may be included in an adhesive patch when the patch is described as treating acne. Consequently, it is difficult to manufacture an adhesive patch that includes a topical acne drug, while at the same time maintaining (a) the solubility and stability of the active ingredients in the therapeutic formulation, (b) the pressure sensitive adhesive properties of the therapeutic formulation, and (c) following FDA regulations.
Several adhesive patches, drug dispensing devices, electrodes, and bandages have been disclosed for applying salicylic acid and/or sulfur to skin. See, e.g., U.S. Pat. Nos. 6,096,334; 6,096,033; 5,741,510; 5,536,263; 4,675,009; 4,307,717; and 4,274,420; which are all commonly assigned to Lec Tec Corporation. U.S. Pat. No. 4,274,420 discloses an electrode for use in monitoring and stimulation medical applications. The electrode includes a connector plug and a skin-interfacing substrate material. The substrate material can include salicylic acid in 17.8 wt. % (see, Example 2). The reference, however, does not disclose or suggest that the electrode can be used to treat acne. In addition, the reference does not disclose or suggest that salicylic acid can be present in the amount permitted by the FDA (e.g., 0.5 wt. % to 2.0 wt. % of the substrate). As such, the amount of salicylic acid disclosed therein does not comply with FDA regulations for topical acne drugs. See, 21 C.F.R. Chapter 1, Section 333, Subpart D- Topical Acne Drug Products, Apr. 1, 2000 Edition. Additionally, the backing is not disclosed as being treated with a sizing agent.
U.S. Pat. No. 4,307,717 discloses a bandage that includes a backing element and a substrate attached to the backing element. The substrate includes a matrix that includes a medicament. It is disclosed that the medicament can be a keratolytic agent such as salicylic acid or an antipruritic agent such as sulfur. However, the amount of salicylic acid or sulfur that can be employed in the matrix or substrate is not disclosed. The reference does not disclose or suggest that the bandage can be used to treat acne. In addition, the reference does not disclose or suggest that salicylic acid or sulfur can be present in the amount permitted by the FDA (e.g., 0.5 wt. % to 2.0 wt. % of the substrate or 3.0 wt. % to about 10.0 wt. % of the substrate, respectively). See, 21 C.F.R. Chapter 1, Section 333, Subpart D- Topical Acne Drug Products, Apr. 1, 2000 Edition. Additionally, the backing is not disclosed as being treated with a sizing agent.
U.S. Pat. No. 4,675,009 discloses a drug dispensing device (e.g., an adhesive skin reservoir) for the transdermal delivery of a medicament. The drug dispensing device includes a backing element and a substrate attached to the backing element. The substrate includes a medicament wherein the medicament can be a keratolytic agent such as salicylic acid (see, col. 3, line 66) or an antipruritic agent such as sulfur. The salicylic acid can be present in 8-20% of the substrate (see, Example 20). The amount of sulfur that can be employed in the substrate is not disclosed. The reference does not disclose or suggest that the drug dispensing device can be used to treat acne. In addition, the reference does not disclose or suggest that salicylic acid or sulfur can be present in the amount permitted by the FDA (e.g., 0.5 wt. % to 2.0 wt. % of the substrate or 3.0 wt. % to about 10.0 wt. % of the substrate, respectively). See, 21 C.F.R. Chapter 1, Section 333, Subpart D- Topical Acne Drug Products, Apr. 1, 2000 Edition. Additionally, the backing is not disclosed as being treated with a sizing agent.
U.S. Pat. Nos. 5,536,263 and 5,741,510 disclose an adhesive patch for applying medication to the skin. The patch includes a backing and a hydrocolloidal gel located on and in the backing. The gel includes a pressure-sensitive adhesive and a medicament. The medicament can be a keratolytic agent such as salicylic acid (see, col. 5, lines 35-36). The salicylic acid can be present in 4.1 wt. % (see, Example 46). The reference does not disclose or suggest that the adhesive patch can be used to treat acne. In addition, the reference does not disclose or suggest that salicylic acid can be present in the amount permitted by the FDA (e.g., 0.5 wt. % to 2.0 wt. % of the substrate). As such, the amount of salicylic acid disclosed therein does not comply with FDA regulations for topical acne drugs. See, 21 C.F.R. Chapter 1, Section 333, Subpart D- Topical Acne Drug Products, Apr. 1, 2000 Edition. Additionally, the backing is not disclosed as being treated with a sizing agent.
U.S. Pat. Nos. 6,096,333 and 6,096,334 disclose adhesive patches for applying medication to the skin. The patch includes a backing layer and a hydrophilic pressure-sensitive adhesive reservoir that includes a medicament. The medicament can be a keratolytic agent such as salicylic acid (see, col. 5, line 41). The salicylic acid can be present in 4.1 wt. % (see, Example 46). The references do not disclose or suggest that the adhesive patches can be used to treat acne. In addition, the references do not disclose or suggest that salicylic acid can be present in the amount permitted by the FDA (e.g., 0.5 wt. % to 2.0 wt. % of the substrate). As such, the amount of salicylic acid disclosed therein does not comply with FDA regulations for topical acne drugs. See, 21 C.F.R. Chapter 1, Section 333, Subpart D- Topical Acne Drug Products, Apr. 1, 2000 Edition. Additionally, the backing is not disclosed as being treated with a sizing agent.
The adhesive patches, drug dispensing devices, electrodes, and bandages disclosed in, e.g., U.S. Pat. Nos. 6,096,334; 6,096,033; 5,741,510; 5,536,263; 4,675,009; 4,307,717; and 4,274,420 have experienced success in applying and/or delivering medication to the skin. There exist several drawbacks, however, in the use of these adhesive patches, drug dispensing devices, electrodes, and bandages for delivering salicylic acid, in the amount permitted by the FDA, to treat acne or pimples. Specifically, the use of salicylic acid permitted by the FDA for acne medications has resulted in a less than desirable overall yield of product, a less than desirable xe2x80x9choldoutxe2x80x9d of therapeutic formulation on the backing, and a more than desirable degree of penetration of the therapeutic formulation in the backing.
U.S. Pat. No. 5,976,565 discloses a device for the topical treatment of acne. The device requires the presence of at least two agents suited for treating acne. See, e.g., col. 2, lines 36-37. The patch disclosed therein includes a release layer and at least one adhesive polymeric matrix layer located between the backing film and the release layer. As such, the adhesive polymeric matrix layer is not disclosed as being embedded or partially embedded in the backing film.
Many adhesive patches are manufactured or produced, for example, by mixing an ointment or gel in a mixer, then expelling the ointment or gel in a fluid state from the mixer onto the exposed front surface of a backing sheet. The fluid ointment or gel is then spread over the exposed surface of the backing sheet using an appropriate direct coating technique, such as knife-over-roll. This method of application allows the ointment or gel to penetrate a substantial portion of the backing sheet before it solidifies. However, if the fluid ointment or gel penetrates the backing too rapidly, it is possible for the ointment or gel to penetrate through the entire thickness of the backing before solidifying. Complete penetration of the ointment or gel through the backing results in the back side of the backing having a tacky surface. A tacky back side of the backing is unacceptable in that it may cause problems with further processing, such as die cutting or packaging, that is required to produce a finished product, and because it is an unattractive feature to the product consumer. Controlling the rate of penetration, such that the gel or ointment has solidified after it has begun to penetrate the backing, but before it has passed completely through the backing, or controlling the depth to which the ointment or gel will easily penetrate before solidifying, has been a persistent challenge.
There is a need therefore for methods and devices for treating patients with acne that have minimum adverse effects, have maximum efficacy, may be simple and comfortable to use, administers to the skin an effective and known amount of a topical acne drug, and complies with FDA regulations. The device will preferably be an adhesive patch that effectively controls the rate of penetration and/or effectively controls the depth to which the ointment or gel will penetrate before solidifying.
The present invention provides a water insoluble, protective, adhesive patch useful for treating or preventing acne or a pimple. The patch can prevent infections associated with acne or a pimple. The patch administers to the skin an effective and known amount of a topical acne drug. The patch maintains the adhesiveness of the adhesive and the stability of the topical acne drug over a prolonged period of time typically experienced in the manufacturing, packaging, shipping, and/or the storage of the patch. The topical acne drug, solvent, and pressure sensitive adhesive are positioned on at least a portion of the adhesive patch, in at least a portion of the adhesive patch, or on and in at least a portion of the adhesive patch. Preferably, the topical acne drug, solvent, and pressure sensitive adhesive are partially embedded in at least a portion of the adhesive patch. Additionally, the patch complies with FDA regulations (e.g., 21 C.F.R. Chapter 1, Section 333, Subpart D- Topical Acne Drug Products, Apr. 1, 2000 Edition). The adhesive patch of the present invention can include a gel that is not water-based. The adhesive patch includes a backing that is treated with a hydrophobic sizing agent (e.g., a fluorocarbon solution, silicone, or a combination thereof). The use of such backing prevents immediate wick through and maintains the hydrogel from penetrating the backing too quickly. In addition, the use of such backing provides a patch with a higher yield improvement and superior holdout properties. The use of such backing also obviates the need for a backing liner or a release liner. In such an embodiment, the adhesive patch can exist as a self wound adhesive patch.
The present invention provides an adhesive patch. The adhesive patch includes a flexible backing having a front side and a back side. A therapeutic formulation is positioned on at least a portion of the front side of the backing, in at least a portion of the front side of the backing, or on and in at least a portion of the front side of the backing. At least a portion of the backing is treated with a hydrophobic sizing agent such that the portion of the backing that is treated with the hydrophobic sizing agent has a surface energy of about 20 dynes/cm2 to about 65 dynes/cm2. The therapeutic formulation includes a topical acne drug, a solvent that dissolves the topical acne drug, and a pressure sensitive adhesive.
The present invention also provides for another adhesive patch. The adhesive patch includes a flexible backing having a front side and a back side. A therapeutic formulation is positioned on at least a portion of the front side of the backing, in at least a portion of the front side of the backing, or on and in at least a portion of the front side of the backing. At least a portion of the backing is treated with a hydrophobic sizing agent such that the portion of the backing treated with the hydrophobic sizing agent has a surface energy of about 20 dynes/cm2 to about 65 dynes/cm2. The therapeutic formulation includes salicylic acid or a pharmaceutically acceptable salt thereof present in about 0.5 wt. % to about 2.0 wt. % of the therapeutic formulation, a solvent that dissolves the salicylic acid, and a pressure sensitive adhesive.
The present invention also provides another adhesive patch. The adhesive patch includes a flexible backing having a front side and a back side. A therapeutic formulation is positioned on at least a portion of the front side of the backing, in at least a portion of the front side of the backing, or on and in at least a portion of the front side of the backing. At least a portion of the backing is treated with a hydrophobic sizing agent such that the portion of the backing treated with the hydrophobic sizing agent has a surface energy of about 20 dynes/cm2 to about 65 dynes/cm2. The therapeutic formulation includes a topical acne drug and a hot melt adhesive.
The therapeutic formulation can be partially embedded in at least a portion of the front side of the backing. The therapeutic formulation can be located on the entire surface of the front side of the backing. The backing can be porous. The backing can be vapor permeable. Upon contact with skin, the backing can retain the therapeutic formulation while the patch allows moisture from the skin to pass. The backing can include water insoluble material. The backing can have a thickness of about 0.025 mm to about 1.25 mm. The backing can include a nonwoven fabric. The backing can include polycellulose fibers, polyester fibers, polyurethane fibers, polyolefin fibers, polyamide fibers, cotton fibers, copolyester fibers, or any mixture thereof.
The hydrophobic sizing agent can be a fluorocarbon solution, a silicone-containing compound, or a combination thereof. The backing that is treated with the fluorocarbon solution can be Vilmed M1585 W/HY, Vilmed M1585H/HY, Vilmed M1586 W/HY, Vilmed M1586 H/HY, Vilmed M1570, Vilmed M 1573 F, Vilmed M 1573 FH, Vilmed M 1577 F, Vilmed M 1578 F, Vilmed M 1578 FH, or a combination thereof. The silicone-containing compound can be a polydimethyl siloxane, a dialkylsiloxane, a dimethylsiloxo vinyl alkene, a dialkylsiloxo vinyl alkene, a dimethylsiloxo acrylate, a dialkylsiloxo acrylate, a vinyl terminated polydimethylsiloxane, a vinyl terminated polydialkylsiloxane, or a combination thereof. At least a portion of the front side of the backing treated with the sizing agent. The entire surface of the front side of the backing can be treated with the sizing agent. The entire backing can be treated with the sizing agent. The sizing agent can be partially embedded in the backing.
The topical acne drug can be salicylic acid, resorcinol, resorcinol acetate, benzoyl peroxide, sulfur, retinol, retinoic acid, citric acid, an alpha hydroxy acid, retinal, a pharmaceutically acceptable salt thereof, or any combination thereof. The topical acne drug can be salicylic acid or a pharmaceutically acceptable salt thereof. The salicylic acid or the pharmaceutically acceptable salt thereof can be present in about 0.5 wt. % to about 2.0 wt. % of the therapeutic formulation. The sulfur can be present in about 3.0 wt. % to about 10.0 wt. % of the therapeutic formulation.
The solvent can include a polyhydric alcohol, water, or a combination thereof. The polyhydric alcohol can be propylene glycol, ethylene glycol, or a combination thereof. The propylene glycol can be present in about 3.0 wt. % to about 11.0 wt. % of the therapeutic formulation. The water can be present in about 2.0 wt. % to about 20.0 wt. % of the therapeutic formulation. The solvent can be present in about 6.0 wt. % to about 24.0 wt. % of the therapeutic formulation.
The therapeutic formulation can further include a filler. The filler can be malto dextrin. The malto dextrin can be present in about 1.0 wt. % to about 10.0 wt. % of the therapeutic formulation. The pressure sensitive adhesive can include one or more acrylic ester copolymers. The one or more acrylic ester copolymers can be present in about 3.0 wt. % to about 20.0 wt. % of the therapeutic formulation. The acrylic ester copolymer can be present in about 5.0 wt. % to about 15.0 wt. % of the therapeutic formulation. The adhesive can be positioned on the entire front side of the backing. The adhesive can be positioned on a portion of front side of the backing. The adhesive can be partially embedded in at least a portion of the backing.
The pressure sensitive adhesive can further include glycerin. The glycerin can be present in about 25.0 wt. % to about 70.0 wt. % of the therapeutic formulation. The glycerin can be present in about 45.0 wt. % to about 55.0 wt. % of the therapeutic formulation. The pressure sensitive adhesive can include an emulsifier. The emulsifier can be pectin. The pectin can be present in about 2.0 wt. % to about 10.0 wt. % of the therapeutic formulation.
The pressure sensitive adhesive can include a compound that provides structure and strength to the pressure sensitive adhesive or to the therapeutic formulation. The compound that provides structure and strength to the pressure sensitive adhesive or to the therapeutic formulation can be karaya, a polyacrylamide, xanthum gum, guar gum, a natural polymer, a synthetic polymer, a hydrophilic polymer, a hydrocolloidal polymer, starch, a starch derivative, vinyl acetate copolymer, polyvinyl pyrrolidone, polyethylene oxide, algin, derivatives of algin, a polyacrylate, polymaleic acid, polymaleic anhydride, a polyurethane, a polyurea, gum acacia, locust bean gum, modified guar gum, maltodextrin, carboxymethyl cellulose, carboxypropyl cellulose, polyvinyl alcohol, poly AMPS or a mixture thereof. The compound that provides structure and strength to the pressure sensitive adhesive or to the therapeutic formulation can be polyacrylamide. The polyacrylamide can be present in about 8.0 wt. % to about 30.0 wt. % of the therapeutic formulation. The compound that provides structure and strength to the pressure sensitive adhesive or to the therapeutic formulation can be karaya. The karaya can be present in about 8.0 wt. % to about 40.0 wt. % of the therapeutic formulation. The compound that provides structure and strength to the pressure sensitive adhesive or to the therapeutic formulation can be a combination of polyacrylamide and karaya.
The pressure sensitive adhesive can be located on the entire portion of the front side of the backing. The therapeutic formulation can further include a skin conditioner. The skin conditioner can be calamine, aloe, lanolin, glycerin, Vitamin E, Vitamin E acetate, farnesol, glycyrrhetinic acid, or any combination thereof. The aloe can be present in about 0.01 wt. % to about 2.0 wt. % of the therapeutic formulation. The Vitamin E acetate can be present in about 0.01 wt. % to about 2.0 wt. % of the therapeutic formulation.
The therapeutic formulation can further include one or more antimicrobial agents. The antimicrobial agent can be a xcex2-lactam compound, an aminoglycoside, or an antifungal agent. The antimicrobial agent can be erythromycin, tetracycline, clindamycin, or cephalosporin. The therapeutic formulation can further include one or more antiseptic agents. The antiseptic agent can be triclosan, phenoxy isopropanol, chlorhexidine gluconate, povidone iodine, or any combination thereof.
The adhesive patch can have a thickness of about 0.20 mm to about 0.75 mm. The adhesive patch can further include a release liner that is mounted on the front side of the backing. More than one patch can be mounted on the release liner. About 2 to about 20 adhesive patches are mounted on the release liner. The adhesive patch can be crescent, circular, or oval. The adhesive patch can have a diameter of about 0.1 inch to about 1.0 inch.
The portion of the backing treated with the hydrophobic sizing agent can have a surface energy of about 27 dynes/cm2 to about 56 dynes/cm2. The entire surface of the backing can be treated with the hydrophobic sizing agent. The hydrophobic sizing agent can penetrate at least a portion of the underlying surface of the backing. The hydrophobic sizing agent can penetrate the entire underlying surface of the backing.
The present invention also provides a method for treating or preventing acne or a pimple in a mammal (e.g., human) in need thereof. The method includes applying to the skin surface of the mammal having the acne or the pimple or the skin surface of the mammal at risk thereof an adhesive patch of the present invention for an effective period of time effective to treat or prevent acne or a pimple. The skin surface of the mammal having the acne or pimple or the skin surface of the mammal at risk thereof can be the face, neck, shoulder, chest, back, or any combination thereof. The effective period of time can be about one hour to about 12 hours.
The present invention also provides a method for exfoliating the skin surface of a mammal (e.g., human). The method includes applying to the skin surface of the mammal in need of such exfoliation an adhesive patch of the present invention. The adhesive patch is applied for an effective period of time after which the adhesive patch is removed, thereby effectively exfoliating the skin surface. The effective period of time can be about one second to about 12 hours.


A tube launched projectile having a shaft member at the aft section is slidably mounted on a boom extending aft from the body of the projectile. The boom has a cavity in its aft end which receives some combustion gas from the projectile propellant burn and retains this gas at elevated pressure until the projectile exits the tube. Upon reaching atmospheric pressure, the stored cavity gas expands and drives the slidable shaft aft, elongating the projectile to its flight configuration.

This invention relates in general to tube launched projectiles and in particular to tube launched projectiles which are fin stabilized or spin stabilized, where means are provided to elongate the projectile body when the projectile exits the launch tube.
Reduced length projectiles allow for reduced cost of transport and for increased launch tube propellant charge. In the case of fin stabilized projectiles the center of pressure of the fins can be relatively close to the projectile center of gravity. This configuration requires the fins be larger than for an elongated projectile to provide a restoring moment for control of the flight of the projectile. Since projectile fins typically contribute 30% to 50% of the total projectile aerodynamic drag, reductions in projectile drag would be desirable.

Lock and slide mechanism for tube launched projectiles


A treatment device is provided including a catheter having a lumen that is opened to a distal end of the catheter; a wire passing through the lumen so that the wire is inserted into or retracted from the lumen; and a piece disposed at a distal end of the wire and having the maximum width when the piece is protruded from the distal end of the catheter is set larger than the diameter of the lumen, wherein the piece body is formed of a deformable material having a broad curved surface shape that distributes concentration of pressure acting on tissues, and when the wire is pulled in toward the catheter, the piece being extended in the axial direction by the lumen and reduced in its outer diameter so as to be pulled into the lumen.

1. Field of the Invention
The present invention relates to a treatment device that is inserted through a natural orifice of a human into a duct cavity.
2. Description of Related Art
Endoscopic retrograde cholangiopancreatography (ERCP) has been known as a method of diagnosing abnormalities of the pancreas, gallbladder, or bile ducts. In ERCP, a catheter is inserted through the papilla of the duodenum, and then a contrast agent is injected directly through the pancreatic or bile ducts, thereby allowing X-ray images to be acquired.
If the entrance of the papilla is narrow or the lining of the bile duct is curved, it is difficult to insert the catheter into the bile duct. Excessive stabbing of the entrance of the papilla with the catheter may cause a mucous membrane edema, unnecessarily narrowing the entrance. Moreover, when the catheter is thrust into a submucosa through the mucous membrane when stabbing the entrance with the catheter, insertion of the catheter becomes more difficult. When a contrast agent is injected in a state that the catheter is thrust into the submucosa, the contrast agent will be injected into the submucosa so that the mucous membrane is inflated to further obstruct the entrance of the papilla. Moreover, when the edema happens or the contrast agent is injected into the submucosa to obstruct the orifice of a pancreatic duct, draining of pancreatic juice is interrupted, resulting in increasing possibility to develop pancreatitis. As another method, there is a method in which a guidewire having a flexible distal end that is relatively easily bent is protruded by about 2 to 3 mm from the distal end of the catheter to access the bile duct. Since the distal end of the guidewire is flexible but narrow, force is likely to concentrate on a single point and therefore excessive stabbing may cause an edema or the guidewire to be thrust into the submucosa. Thus, in order to prevent pancreatitis, it is necessary to decrease the risk of the edema or the puncturing of the mucous membrane as much as possible.
In the conventional procedures, the distal end portion of the catheter where an opening of the lumen for passing a contrast agent is rounded as much as possible so that the distal end portion of the catheter does not cause the edema or the puncturing of the mucous membrane.


The present invention provides a method, system and computer program product for generating a family of questions for a programming language. Generating the family of questions includes the generation of various questions from a particular compilable code, and the corresponding options for the questions. The options include various correct and incorrect options for the questions.

The present invention relates generally to question banks. More specifically, it relates to a method and system for automatically generating questions for a programming language in the question bank.
Today, software-based organizations and educational institutions are building up comprehensive infrastructure to train and evaluate their existing employees, new recruits and students. This training plays a vital role in enhancing the technical and soft skills of employees and students, who are trained on various programming languages, which require timely assessment.
A typical question for an examinee taking an examination comprises a code that can be compiled. There are several options from which the examinee has to select the correct one. Further, the question bank contains questions in various formats such as multiple choice questions, matrix questions, etc., on which the examinee is tested.
Various formats of questions are manually created and are regularly updated in the question bank. Since the number of questions in the question bank is limited, over a period of time the examinees become aware of the questions in the question bank. Further, it becomes easy for the examinee to memorize or guess the correct options for the questions without actually solving them.
Different sets of questions may be provided to examinees who are sitting near each other to reduce the possibility of their cheating from one another. This results in a difference in the difficulty level of questions in the different sets and does not assess the examinees on the same parameters.
Furthermore, incorrect options are generated for the questions, to enable the examinees to select the correct option from a set of options provided for each question. These incorrect options are quite different from the correct options, and the examinees may be able to guess the correct options easily.
In light of the foregoing discussion, there is a need for a method for updating the question bank automatically. The method should generate and populate the question bank with an unlimited number of unique questions. Further, the method should help in reducing the time required to generate the questions. The method should also help in generating correct and incorrect options for the questions, such that examinees can be evaluated for their skills and knowledge effectively.

Method and system for automatically generating questions for a programming language


A spool assembly for a dual bearing reel includes a tubular bobbin, first and second flange portions, first and second annular portions, and first and second fishing line entry prevention portions. The first and second flange portions project radially outward from opposite ends of the bobbin. Inner peripheries of the first and second annular portions cover the first and second flange portions. The first and second fishing line entry prevention portions project from outer peripheries of the first second flange portions. The first and second fishing line entry prevention portions are provided across a slight gap between tip portions of the first and second annular portions. The first and second fishing line entry prevention portions prevent fishing line from entering between the first flange portion and a first side plate and between the second flange portion and the second side plate.

1. Field of the Invention
The present invention generally relates to a spool assembly. More specifically, the present invention relates to a spool assembly for a dual bearing reel that takes up and releases fishing line.
2. Background Information
Generally, a dual-bearing reel is comprised of a reel unit having a handle and a spool that is rotatively mounted to the reel unit. The spool has a bobbin and flange portions. The flange portions are provided at both ends of the bobbin. The bobbin is for winding fishing line around the outer periphery thereof. The bobbin includes a cylindrical portion and a boss. The boss is formed on the inner peripheral side of the cylindrical portion and mounted to a spool shaft. Fishing line is wound around the outer periphery of the cylindrical portion. The flange portions have diameters that are larger than that of the bobbin. Each flange portion projects outward in the radial direction on both ends of the bobbin. The flange portions are inclined such that the diameters gradually increase outward in the axial direction.
In addition, the reel unit includes a pair of side plates and a pair of ring portions. The ring portions are configured and arranged to project inward in the axial direction and oppose the pair of side plates. The ring portions cover the outer peripheries of the flange portions. A spool is mounted between the pair of side plates. The side plates face each other across a predetermined gap. Furthermore, in order to prevent fishing line from entering between the flange portions and the ring portions, it is known to form protrusions that project radially outward on the peripheral edge of the flange portions. (See, for example, Japanese Publication No. H8-70739.)
These types of protrusions are formed so that, for example, the outer peripheral surfaces of the tip portions thereof are completely covered by the inner peripheral portion of the ring portions. A slight gap is produced between the protrusions and the ring portions. In addition, on a comparatively small reel, whose spool maximum line winding diameter is between 25 mm and 30 mm, the protrusions are formed so that the projection heights thereof are between 0.5 mm and 1.0 mm. By arranging these protrusions on the flange portions, slack fishing line will come into contact with the protrusions. The protrusions can restrict the movement of the fishing line in the axially outward direction. Thus, the entry of the fishing line between the flange portions and the ring portions can be prevented.
With a conventional spool, the protrusions are formed to project from the outer periphery of the flange portions. The flange portions are slanted so that the diameters of the protrusions gradually increase outward in the axial direction. Thus, because it is easy for slack fishing line to move axially outward along the slanted surfaces when both ends of the flange portions are slanted, it will be easy for slack fishing line to come into contact with the protrusions formed on the outer peripheries of the flange portions. Thus, when fishing line repeatedly comes into contact with the protrusions, slack fishing line may cross over the protrusions and enter between the flange portions and the ring portions or side plate.
In addition, when the protrusions are arranged so as to be perpendicular to the rotational axis of the spool, the side surfaces on the bobbin side of the protrusions (the surfaces that contact the fishing line) will intersect at an obtuse angle with the outer peripheral surfaces of the flange portions because the flange portions are slanted. Thus, when the side surfaces on the bobbin side of the protrusions intersect at an obtuse angle with the outer peripheral surfaces of the flange portions, it will be easy for slack fishing line to move outward in the axial direction from the outer peripheral surfaces of the flange portions and along the side surfaces of the bobbin side of the protrusions. Thus, fishing line may enter between the flange portions and the ring portions or side plates.
In view of the above, it will be apparent to those skilled in the art from this disclosure that there exists a need for an improved spool assembly that prevents fishing line from entering between a flange portion and a side plate. This invention addresses this need in the art as well as other needs, which will become apparent to those skilled in the art from this disclosure.


A method for handling packet discard in a transmitter of a wireless communications system includes activating a “use of a special value of a header extension field” mode, discarding a plurality of service data units, wherein the last service data unit of the plurality of service data units ends at an end of a first protocol data unit using the special value in a header extension field, and setting a value of a field to be a sequence number of a second protocol data unit, wherein the field is utilized for indicating a receiver to discard all not yet successfully received service data units that have segments with sequence number being less than the value of the field, and the second protocol data unit is next to the first protocol data unit.

1. Field of the Invention
The present invention relates to a method and apparatus for handling packet discard in a wireless communications system, and more particularly, to a method and apparatus for preventing stall of a receiving window and enhancing transmission efficiency in the wireless communications system.
2. Description of the Prior Art
The third generation (3G) mobile telecommunications system has adopted a Wideband Code Division Multiple Access (WCDMA) wireless air interface access method for a cellular network. WCDMA provides high frequency spectrum utilization, universal coverage, and high quality, high-speed multimedia data transmission. The WCDMA method also meets all kinds of QoS requirements simultaneously, providing diverse, flexible, two-way transmission services and better communication quality to reduce transmission interruption rates.
The access stratum of the 3G mobile telecommunications system comprises a radio resource control (RRC), radio link control (RLC), media access control (MAC), packet data convergence protocol (PDCP), broadcast/multicast control (BMC) and other sub-layers of different functions. The operations of the above-mentioned sub-layers are well known for those skilled in the art, and will not be further mentioned. A primary function of the RLC layer is providing different transmission quality processing, performing segmentation, reassembly, concatenation, padding, retransmission, sequence check, and duplication detection on transmitted data or control instructions based on different transmission quality requirements. The MAC layer can match packets received from different logic channels of the RLC layer to common, shared, or dedicated transport channels according to radio resource allocation commands of the RRC layer, for performing channel mapping, multiplexing, transport format selection, or random access control.
When the RLC layer operates in an acknowledged mode (AM), a header of an RLC PDU (Protocol Data Unit) comprises a two-bit HE (Header Extension) field utilized for indicating if the next octet is data or a Length Indicator (LI) and Extension (E) bit. The HE field has different values, and the corresponding description is as follows:
1. "00": The succeeding octet contains data.
2. "01": The succeeding octet contains LI and E bit.
3. "10" and "11": Reserved. PDUs with this coding represents that a protocol error is occurred, and the PDUs will be discarded.
In order to decrease overhead, the prior art can trigger a "use of the special value of the HE field" mode to set "10" of the HE field to indicate that the succeeding octet contains data and the last octet of the corresponding PDU is the last octet of an SDU (Service Data Unit). In other words, if an SDU ends at the end of a PDU, the HE field of the PDU will be set to "10." As a result, an extra PDU carrying the corresponding LI is not needed, to decrease overhead.
In some situations, such as transmission timeout or over maximum allowed times of retransmission, the transmitter can trigger an SDU discard with explicit signalling procedure, and uses an MRW SUFI (Move Receiving Window Super Field) in a STATUS PDU to request the receiver to move its receiving window to discard specified SDUs. After the SDU discard with explicit signalling procedure is triggered, the transmitter discards all SDUs to be discarded, and discards PDUs including segments of the discarded SDUs or LIs indicating the end of the SDUs. Then, the transmitter sends the MRW SUFI to inform the receiver about discarding the SDUs, so as to complete the SDU discard with explicit signalling procedure.
As mentioned above, in the "use of the special value of the HE field" mode, if an SDU ends at the end of a PDU, the extra PDU carrying the corresponding LI is not needed. In such a situation, the method of setting the contents of MRW SUFI needs to be modified, so as to support the "use of the special value of the HE field" mode.
Detail description of the MRW SUFI can be found in the related protocol specification. The MRW SUFI comprises fields of:
1. LENGTH: The number of discarded SDU.
2. SN_MRWi: Each SN_MRW is used to indicate the end of each discarded SDU. The last SN_MRW, i.e. SN_MRWLENGTH requests the receiver to discard all not yet successfully received SDUs that have segments or LIs indicating the end of the SDUs in the PDUs with Sequence Numbers <SN_MRWLENGTH.
3. NLENGTH: NLENGTH is used together with SN_MRWLENGTH to indicate the end of the last SDU to be discarded in the receiver.
To support the "use of the special value of the HE field" mode, the prior art provides operations for setting the MRW SUFI as follows. If the "use of the special value of the HE field" mode is triggered, and the last SDU to be discarded ends at the end of a PDU, i.e. the PDU does not contain an LI corresponding to the last SDU to be discarded, then the prior art sets the SN_MRWLENGTH to be a sequence number (SN) "a" of the PDU, and sets NLENGTH to be "0000." Thus, the receiver will advance its receiving window to start from SN=a. However, as mentioned above, after the SDU discard with explicit signalling procedure is triggered, the transmitter discards all SDUs to be discarded, and discards PDUs including segments of the discarded SDUs or LIs indicating the end of the SDUs. In other words, PDU with SN=a has been discarded by the transmitter in this example, and will not be transmitted to the receiver. In such a situation, the receiver waits for the PDU with SN=a, so that the receiving window is stalled until another MRW procedure is triggered. The transmission efficiency and transport data rate are reduced.
In short, when the "use of the special value of the HE field" mode is triggered, and the last SDU to be discarded ends at the end of a PDU, the prior art sets SN_MRWLENGTH to SN of the PDU, to advance the receiving window of the receiver to start from the SN of the PDU. However, since the PDU has been discarded by the transmitter, the receiver cannot receive the PDU anymore, causing stall of the receiving window and degradation of transmission efficiency.

Method and related apparatus for handling packet discard in a wireless communications system


An electrophoresis device is disclosed that is capable of reducing waves occurring in a fluid in which the capillary tips of a capillary assay are immersed. A plurality of partition plate members can be provided in a container containing the fluid to divide the surface of the fluid into several sections. The container can be transported at a high speed, and the capillary tips can be immersed in the fluid quickly, thereby preventing resolution degradation caused by a long period of exposure of the capillary tips to air. Throughput of sample analysis can also be improved because it is not necessary to wait until waves disappear before conducting an analysis.

An example of a known device includes the Genetic Analyzer 3100, manufactured by Applied Biosystems. This analyzer can contain a buffer and a washing solution in a generally rectangular parallelepiped container having a smooth inner face. The analyzer can have a sample container, a buffer container, a washing solution container, and a waste liquid container on the same platform. Analyses can be carried out by moving the platform.


A method and apparatus for an integrated circuit package is provided. The integrated circuit package is designed for coupling an integrated circuit to a printed circuit board. The integrated circuit package includes a base having a bottom and a side. A flex circuit having traces therein is coupled to the base. The traces in the flex circuit are designed to couple to the leads of the integrated circuit. The traces further are designed to couple to traces on the printed circuit board.

A semiconductor device is typically packaged as a chip and mounted on a circuit board to mechanically and electrically connect the semiconductor device to the circuit board. This allows the semiconductor device to be electrically coupled to various other devices within a digital data processing system.
One known package type is a surface vertical package ("SVP"), which provides for the edge-mounting of chips to circuit boards. The semiconductor device is packaged in a relatively flat package such that the leads that provide for electrical connections to the semiconductor device are positioned on one edge of the chip. Typically a semiconductor die containing an integrated circuit--which can be a semiconductor memory, processor, or ASIC, for example--resides in the center of a plastic package. Wires within the plastic package connect the semiconductor die with the leads, which reside on one end of the plastic package.
Each lead of the SVP chip is soldered to a respective solder pad on a circuit board to mechanically and electrically connect the semiconductor device to the circuit board. In the prior art, the leads of the SVP chip are bent substantially perpendicular relative to the SVP package so that the SVP chip is placed upright over the circuit board in soldering each lead to its respective solder pad. The SVP chip may have, at its bottom edge, supporting pins to help the SVP chip stand upright in soldering the SVP chip to the circuit board.
One problem with the prior SVP chip is that the electrical connection between the SVP chip and the circuit board is not of sufficiently high quality to handle extremely high frequencies and low voltage swings without electrical degradation.
Another disadvantage of the prior SVP chip is the difficulty in placing a large number of leads on one side of the SVP chip without having shorts between leads when the leads are soldered to the circuit board.
Another disadvantage of the prior SVP chip is that pressure applied to the SVP chip can lead to fractures in the leads, or short circuits, which in turn can lead to a loss of signal and a loss of data.
Another disadvantage of the prior SVP chip is the relative difficulty involved in installing and removing an SVP chip.

Integrated circuit package for coupling to a printed circuit board


The invention relates to novel substituted pyrazolo[4,3-e]-diazepines of general formula:

Cyclic adenosine 3′,5′-monophosphate (cAMP) is a ubiquitous intracellular second messenger, which is intermediate between a first messenger (hormone, neurotransmitter or autacoid) and the cellular functional responses: the first messenger stimulates the enzyme responsible for the synthesis of cAMP; depending on the cells concerned, the cAMP then intervenes in a great number of functions: metabolic, contractile or secretory.
The effects of cAMP end when it is degraded by cyclic nucleotide phosphodiesterases, which are intracellular enzymes that catalyse its hydrolysis into inactive adenosine 5′-monophosphate.
At least 11 major families of cyclic nucleotide phosphodiesterases (PDE) have been distinguished in mammals, numbered from 1 to 11 according to their structure, their kinetic behaviour, their substrate specificity or their sensitivity to effectors (Beavo J. A. et al. (1990) Trends Pharmacol. Sci. 11, 150–155. Beavo J. A. et al. (1994) Molecular Pharmacol. 46, 399–405). The PDE4 enzymes are specific for cAMP.
Non-specific phosphodiesterase inhibitor compounds are known, which inhibit several families of enzymes. This is the case for certain methyl xanthines such as theophylline. These compounds have a low therapeutic index, in particular on account of their action on types of PDE present in cells other than the target cells. Conversely, certain families of PDE can be selectively inhibited by various pharmacological agents: the hydrolysis of cyclic nucleotides is slowed down and their concentration thus increases in only the cells in which the type of PDE that is sensitive to the inhibitor is found.
A specific advantage is shown for the phosphodiesterases 4 (PDE4), which have been identified in many tissues including the central nervous system, the heart, vascular endothelium, vascular smooth muscle and that of the aerial pathways, myeloid lines and lymphoid lines.
An increase in cAMP in the cells involved in inflammation inhibits their activation: inhibition of the synthesis and release of mediators in mastocytes, monocytes, polymorphonuclear eosinophils and basophils, inhibition of chemotaxis and degranulation of polymorphonuclear neutrophils and eosinophils, inhibition of the proliferation and differentiation of lymphocytes.
Cytokines, in particular TNF and interleukins, produced by various types of leukocytes such as the T lymphocytes, monocytes and polymorphonuclear eosinophils, play an important role in triggering inflammatory manifestations, in particular in response to stimulation by an allergen in the respiratory pathways.
Moreover, cAMP reduces the tonus of the smooth muscle fibres in the aerial pathways.
It might thus be expected that selective PDE4 inhibitors would have therapeutic activity as anti-inflammatory and anti-allergic medicinal products, and in the treatment of various respiratory diseases such as asthma, emphysema and chronic bronchitis.
Extensive research has been conducted for several years into the production and development of powerful PDE4 inhibitors. This is found to be difficult due to the fact that many potential PDE4 inhibitors are not devoid of activity on the phosphodiesterases of other families.
At the present time, the lack of selectivity of PDE4 inhibitors thus represents a major problem, given the extent of the functions regulated by cAMP. There is thus a need for powerful and selective PDE4 inhibitors, i.e. inhibitors which have no action with respect to PDEs belonging to other families and particularly PDEs which regulate cGMP.

Substituted pyrazolo[4,3-e]diazepines, pharmaceutical compositions containing them, use as medical products and processes for preparing them

Abstract: to pharmaceutical compositions containing them, to their use as medicinal products and to processes for preparing them.


A motor. The motor includes a stator, a rotor, a top magnetic structure, and a bottom magnetic structure. The stator is disposed in a frame. The rotor is also disposed in the frame, corresponding to the stator. The rotor comprises a shaft, extended axially from the rotor. The shaft does not contact the stator or the frame. The bottom magnetic structure is at the bottom of the frame. The top magnetic structure is on the top of the frame. The top and bottom magnetic structures are opposite to each other in an axial direction. Magnetic attraction generated between the first magnetic structure and the second magnetic structure attracts and positions the shaft therebetween such that the first magnetic structure, the second magnetic structure, and the shaft are coaxially aligned.

1. Field of the Invention
The present invention relates to a motor, and in particular to a high power motor not utilizing bearings.
2. Description of the Related Art
A conventional motor comprises a shaft, a rotor, and a bearing. The rotor is disposed on the shaft and supported by the bearing, enabling the rotor to rotate smoothly.
Mechanical components reducing friction and bearing loads in rotary and linear drives include ball and roller bearings, sleeve bushings, dynamic bearings, magnetic bearings, and other configurations.
A ball bearing comprises an outer ring, an inner ring, and a plurality of metal balls disposed therebetween. The ball bearing is actuated by rolling of the metal balls. Only one contact point between the metal balls and the inner or outer ring allows easy acceleration of the motor. The structure of the ball bearing, however, is weak and susceptible to impact. In addition, when the motor with the ball bearing is operated, the balls roll at high speeds, resulting in producing high noise level. The structural interface between the balls and the inner and outer rings requires a high degree of accuracy, thus increasing manufacturing costs.
A sleeve bearing is formed by mixing and sintering bronze powder, iron powder, nickel powder, lead powder and other metal powders. Lubricant is applied into the pores of the bearing. The sleeve bearing, when disposed in a motor, is fastened in the central position of the stator. The shaft of the rotor is disposed in the bearing such that a gap is maintained between the bearing and the shaft. When the motor is operated, the lubricant exudes from the bearing such that the rotor rotates in the lubricant. This type of bearing can sustain higher impact than the ball bearing, and manufacturing costs are also reduced. In a motor utilizing the sleeve bearing, however, the lubricant evaporates into gaseous phase as the bearing is operated over long periods. As a result, the shaft directly contacts the bearing such that friction is produced therebetween. Furthermore, nitrides can possibly form at the ends of the bearing, causing damage and increasing noise level. In addition, dust in the air may be drawn into the center of the motor during operation, contaminating the lubricant surrounding the bearing, increasing noise level and occluding moving parts. Furthermore, since the gap between the bearing and the shaft is small, the efficiency in starting the motor is reduced.
A dynamic bearing is a variation of the sleeve bearing. This type of bearing comprises an inner wall with two annular arrays of V-shaped grooves formed therein. During operation, air and lubricant are impelled toward the pointed ends of the grooves forming two oil-gas cushions to support the shaft. In a motor with this type of bearing, the oil-gas cushion, formed at the pointed end of the V-shaped groove, is unable to be dispersed or evaporated. Formation of the groove on the inner side of the dynamic bearing, however, requires precise manufacturing. Furthermore, the gap between the shaft and the bearing must be accurately maintained. Thus, the manufacturing cost is higher than other types of bearings. Moreover, when the motor operates at low speed, the oil-gas cushion is not formed. Thus, the dynamic effect is not achieved at low speeds, such that performance of the dynamic bearing is substantially the same as a sleeve bearing.
A magnetic bearing has a plurality of N-S (north-south) magnetic poles formed on the shaft. The bearing corresponding to the shaft has the same N-S poles formed thereon. During operation, repellant force suspends the shaft in the bearing. Because there is no direct contact between the shaft and the bearing, neither noise nor friction is generated therebetween. The magnetic bearing, however, must be designed with a gap of about 0.2 mm between the shaft and the bearing, such that balanced force toward the center point is generated by each portion of the bearing surrounding the shaft. However, if the position of the shaft is offset by external force or driving force during operation, the imbalance can cause shaft contact with the bearing. This increases noise, shortens lifetime, and can even interrupt normal operation of the motor.
Furthermore, since the magnetic bearing is based on magnetic balance, there are occasions that the motor cannot be smoothly started. Thus, the magnetic bearing is still in an experimental stage, as yet unable to be mass produced.

Fan assembly with magnetic thrust bearings


A method of diagnosing arterial stenosis from a received Doppler shifted acoustic signal from an artery during multiple heartbeats, each having systolic and diastolic phases uses pattern recognition techniques that are applied to the signal to determine the presence of turbulence during the diastolic phases which indicates stenosis. This is advantageously done by comparing the systolic and diastolic phases as part of the pattern recognition technique, large differences being indicative of a healthy artery and smaller differences being indicative of stenosis.

The present invention relates in general to cardiovascular diagnosis techniques, and in particular to a new, simple, inexpensive yet accurate system for the diagnosis of arterial stenosis, that is, cholesterol deposits in the carotid artery.
The carotid artery is the artery that carries blood from the heart to the brain. Carotid arterial stenosis is a cerebrovascular disease that is caused by cholesterol deposits inside the artery. These deposits clog the artery and prevent the normal flow of blood. During the systolic cycle, the heart pumps blood into the arterial system, the velocity of blood is high, and the flow of blood is turbulent even if there is no stenosis. If the artery is "clean" there is no turbulence inside the artery during the diastolic cycle when the heart does not pump and when blood flows slowly in the opposite direction due to the elasticity of the arterial system. However, if there are deposits inside the carotid artery (stenosis) the flow of blood will be turbulent even during the diastolic cycle.
The "Doppler frequency-shift effect" was predicted by the astronomer Christian Doppler in 1842 and was experimentally confirmed in 1845. It was 30 years after ultrasound had been used in the military to detect submarines, that the first practical ultrasonic Doppler device for use in medicine was designed and constructed by Satomura in 1956.
Three decades later, there has been a widespread expansion of Doppler ultrasonic applications into virtually all areas of cardiovascular diagnostics.
According to the Doppler effect, a reflected frequency from a moving object will be shifted from the original transmitted frequency. The arterial Doppler signal is formed as follows: an ultrasonic transducer is placed in contact with the skin surface, and the ultrasound beam whose frequency is f.sub.o is directed toward the blood vessel. The source of the echo signals are the red blood cells flowing in the vessel. The reflected signal frequency is denoted as f.sub.r. The Doppler frequency shift, f.sub.D, will be related to the velocity of the reflector, v, by the equation, EQU f.sub.D =(2f.sub.o v/c) cos .THETA. (1)
where c is the speed of sound and .THETA. is the angle between the direction of the blood flow and the ultrasonic beam. It can been seen that f.sub.D will change along with changing .THETA.. When .THETA.=90.degree., cos .THETA.=0, which is an undesirable situation because no Doppler shift will be detected. In practice, the transducer is usually oriented and fixed to make a 30.degree.-60.degree. angle with the arterial lumen to ensure the correct measurement of v.
Since all reflectors flowing at different speeds within the sound beam are contributing to the Doppler frequency shift, f.sub.r, the output f.sub.D is a complex signal occupying a wide frequency range.
Whenever an ultrasound beam strikes an interface formed by two tissues having different acoustic properties, part of the beam is reflected and part is transmitted. If the reflected wave travels back toward the ultrasound source, it may be detected as an echo. The amplitude of the reflected wave is determined by the different in acoustic impedances of the material forming the interface.
The acoustic impedance, Z, is the speed of sound in a material multiplied by its density. For a perpendicular angle of incidence of an ultrasound beam on a large, flat interface, the ratio of the reflected to the incident amplitude, R, is given by EQU R=(Z.sub.2 -Z.sub.1)/(Z.sub.2 +Z.sub.1) (2)
where Z.sub.1 is the impedance of the substance in which the reflected beam will travel, and Z.sub.2 is the impedance of the substance in which the incident beam travels. Equation (2) shows that the larger the difference between Z.sub.1 and Z.sub.2, the more energy is reflected and the greater is the echo.
Despite the existence of Doppler effect techniques used for measuring the acoustic properties of living tissues, a need remains for a simple reproducible, non-invasive technique for detecting when and how much cholesterol has deposited in an individual's arteries.

Detection of cholesterol deposits in arteries


A method and system for inserting hand-written text is disclosed. The method includes detecting, from a stylus, an insertion gesture on a touch screen, determining, on the touch screen, an insertion location where the hand-written text is to be inserted, generating, on the touch screen, an insertion box for receiving the hand-written text from the stylus, detecting, from the stylus, the hand-written text in the insertion box, and, in response to determining that the hand-written text nears or exceeds a boundary of the insertion box, increasing a size of the insertion box to accommodate the hand-written text. The method further includes detecting, from the stylus, a completion gesture on the touch screen, reducing the size of the insertion box to encapsulate the inserted hand-written text, and erasing the insertion box and inserting the hand-written text into a space previously occupied by the insertion box.

Note-taking applications are one of the most popular applications on pen-based devices. When using note-taking applications, users may need to edit the contents by erasing, selecting, and inserting text. Some applications allow users to perform these operations by gestures. Current technology allows for using gestures to insert typed text between other typed text, or to convert handwritten text into typed text and insert it between other typed text.


The present invention relates to a method for warning a driver of a motor vehicle (2) of an obstacle (1) present in a side area (19) next to a side flank (13) of the vehicle (2) with the help of a driver assistance system (3), wherein during a motion of the vehicle (2) the obstacle (1) is detected by an ultrasonic sensor (5, 7) stationarily arranged on a vehicle bumper (6, 8), before the obstacle (1) leaves a detection area (10) of the ultrasonic sensor (5, 7) and enters the side area (19) next to the side flank (13). After the obstacle (1) leaves the detection area (10) a current position of the obstacle (1) in the side area (19) relative to the vehicle (2) is estimated by the driver assistance system (3), wherein the driver is warned by the driver assistance system (3) in dependency on a result of the estimation.

The present invention relates to a method for warning a driver of a motor vehicle of an obstacle present in a side area next to a side flank of the vehicle with the help of a driver assistance system. During a motion of the vehicle—forward or backward—the obstacle is detected by an ultrasonic sensor stationarily arranged on a vehicle bumper. The obstacle is detected before it leaves a detection area of the ultrasonic sensor and enters the side area next to the side flank of the vehicle. Furthermore, the present invention relates to a motor vehicle comprising a driver assistance system which is designed for performing such a method.
Driver assistance systems for warning the driver of an obstacle present in a side area next to the side flank of the vehicle are already known from the prior art. Also, it is prior art that obstacles can be detected by means of an ultrasonic sensor arranged on a vehicle bumper, a front bumper or rear bumper. The detection of obstacles using standard ultrasonic sensors—i.e. sensors located stationarily at the front or at the rear of the vehicle—is limited during sharp turns. Initially, an obstacle present in front of or behind the vehicle can be detected by the sensor. Even if the detected obstacle is initially not in the path of the car, it can become present in the path after the sensor loses touch with the obstacle, i.e. after the obstacle enters the side area next to the side flank of the vehicle. Then, the sensor can no longer monitor the obstacle, and a collision can occur between the vehicle and the obstacle.
The prior art faces this problem as follows: Document EP 1 447 271 A2 discloses a driver assistance system for monitoring an area close to a motor vehicle. This system comprises an ultrasonic sensor located on a side flank of the vehicle. Thus, a collision between the side flank and the obstacle can be prevented. The current position of the obstacle can also be tracked depending on the path of the vehicle determined by a path sensor. In order to prevent a collision with the obstacle, the system provides a warning signal tone or automatically brakes the vehicle. So, the obstacle is detected based on an ultrasonic sensor located on the side flank of the vehicle. However, not all vehicles are equipped with such a sensor.
Moreover, document JP 06189610 A describes a motor vehicle comprising an ultrasonic sensor located in the front of the vehicle. The adjustment of the sensor can be changed and regulated. Thus, the detection direction of the sensor can be changed together with the turning direction according to the steering angle.
Furthermore, document JP 2004 351 992 A discloses a driver assistance system for a motor vehicle. The system can compute a possible path of the vehicle depending on the current steering angle measured by a steering angle sensor. Thereafter, the system inclines one ultrasonic sensor in the opposite direction and one sensor in the same direction as the steering direction. Thus, obstacles can be detected which are present on the vehicle path.
So, in the prior art a sensor located at the side flank of the vehicle or a movable sensor is required for warning the driver of an obstacle present in the side area next to the side flank of the vehicle. Thus, it is a challenge to provide a method for preventing a collision between an obstacle and the side flank of the vehicle using only a single ultrasonic sensor located at the front or at the rear of the vehicle.
An object of the present invention is to provide a solution as to how a driver of a motor vehicle can be warned of an obstacle present in a side area next to a side flank of the vehicle using a standard ultrasonic sensor stationarily located at the front or at the rear of the vehicle.
This problem is solved—according to the invention—by means of a method with the features according to patent claim 1 as well as by means of a motor vehicle with the features of patent claim 15. Advantageous embodiments of the invention are subject matter of the dependent claims and of the description.

Method for warning a driver of a motor vehicle of an obstacle present in a side area next to a side flank of the vehicle and motor vehicle with a driver assistance system


A short detection circuit, for detecting an output node corresponding to an output voltage converted from an input voltage of a power converter, includes a first current source, a charging/discharging unit, a comparator, and a logic control unit. The charging/discharging unit performs charging operation in accordance with the first current source to generate a charging signal in a shorted condition of the output node. The comparator outputs an enable signal by comparing the charging signal with a reference signal. The logic control unit is controlled by the enable signal to generate a fault signal for turning off a first switch coupled between the output node and the input voltage in the shorted condition of the output node. A method for detecting short of an output node corresponding to an output voltage converted from an input voltage of a power converter is also disclosed herein.

1. Field of Invention
The present invention relates to a short detection circuit. More particularly, the present invention relates to a short detection circuit of a power converter.
2. Description of Related Art
White light-emitting diodes (LED) have been more and more popularly employed in liquid crystal display panels. Conventionally, single one driving IC can be designed with high voltage and large current to drive as many LEDs as possible. Thus, how to detect and protect the driving IC and the associated LEDs is important.
When the output node or output pin (e.g. LX) of the driving IC is short, an error amplifier is usually utilized to detect voltage levels such that the over-current protection (OCP) can be thus performed. However, the over-current protection performed by utilizing the error amplifier can possibly fail in some conditions. Therefore, a more assured and securer manner for detecting and protecting the whole circuit should be provided.

Power converter, short detection circuit thereof, and method for detecting short


Systems and methods which implement hybrid postage printer technology are shown. Embodiments provide a postage printing apparatus having a printable area larger than that associated with a postage meter stamp printed thereby and which can accommodate a variety of mail item and other media sizes. Embodiments employ a movable platen to accommodate various media thicknesses. Embodiments accommodate any size mail item or other media using a “C” configuration to allow a mail item or other media to extend beyond the print mechanism in at least three directions. According to an embodiment, the postage printer includes a web browser for hosting postage generation client software and to communicate with a postage generation server via the Internet or other network. Embodiments utilize a commercially available ink cartridge filled with a ink unique to postage metering applications and one or more color ink cartridges.

Postage meters or franking devices have been in widespread use for many years. Such meters have traditionally been provided as a dedicated apparatus or "closed" system imprinting a postage indicium on postal items. U.S. Pat. No. 3,194,946 shows one example of a closed metering system.
In more recent years, the concept of an "open" metering system has been developed which utilizes a general purpose processor-based system, such as a personal computer system, operable under control of an instruction set defining operation as a postage metering apparatus. U.S. Pat. Nos. 5,606,507 and 6,385,731, the disclosures of which are incorporated herein by reference, show examples of open metering systems.
Closed metering systems have generally been relatively easy to operate, requiring only that the user insert a mail piece or label, set a desired amount of postage, and activate the printing mechanism to obtain a postage meter stamp. However, closed metering systems suffer from an inability to perform additional functions, not being flexible with respect to a user's changing needs or accommodating upgrades as new technologies develop, and being limited in the size and what can be printed as or with the postage meter stamp.
For example, even the more modern closed metering systems which print information based postage indicia provide a print area limited to a single corner of an envelope or other media. Specifically, such closed meter systems generally implement ink nozzle (often referred to as ink jet) print cartridge technology which provides for an approximately 0.5 inch print width. This ink cartridge is often mounted on a carriage which allows approximately 2 inches of movement along an X axis. The carriage itself is movable along a Y axis to accommodate two-pass printing by the ink cartridge to "stitch" together an image twice as wide as the ink cartridge print width (e.g., providing a print form factor of approximately 1 inch along the Y axis by approximately 2 inches along the X axis).
In contrast to closed metering systems, open metering systems utilize general purpose systems which may be used to perform many functions in addition to postage metering. Moreover, open metering systems may typically be upgraded to include new features and new technologies by a simple software upgrade and/or addition of peripheral components. Many open metering technologies, such as that provided by Stamps.com, Santa Monica, Calif., implement an Internet architecture, facilitating enhanced services such as address verification, online delivery notification, etcetera. Open metering systems have generally utilized general purpose printers, such as laser printers or ink nozzle (often referred to as ink jet) printers, and thus provide flexibility in the size and content of what is printed as or with the postage meter stamp.
Many closed meter users have been reluctant to adopt the open metering technology despite advantages in flexibility associated therewith. For example, a traditional closed meter user expects to simply input a postage amount and print a postage meter stamp without the need to interface with a general purpose computer and its attendant software etcetera. Because the printers used in open metering systems are often general purpose printers, a traditionally closed meter user may experience difficulty in properly orienting and inserting an envelope for printing. Moreover, the closed meter user typically applies a postage meter stamp to a completed mail item (e.g., an envelope stuffed with one or more documents) which cannot be accommodated by general purpose printers. However, many open meter users prefer the use of open metering technology in order to obtain benefits such as the ability to print various configurations of postage meter stamps, the ability to print information (e.g., addressor address, addressee address, message, advertising logo, etcetera) in association with postage meter stamps, and various value added services (e.g., address verification, online delivery confirmation, detailed account activity analysis and reporting, etcetera).

Hybrid postage printer systems and methods


Mechanical actuating device for opening or closing a valve of at least one nozzle, the nozzle moving along a path preset with respect to a support. The valve comprises a mobile control unit which is movable between an open position and a closed position, and elements for mechanically moving the control unit including at least one guide rail fitted with a flexure in the area of the open or closed position enabling the control unit to switch from one position to the other.

1. Field of the Invention
The present invention relates to a mechanical actuating device for opening or closing a valve that controlling a nozzle movable along a present trajectory with respect to a support.
2. Discussion of Background Information
More especially, this actuating device finds application on carriage construction machinery, such as finishers, for instance of the same type as those described in commonly assigned application for French patent FR-90.06306 dated May 21, 1990, entitled "Spreading device for a fluid material or analogical, especially a bonding emulsion for bituminous coated materials, over a road surface and carriage way construction machinery, especially finishers, comprising such a device", which was published as FR-A-2,662,193 on Oct. 30, 1992, and is a family member of U.S. patent application Ser. No. 07/685,952, filed Apr. 17, 1991. The finishers described in this application are fitted with a spreading assembly enabling the spreading of bonding emulsion for bituminous coated materials, together with applying the coated materials over the road surface. This spreading assembly comprises mainly, on a mobile finishing vehicle, at least one spreading rail fitted with nozzles, and in order to perform the spreading operation of the whole width of the road, a mechanism for moving the spreading rail from one side to the other, transversely with respect to the displacement direction of the mobile finishing vehicle.
It has appeared necessary, especially for adjusting the spreading width, to add a device to control the opening or the closing of the nozzles when they pass through a given point on their transverse path with respect to the chassis of the mobile finishing vehicle. This point may be a limit of the spreading width, for instance.
A classic remedy for this problem would have consisted of using servovalves. But the spreading assembly would have been far more expensive and far more complex.
By the present invention there is provided an actuating device, for opening or closing a valve controlling a nozzle, which is exclusively mechanical.

Mechanical actuating device for opening or closing a valve controlling a nozzle movable along a present trajectory


An optical board including a substrate including a plate-shaped resin including a first main plane and a second main plane facing each other, and a slit-shaped optical fiber receiving portion which penetrates between the first main plane and the second main plane in a thickness direction, a metal layer provided on the second main plane, and a wiring pattern consisting of metal and provided on the first main plane. An inclined plane is provided at an end of the optical fiber receiving portion in the substrate, a tilt angle of the inclined plane with respect to the first main plane is an obtuse angle, and a reflective layer is provided on the inclined plane for reflecting a light output from an optical fiber received in the optical fiber receiving portion toward the first main plane.

1. Field of the Invention
The present invention relates to an optical board, a method for manufacturing an optical board, and an optical module structure, more particularly, to an optical board for receiving an optical fiber, a method for manufacturing the same, and an optical module structure with an optical board.
2. Description of the Related Art
Conventionally, an optical mounting board which has a groove for holding an optical fiber and on which a photoelectric conversion device is mounted has been known as disclosed by Japanese Laid-Open Publication No. 2003-167175 (JP-A 2003-167175).
The optical mounting board disclosed by JP-A 2003-167175 is formed by pressing a die having a triangular pole-shaped protrusion (a protrusion having a triangular cross section) on a substrate material which is softened. On the optical mounting board, a guide groove with a shape corresponding to the protrusion of the die is formed and a tapered plane is formed at an end of this guide groove. A reflecting plane is formed by plating a metal layer or pasting a mirror on the tapered plane to reflect an output light of the optical fiber held in the guide groove toward a light receiving element.

Optical board, method for manufacturing the same, and optical module structure


A substantially pure S1-3 protein (a) being a DNA binding protein containing three zinc finger domains, (b) whose mRNA is overexpressed in senescent human diploid fibroblasts or human diploid fibroblasts derived from a patient with Werner Syndrome, and (c) whose mRNA is not expressed in fetal human diploid fibroblasts.

Replicative senescence, the finite replicative limit of human diploid fibroblasts
Biological aging, an inevitable process common to multicellular organisms, involves a progressive physiological decline and associated pathologic degeneration of tissues and organs. The fundamental basis of aging remains enigmatic (Goldstein, 1992; Dice, 1993). The discovery that human diploid fibroblasts (HDF) have a finite proliferative lifespan opened the way to explore aging at the cellular level (Hayflick, 1965). The major feature of senescent HDF is their inability to synthesize DNA due to G1 arrest and failure to traverse the G1/S boundary (Goldstein, 1990; Cristofalo and Pignolo, 1993). A further hallmark of senescence is the dominant effect of the senescent nucleus on DNA synthesis in the young nucleus, as demonstrated in experiments involving somatic cell fusions between young and old cells. Initiation of DNA synthesis in the young HDF nucleus was extinguished, but ongoing DNA synthesis was not (Norwood et al., 1974; Stein and Yanishevsky, 1981). Moreover, this effect is abrogated by blockers of RNA and protein synthesis indicating that inhibition of DNA synthesis depends upon one or more proteins and perhaps on a direct inhibitory action of RNA(s) (Norwood et al., 1990).
Human diploid fibroblast cells (HDF) cultured in vitro provide an excellent model system for the study of biologic aging (Hayflick 1965; Goldstein 1990). These cells possess a limited replicative lifespan ("senescence in vitro"), that can be measured as the MPD.sub.max, the maximum number of Mean Population Doublings accruing until phaseout. However, the great majority of senescent cells remain viable and capable of carrying out all metabolic and macromolecular functions except semiconservative DNA synthesis.
In several large series of HDF cultures, the MPD.sub.max is inversely proportional to the age of the donor (reviewed in Goldstein 1989). Moreover, HDF from subjects with Werner syndrome (WS, see below for discussion) display a sharply curtailed growth capacity compared to age-matched controls (Thweatt, et al. 1993). Thus, physiologic rather than chronologic age determines the MPD.sub.max, and HDF clearly count cell divisions, rather than calendar or metabolic time, to a critical limit (Goldstein 1990; Goldstein 1989). That the replicative lifespan of cultured fibroblasts from a diversity of animal species is directly proportional to the maximum life expectancy of these species (ranging from two years to 150 years) indicates the presence of powerful genetic determinants of cellular senescence (Goldstein 1990; Goldstein 1992). Taken together, the data suggest a critical connection between senescence of HDF in vitro and biologic aging in vivo.
Dominance of the senescent phenotype in HDF
Cell fusion experiments have guided the search for root causes of HDF senescence. In repeated attempts at forming proliferating cell hybrids, young HDF (yHDF) failed to rescue senescent HDF (SHDF) after cell fusion, but permanent lines were able to do so (Goldstein, 1971). In short-term cell hybrids containing a senescent and a young nucleus within a single cytoplasm, i.e. heterocaryons, initiation of DNA synthesis in the yHDF nucleus was extinguished (Goldstein, 1971) but ongoing DNA synthesis was not (Yanishevsky, et al. 1980; reviewed in Norwood, et al. 1990). Brief post-fusion treatment of such heterocaryons with blockers of RNA and protein synthesis abrogated the inhibition (Norwood, et al. 1990).
Taken together, these data indicate that senescence is a dominant trait mediated by proteins or perhaps RNAs. In strong support of this concept, Lumpkin, Smith and coworkers microinjected polyA.sup.+ RNA from sHDF into yHDF and were able to inhibit DNA synthesis (Lumpkin, et al. 1986).
Relationship between HDF senescence and negative growth regulation
The primary mechanism by which senescent cells irreversibly lose the ability for transit through the G1/S checkpoint of the cell cycle, which differentiates them from growth arrested (quiescent) cells, is yet to be discovered. It is obvious that quiescence (arrested) and senescence share many proteins in common whose activity lead to the inhibition of DNA synthesis. Recently discovered proteins controlling cell cycle progression belong to this category. Their function is to inhibit activity of cyclin dependent kinase-cyclin (CDK-cyclin) complexes. These proteins are termed CDK inhibitory proteins (CKIs) and appear to be responsible for braking the cell cycle. Some of these proteins are activated in response to extracellular signals, while others appear to function intrinsically during the cell cycle (reviewed in Hunter 1993 and Peters, et al. 1994).
The p21 protein was initially identified by functional cloning of a gene sequence (SDI1) coding for an inhibitor of DNA synthesis and is overexpressed in sHDF at a level approximately 10-20 times the level seen in yHDF (Noda, et al. 1994). The identical protein was discovered virtually simultaneously by three other laboratories investigating systems unrelated to senescence, p21 and CIPI were isolated by their ability to bind and inhibit Cdk2-cyclin A and Cdk2-cyclin E complexes activities (Xiong, et al. 1993; Harper 1993), and WAF1 was induced by p53 protein in response to DNA damage, leading to transient cell cycle arrest by inhibiting CDKs (El-Deiry, et al. 1993; Dulic, et al. 1994).
Another negative regulator of cell cycle transit named p16, identified by its association with Cdk4 in the yeast two-hybrid protein interaction system, appears to specifically inhibit Cdk4-cyclin D kinase activity in vitro (Serrano, et al. 1993). A major target of this kinase seems to be the retinoblastoma product (Rb), which must be phosphorylated for proper progression through GI phase. Available data support the proposal that p16 prevents phosphorylation of Rb (Serrano, et al. 1993). Closely related studies, primarily by Stein and co-workers, have analyzed the role of Rb in HDF senescence. Following serum stimulation Rb remains underphosphorylated in sHDF, in contrast, phosphorylated Rb is abundant following serum stimulation of quiescent (arrested) yHDF (Stein, et al. 1990). Moreover, underphosphorylated Rb in sHDF is associated with the failure to express Cdc2, cyclin A and cyclin B (Stein, et al. 1991; Richter, et al. 1991), the inability to phosphorylate the Cdk2-cyclin E complex (despite its elevated protein level), and the attenuation of Cdk2-cyclin D1 and Cdc2-cyclin A complexes activities (Dulic, et al. 1993). The intrinsic cell cycle machinery is controlled by external signals such as growth factors and antimitogens which allows for coordination of cell division with environmental and developmental stimuli. TGF-.beta. which can exhibit antimitogenic activity (Moses, et al. 1990) is known to play a role in expression of certain mRNAs and proteins like fibronectin, .alpha.(I)collagen, thrombospondin and SPARC/osteonectin (Penttinen, et al. 1988; Reed, et al. 1994), which are overexpressed in sHDF and WS HDF (Murano, et al. 1991), and also has been associated with the inhibition of the Cdk2-cyclin E complex kinase activity (Koff, et al. 1993). The protein responsible for this inhibition, p27, recently has been identified as associated with the Cdk2-cyclin E complex in cells arrested by TGF-.beta. (Polyak, et al. 1994; Polyak, et al. 1994; Toyoshima, et al. 1994). p27 also appears to be involved in cell cycle arrest imposed by contact inhibition (Polyak, et al. 1994).
Transcription factors and their role in senescence
Senescing cells undergo changes which suggest altered transcriptional regulation of gene expression. Because transcription factors are attractive candidates which may ultimately specify the senescent phenotype, many studies have been performed to describe the expression and activity of known transcription factors in senescent cells. These studies revealed that E2F transcription factor which is a positive regulator of several late G1 phase genes required for G1/S transition, is underexpressed in senescent cells and its activity is negatively regulated by the unphosphorylated form of Rb (Dimri, et al. 1994; Nevins 1992; Flemington, et al. 1993). Moreover in sHDF genes coding for transcription factors involved in the immediate early response to growth factors such as c-fos, Id-1h and Id-2h, appear to be irreversibly repressed (Dimri, et al. 1994; Seshadri, T. et al. 1990; Riabowol, et al. 1992; DeTata, et al. 1993; Hara, et al. 1994) or their binding activity is changed (Dimri, et al. 1994). However, there is a paucity of information about transcription factors as positive regulators of genes involved in inhibition of DNA synthesis and cell proliferation. Indeed a transcription factor specific for or overexpressed in senescent cells, has yet to be identified.
LIM proteins--a new family of transcription regulators
An important new family of proteins, the LIM protein family, has recently been described with roles in developmental and cell growth regulation. The LIM protein family, named for three of the originally identified protein members, lin-11 (Freyd, et al. 1990), isl-1 (Karlsson, et al. 1990), and mec-3 (way, et al. 1988), is defined by the presence of one to three repeats of a 52-residue segment containing two adjacent zinc binding domains separated by a two-residue linker (CX.sub.2 CX.sub.17 HX.sub.2 C)--X.sub.2 --(CX.sub.2 CX.sub.17 CX.sub.2 C/H/D). Although the LIM domain consists of two "zinc finger" domains, a controversy still remains about its DNA binding activity (Sanchez-Garcia, et al. 1994). Several studies indicate that it serves rather as a protein binding interface (Schmeichel, et al. 1994).
The LIM family consists of a variety of proteins with diverse functions and subcellular distributions; it includes transcription factors, protooncogene products and components of adhesion plaques. Based on the protein structure one can categorize the LIM family into three different groups. First, proteins containing a DNA binding homeodomain and a transcription activation domain adjacent to the LIM domains. This subfamily includes transcription factors involved in cell fate determination and differentiation as lin-11, isl-1 and mec-3. The second group, named "LIM-only" proteins, consists of several members that do not contain any additional known functional domains except LIM domains. LIM-only proteins appear to be involved in the regulation of gene activity even if they do not bind to DNA themselves. This group includes among others the protooncogene rhombotin-1, focal adhesion protein zyxin, cysteine-rich intestinal protein CRIP (Sanchez-Garcia, et al. 1994) and three newly discovered proteins with roles in the control of cell proliferation. MLP--muscle LIM protein plays a role in muscle differentiation by driving undifferentiated cells out of the cell cycle, a crucial step for initiation of the differentiation process (Arber, et al.). The protein ril was isolated from a revertant of ras-transformed cells and seems to be involved in the maintenance of normal cell growth (Kiess, et al. 1995). This gene is expressed in a variety of normal differentiated cells but is down-regulated in ras-transformed cells suggesting its function as a negative growth regulator. Another member of the LIM-only group, hic-5 protein was originally isolated from a mouse osteoblastic cell line whose growth was inhibited by TGF-.beta.1 (Shibanuma, et al. 1994). Hic-5 expression is also repressed in ras-transformed fibroblasts as well as in several cell lines established from human tumors. On the other hand the level of its transcript accumulates during senescence in vitro and its overexpression driven by the cytomegalovirus promoter suggests that hic-5 has a cytostatic effect on cell growth (Shibanuma, et al. 1994).
Third, a recently described group of proteins which in addition to LIM domains also contain a protein kinase activity, is represented by two members: Kiz-1, with a role in cell proliferation and neuron differentiation (Bernard, et al. 1994), and LIMK specific for lung tissue (Ohaski, et al.). The specific function for both proteins is not yet known, but there is evidence for their nuclear localization.
Differential gene expression during cellular senescence
Werner syndrome (WS) provides an excellent model for the study of aging because it is a genetically-determined syndrome with features of premature aging (Thweatt, et al. 1993; Goldstein 1978; Salk 1982). The multifaceted pathology that occurs sporadically during aging of normal persons appears almost universally in WS subjects, which becoming manifest earlier and with greater severity. Without exception, HDF derived from WS subjects display a curtailed replicative lifespan and also yield a dominant inhibition of DNA synthesis in hybrid cell fusions with normal yHDF (Salk 1982; Tanaka, et al. 1980). The in vitro observations lead to the prediction that the genes responsible for inhibition of DNA synthesis should be overexpressed in WS cells (Murano, et al. 1991; Goldstein, et al. 1989).


Automatic dispensing apparatus for paper rolls, including a molded housing containing a take-off reel, a cutting blade and a tensioning device in the upper section. A mechanism controls the tensioning and cutting of strips from the roll. A protective cover is hinged to the housing which snaps into place to cover the cutting and dispensing components.

The invention relates to the technical sector of apparatuses dispensing cellulose wadding, creped paper towels and towels of similar materials, especially those intended for wiping the user's hands and toilet paper.
There are a very large number of manual, semi-automatic and automatic dispensing apparatuses which perform the function mentioned above. The Applicant, in particular, has developed several apparatuses of this type with central unreeling, folding of the strip of material in accordion pleats and also as an automatic paper towel dispenser using a cutting device built into a drive drum. All of these apparatuses are currently in use and operate very reliably. The cost price of these various apparatuses varies greatly depending on their construction and they are suited to different market segments.
As part of his own research, the Applicant is interested in designing a new automatic apparatus of which the architecture includes a reduced number of parts so that he can target the market for low-cost paper towel or toilet paper dispensing apparatuses.

Automatic dispensing apparatus for paper towels and toilet paper


A blend of ethylene homopolymers contains at least one blend component having a very low molecular weight and a narrow molecular weight distribution. The blend has surprisingly high density and low hexane extractables. The blend is suitable for the manufacture of a wide variety of plastic goods including extruded goods and molded goods. Plastic film prepared from the blends of this invention have a low Water Vapor Transmission Rate (“WVTR”).

Polyethylene homopolymer which is prepared with a peroxide initiation in a high pressure polymerization process is a widely available item of commerce that is commonly referred to as high pressure/low density polyethylene (or "HPLD"). Such HPLD generally contains a significant amount of long chain branching (or "LCB"). The presence of the LCB reduces the density of the polyethylene. In addition, the presence of the LCB modifies the melt rheology of the polyethylene in a manner which is desirable for many fabrication processes—especially the production of blown film.
It is also known to produce "linear" ethylene homopolymers by the homopolymerization of ethylene with a coordination catalyst (such as a Ziegler Natta or "Z/N" catalyst). The resulting ethylene homopolymers are essentially free of LCB when prepared with a Z/N catalyst. These linear ethylene homopolymers have sharp melting points, which makes them suitable for some injection molding applications. In addition, plastic film which is prepared from linear ethylene homopolymer has high resistance to moisture transmission (or, alternatively stated, a low water vapor transmission rate or low "WVTR"). A review of plastic films having low WVTR is provided in U.S. Pat. No. 6,770,520 (McLeod et al.).
More recently, "linear" ethylene homopolymers have been produced with so-called single site catalysts (such as "metallocene" catalysts or "constrained geometry" catalysts). A review of homopolymers prepared from metallocene catalysts is given in U.S. Pat. No. 6,419,966 (Davis). Similarly, a review of linear ethylene homopolymers prepared with "constrained geometry" catalysts is provided in 2003/008,8021 A1 (Van Dun '03). In addition, the Van Dun disclosure provides a review of resin blends which contain an ethylene homopolymer blend component having a molecular weight distribution of greater than 2.5 (i.e. a blend component which is not prepared with a single site catalyst). Van Dun specifically teaches that "homopolymers derived from typical single site catalysts have the dual disadvantage of, (a) being unable to attain as high a density for a given molecular weight as comparable Ziegler products; and (b) exhibiting a narrow Mw/Mn across the whole molecular weight range.
We have now discovered certain blends of ethylene homopolymers which contain a homopolymer blend component having a polydispersity of less than 2.5, yet the blends have a surprisingly high density and thereby mitigate the disadvantages described by Van Dun '03.