A mailbox bracket assembly (400) for attachment to an existing mailbox door (105) operates to provide a signal when the mailbox door (105) has been opened. The mailbox assembly (400) includes a signal holder arm (101) perpendicularly mounted from the face of a mailbox door (105). A ring section is used for holding a signal ball connected to the signal holder arm while a guard section may be used for blocking objects from inadvertently contacting the signal ball. The signal holder arm (101) extends from the mailbox body such that the position of the signal ball can be easily observed from the rear of the mailbox.

1. Field of the Invention
The present invention relates generally to an apparatus that indicates when mail has been delivered to a mailbox and more particularly to a mailbox delivery indicator assembly that can be viewed from both the front and back of the mailbox.
2. Description of the Related Art
Mailbox indicators that indicate when mail has been deposited in a mailbox are well known in the art. These mail indicators can range in complexity from being very simple to those that require complicated electronics.
U.S. Patent Application Publication No. 2001/0000108 written by Perry and published on Apr. 5, 2001, outlines the use of a mail delivery signal kit, which includes a magnet, which can be mounted on the side or face of a mailbox door. There is also a tethering device which is anchored to a portion of the mailbox, a stopper constructed of a metallic material which will connect to the magnet and which can be attached to one end of the tether and a visual indicator device which can be retained on the tethering device, which is adapted to be stopped by the stopper attached to the tethering device.
U.S. Pat. No. Des. 260,319 issued to Kuntz, Jr. on Aug. 18, 1981, outlines the use of an ornamental design for a mailbox signal. U.S. Pat. No. Des. 356,426 issued to Piatkowski at al. on Mar. 14, 1995, outlines the use of an ornamental design for a mailbox signal. U.S. Pat. No. Des. 457,706 issued to Teichelman on May 21, 2002, outlines the ornamental design for a device for attachment to a mailbox for use in indicating the delivery of mail.
U.S. Pat. No. 2,609,787 issued to Lawson on Sep. 9, 1952, outlines the use of a dual signaling device to assist in mail collection and delivering activities, which are of great benefit to the owner of a mailbox in assuring himself that the mail carrier has been to the mailbox to either pick up mail or to deliver incoming mail, as the case may be.
U.S. Pat. No. 2,707,075 issued to Van Duzer on Apr. 26, 1955, outlines the use of a novel signal member for a mailbox which will automatically move to a clear signaling position visible to the eye both from the front and rear of the mailbox upon the opening of the mailbox door by the mail carrier when he or she deposits mail therein.
U.S. Pat. No. 2,815,167 issued to Bailes et al. on Dec. 3, 1957, outlines the use of a rural mailbox involving a door-actuated signal for indicating a deposit of mail in the mailbox by a mailman.
U.S. Pat. No. 3,426,966 issued to Lay on Feb. 11, 1969, outlines the use of a trough-like member that is structurally integral with the door of a rural mailbox which has its mouth directed upwardly when the door is closed to normally retain an elongated, cylindrical body secured to the mailbox by an elongated transversely flexible member. When the mailbox door is opened by a mail carrier the support member mouth will be tilted downwardly to allow the body to gravitate from the support and to dangle from the transversely flexible member to provide visual indication that the mailbox door has been opened.
U.S. Pat. No. 3,547,070 issued to Schuh on Dec. 15, 1970, outlines the use of a signal attachment for a mailbox having a hinged door with a signal plate attached to one end of a chain, the other end of which is attached to an external mounting of the mailbox. The signal plate is adapted to be manually set in an inconspicuous position and frictionally held between the flange of the door and a sidewall portion of the mailbox.
U.S. Pat. No. 4,138,055 issued to Sherrill on Feb. 6, 1979, outlines the use of a signal device in the form of a coil type spring with an elongated end thereon for fitting under the lip of the door of a rural-type mailbox when the door is in a closed position. Intermediate to the end of the elongated portion is an enlarged portion preferably in the form of a ball to increase the visibility of the device.
U.S. Pat. No. 4,821,953 issued to Poloha on Apr. 19, 1989 outlines the use of a mailbox signaling apparatus for use on both rural-type and residential-type mailboxes. The apparatus includes a suspension unit having a support arm and at least one elongated slot and a signal unit including a signal member attached to the suspension unit, which is provided with an attachment ring that is dimensioned to be selectively received over the support arm and within the slot.
U.S. Pat. No. 5,284,295 issued to Steinfeldt on Feb. 8, 1994, outlines the use of a mailbox delivery signal device with a signal ball of aerodynamic configuration tethered to a support bracket mounted to the door of the mailbox. The support bracket includes a planar support member, which extends perpendicularly to the mailbox door and includes a circular hole having a diameter smaller than the diameter of the signal ball.
U.S. Pat. No. 6,053,404 issued to Jefferson et al. on Apr. 25, 2000, outlines the use of an automatic signaling device to be used with a standard rural mailbox to indicate that the door has been opened when a mail carrier puts mail in the mailbox. The primary components of the device have a signal flag, including a helical spring and a signal plate for attaching to the top end of the spring, a mounting bracket for mounting the helical spring to the door of the mailbox add a retaining bracket attached to the mailbox top.
Great Britain Patent Application No. 2,340,678 granted to Sherrill on Sep. 3, 1960, outlines the use of a signal device in the form of a coil-type spring with an elongated end thereon for fitting under the lip of the door of a rural type mailbox when the door is in the closed position. Intermediate to the end of the elongated portion is an enlarged portion preferably in the form of a ball to increase the visibility of the device. The end of the coil spring opposite the elongated portion has a provision for securing the same to the side of the standard rural type mailbox.
Although this prior art may outline the use of novel and useful devices, what is needed is a removable mailbox delivery indicator that can be observed from the front and the back of a mailbox. Such a mailbox delivery indicator should be versatile and easy to attach to an existing mailbox structure.


This invention addresses the scalability problem of periodic “nanostructured” surface treatments such as those formed by interference lithography. A novel but simple method is described that achieves seamless stitching of nanostructure surface textures at the pattern exposure level. The described tiling approach will enable scaling up of coherent nanostructured surfaces to arbitrary area sizes. Such a large form factor nanotechnology will be essential for fabricating large aperture, coherent diffractive elements. Other applications include high performance, antiglare/antireflection and smudge resistant Motheye treatments for display products such as PDA's, laptop computers, large screen TV's, cockpit canopies, instrument panels, missile and targeting domes, and, more recently, “negative-index” surfaces. Although ideal for seamless stitching of nanometer scale patterns, the technology is broadly applicable to any situation where an arbitrarily large area needs to be seamlessly tiled with a smaller base pattern that has periodic overlap able boundaries.

Nano structured and micro structured surfaces have been investigated for many years in terms of the special functional properties that can be achieved. For example, surfaces made up of many small "protuberances", such as closely and regularly spaced cones, at the micron or sub-micron scale, can exhibit self-cleaning as well as near omni-directional and polarization insensitive anti-reflective properties at optical wavelengths. When features are on the nanometer scale, such so-called "Motheye" nanotextured surface treatments can be ideal anti-glare treatments for display applications. The anti-glare properties can be superior to any other bulk or multi-layered material film approach. A number of examples of such nanometer scale structures or "nanotextures" are illustrated in FIG. 1a. The linear 2-D relief grating is typically used for Bragg grating applications. This particular one was used to realize tight 90 degree bends in integrated optic wave guides1. The negative index structure has the potential for realizing flat lenses, and is currently a popular research topic2. The "Motheye" and SWS ("Subwavelength structures") are both used for anti-reflective applications3, with Motheye being a much more broadband treatment4. The "black hole" structure is used for light trapping applications, but could also be used as a highly efficient field emitter array, such as for backlight or plasma display applications.
Currently, such nanometer scale periodic structures are typically created by using optical beam interference lithography. The issue now is that useful coherent pattern sizes are typically limited to a few inches, creating a barrier to commercial application of these nanotechnologies. What is needed now is a readily scalable coherent nanotextured surface treatment technology. Such a technology could be immediately used in Motheye anti-glare and smudge resistant treatments for the plethora of display devices and windows available in the consumer and industrial markets. These include but are not limited to personal digital assistants, cell phones, portable game devices, laptop computer displays, television screens, and automobile and store-front windows.
An approach to realizing larger form factor nanotextured surfaces at the exposure level can be considered. One series of inventions taught by Hobbes5 and Kelsey, et al.6 describe the use of optical fiber delivery of the exposure beams to increase the coherent interference pattern size and uniformity in the far field recording (exposure) plane. It can be surmised that due to the divergence of the optical beam from an optical fiber, larger pattern size could be achieved by simply increasing the distance between the optical fiber tip and the exposure region. However, this has practical limitations, as larger distances will incur more pointing and vibration sensitivity, as well as wave front phase randomization, all of which will tend to wash out the developed exposure pattern. The other issue is that the exposure intensity is reduced rapidly in a square law sense as the distance is increased, leading to increased exposure times. As an example, an increase in diameter coverage by a factor two incurs an exposure time increase of a factor four. Longer exposure times lead to more washing out of the interference pattern exposure due to vibrations, mechanical, and other drifts.
Another approach to realizing large area micro and nano textured surfaces has been to mechanically stitch together the nanotextured surfaces, either at the master stamp level shown in FIG. 2, or at the product level as shown in FIG. 3. At the master level, many smaller sub-master stamps are bonded together to form a larger master stamp. At the product level, a single smaller master is used to "stamp and repeat" a product film or substrate to cover a larger area. Although there may be some exceptions for certain applications, the vast majority of display applications would require perfect (seamless) stitching, as the human eye is very capable of discerning stitch errors at the microscopic scale. This is due mostly to discontinuous phase boundaries and stitch related defects. Due to practical tolerance issues, such mechanical tiling inherently results in large stitching errors in all 3 dimensions (x, y, and z) when applied to micro and nanometer scale textures. At best, such errors would result in cosmetic and performance reduction in display anti-glare treatments. At worst, such errors make these mechanical approaches completely useless for large area coherent diffraction elements.
A third approach to scaling up these nanotextures combines the optical and mechanical approaches. This approach stitches or otherwise blends together many smaller uniform patterns at the exposure phase to create a larger area coherent pattern. This has been achieved to some degree by researchers at MIT, using what they call "scanning beam interference lithography"7. In that patented work8, large area linear grating patterns were reportedly achieved by scanning the position of a photoresist coated substrate under the fluence of two interfering 1 to 2 mm diameter Gaussian beams. The smaller base interference pattern was thus a simple linear fringe pattern. Positioning of the substrate was reportedly kept on track by feedback from a highly sophisticated optical metrology apparatus. Reportedly, there was some success in fabricating linear gratings (arrays of 400 nm spaced lines) on 300 mm diameter wafers9. However, the apparatus was quite complex, as can be discerned from the lengthy 99 page patent document. This was likely because position control and grating coherence relied on feedback from a fixed reference "fiducial" grating as opposed to locking on to actual previous exposures. Any drift in the fiducial during the scanning process would result in stitch error. Also, note that the 1 mm exposure size would result in very slow process times for large area coverage. Finally, although the 400 nm spacing may be suitable for near infrared applications, it is not sufficient for the less than 200 nm feature sizes required for visible (e.g. display) applications. Also, as the method taught is a scanning approach, it is not amenable to larger area stamp and repeat coherent coverage of more complex 3-D nanotexture patterns, such as Motheye.
McCoy teaches a stitching related invention in a 1995 patent that addresses the intensity profile needed in the tile overlap regions to ensure an overall uniform dosage10. This somewhat obvious method of achieving spatially uniform dosage has also been used by Schattenburg, et al. in their scanning beam interference lithography invention8. There is no reference in McCoy's invention as to how the fine structures of the base pattern would be stitched or mesh aligned. To date, there has been no report of a method by which to perform seamless stitch tiling of nanometer scale patterns to large areas.

Seamless stitching of patterns formed by interference lithography


The present invention can supply a pulse to a pure germanium rod made of germanium so as to significantly increase concentration in a short period of time and shorten dissolving time, and relates to a device for generating and supplying germanium ionic water, which can promote the ionization of germanium.

Many studies on the effects of germanium have been made in Japanese and numerous materials on germanium are present.
However, because germanium is extracted from organic materials to be supplied, it takes much time to extract germanium, and only several grams of germanium can be produced from several tons of organic material even when germanium is extracted from a large amount of organic materials, which increases the price of germanium and makes it difficult for people to purchase germanium.
Meanwhile, because even a small amount of germanium can provide various effects, Lourde spring of France shows many miraculous treatments even though it contains a very small amount of germanium.
Accordingly, because even a small amount of germanium extracted from organic materials is expensive, it is mixed with ferments or yeasts to be sold, and is coupled to ferments or yeasts to be absorbed in the human body.
However, the method of coupling germanium to the ferments or yeasts deteriorates absorption force as compared with ionized germanium ionic water.
Germanium may be extracted even from inorganic materials, and pure germanium may be extracted from germanium ores by heating the ores to the boiling point.
However, even in this case, germanium is coupled to ferments or yeasts to be taken, and powder germanium is supplied to a sauna bath to be effect to skin.
As a result, although germanium in the form of ions contained in mineral water and thermal water is safely taken, the prices of the mineral water and the thermal water are expensive so that ordinary persons cannot easily obtain them practically.
Therefore, a technology of contributing to the health of people by using germanium is necessary.

Device for generating and supplying germanium ionic water


The present invention is a molding compound comprising an unsaturated polyester resin, a filler, a reinforcement material, a crosslinking monomer, a catalyst, and a mold release agent. The compound also may include a thickener and a low profile thermoplastic additive. The mold release agent is a liquid at room temperature and is selected from the group consisting of tertiary alkyl primary amine carboxylates. The present invention further includes a method of manufacturing a molded plastic component using said molding compound.

There are numerous compounds that are used in the production of plastic components. Often, the components are formed using a molding process. To successfully manufacture a molded plastic part, a mold release agent is used in the manufacturing process to permit releasing the finished component from the mold.
One general class of mold release agent is "external" mold release agents. External mold release agents are applied directly to the mold. This procedure increases the manufacturing time and must be repeated every one to five parts. In addition, the mold release agent builds up on the mold, so the mold must be cleaned periodically with a solvent or washing agent. This is costly and time consuming.
A second general class of mold release agent is "internal" mold release agents. Internal mold release agents are added directly into the molding compound. Since they do not have to be continuously reapplied to the mold, internal mold release agents increase productivity and reduce cost.
There are many examples of compounds containing internal mold release agents for manufacturing various types of plastic components. Lee, U.S. Pat. Nos. 4,408,000 and 4,409,351 disclose the use of a fatty acid in the production of thermoplastic parts, which generally are flexible.
Various mold release agents are used in the production of other flexible elastomers, such as polyurethanes and other foams. Haas et al., U.S. Pat. No. 4,753,966 discloses the use of a zinc salt dissolved in an amine liquid as a mold release agent in the production of polyurethanes. Similarly, Meyer et al., U.S. Pat. No. 5,182,034 discloses the use of a metal salt combined with an amine as a mold release agent in the production of polyurethanes.
Mackey, U.S. Pat. No. 5,576,409 discloses the use of a fatty acid amide as a mold release agent. Haylock et al., U.S. Pat. No. 4,551,507 discloses a molding compound including a linear saturated polyester. The mold release agent is a metallic amine carboxylate formed from a metal-containing salt.
One type of molding compound, not described in any of the above patents, is an unsaturated polyester thermosetting molding compound. Such compounds sometimes are referred to as unsaturated polyester resin systems because they all include an unsaturated polyester resin. These compounds are well known in the art. For example, U.S. Pat. Nos. 5,585,439, 5,561,192, 5,449,549, 5445,877, and 5,412,003 each describe various formulations of unsaturated polyester resin systems, which differ from the present invention as described below. They are used in the production of strong, rigid plastic components used as automotive parts, boat hulls, other transportation products, appliances, furniture, computer components, electrical products--anywhere where it is desirable to have a strong, rigid, intricate plastic part manufactured to a stringent tolerance.
Two main types of unsaturated polyester thermosetting molding compounds are known as bulk molding compounds ("BMC") and sheet molding compounds ("SMC"). Such compounds include an unsaturated polyester resin. These resins, with a catalyst, can be cured in a heated mold to form a clear, hard composition. As it cures, the resin has a tendency to shrink slightly, thereby aiding in the release from the mold. The resultant composition, however, is extremely brittle, and therefore not useful in most applications. Therefore, a reinforcement component is added. A filler component, generally a fine ground mineral, is also added to improve appearance and surface characteristics. One common reinforcement material is chopped fiberglass. The resin, glass, and filler can be mixed directly to form a compound having a dough-like consistency, which is then added to a mold. Such a compound is commonly known as a bulk molding compound or BMC. Alternatively, as is known in the art, the molding compound can be formed into a thin sheet, called a sheet molding compound or SMC. The SMC is then molded. Kawakami et al., U.S. Pat. No. 5,445,877, which is incorporated here by reference, provides an example of the making of a sheet molding compound. Both BMCs and SMCs are particularly useful in manufacturing strong, intricate components to stringent tolerances. As, for example, in some of the systems described in the patents referenced above, other components commonly used in BMCs and SMCs include a low profile thermoplastic additive, a crosslinking monomer, and a thickener. Optionally, a pigment also can be included to produce a colored molded part. The use of such additives in unsaturated polyester thermosetting molding compounds, for both BMC and SMC processes, is well known in the art.
When mixed, the resin penetrates or wets the fiberglass reinforcement, thereby dispersing throughout the molding compound. It is desirable to have as much filler as possible in the BMC or SMC, since filler is far less expensive than resin. The addition of filler (and glass), however, inhibits the shrinking that occurs when the resin is molded by itself. BMCs and SMCs, therefore, require that a mold release agent be added. The more filler added, the harder it is to release the finished component, and the more mold release agent that must be used. Likewise, the more intricate the part, the harder it is to release, and the more mold release agent that must be used as well.
The most common mold release agent used in BMC and SMC processes is zinc stearate. It is estimated that zinc stearate is used as the mold release agent in as much as 90% of BMC and SMC processes. Zinc stearate acts by exuding to the surface of the molding compound, thereby contacting the mold and providing lubrication at the mold surface to permit release.
Zinc stearate is a fine, dusty powder, which creates several difficulties. As a powder, zinc stearate is difficult to disperse in the liquid resin. Thus, lumps can form. When lumps of zinc stearate exude to the mold surface, the result is imperfections or pitting on the surface of the finished product. These imperfections interfere with the subsequent treatment of the surface of the part, including interference with the application of vapor deposited metals, laminants, adhesives, paints and the like commonly applied to the surface of molded plastic parts. Depending on the part and its use, the part must be sanded, specially washed, or otherwise treated before adding surface coatings. For example, Uddin, et al., "Laser Surface Engineering of Automotive Components", Plastics Engineering (1997), discloses a method by which SMC automotive parts are treated with a laser to improve surface characteristics. Sometimes, imperfect parts must be discarded. The problems encountered using zinc stearate become more acute as the component becomes more intricate, since more mold release agent must be used.
Powder mold release agents such as zinc stearate also reduce the amount of filler that can be used in that they raise the viscosity of the liquid polyester resins. As a result, powder mold release agents increase the viscosity of the molding compound inhibiting the wetting of the reinforcement by the resin. Thus, more resin and less filler must be used, which increases raw material costs.
To overcome the drawbacks of powder mold release agents like zinc stearate, there has been a need for a liquid mold release agent for use in BMC and SMC processes. State-of-the-art liquid mold release agents are liquid zinc salts and phosphate esters. These materials, however, do not provide sufficient mold release activity for use in the low-shrink resin systems of BMC and SMC processes, and particularly are unsuitable for use in the molding of intricate parts to stringent tolerances. These materials also are very expensive. Thus, for the vast majority of BMC and SMC processes, powder mold release agents such as zinc stearate (and to a lesser extent calcium stearate) remain the primary currently available option.
Two other types of processes for molding with unsaturated polyester thermosetting molding compounds are pultrusion and wet-mat molding processes. In pultrusion, the reinforcement, usually fiberglass, is wheeled off a spool, dipped into a resin mixture, and pulled through a heated die to cure the compound. A mold release agent is used as part of the resin mixture to release the compound from the die. In wet-mat molding, a reinforcement mat is layed on the mold and the molding compound is poured on top of the mat. A mold release agent likewise is used in wet-mat processes. Pultrusion and wet-mat molding compounds differ from BMCs and SMCs partly in that no low profile thermoplastic additive or thickening agent is used. BMCs and SMCs are preferred for more complex molded components, and generally are more difficult to release.
The inventors of the present invention have discovered that certain tertiary alkyl primary amine carboxylates are soluble in and highly compatible with uncured unsaturated polyester resins thereby eliminating many of the disadvantages of zinc stearate and state-of-the-art liquid mold release agents, and are more efficient as mold release agents. The liquid mold release agents of the present invention are particularly advantageous in BMC and SMC processes where release is more difficult to achieve.

Liquid internal mold release agents for unsaturated polyester thermosetting molding compounds


The invention relates to pharmaceutical compositions comprising a corticosteroid and an antioxidant. The invention further relates to methods of treating, preventing, or alleviating the symptoms of and inflammation associated with inflammatory diseases and conditions of the gastrointestinal tract comprising administering the pharmaceutical compositions comprising a corticosteroid and an antioxidant.

Esophageal inflammation disorders are gaining increased recognition in both adults and children. One example is eosinophilic esophagitis (EE or EoE), which is an emerging, and fast-growing disorder characterized by high levels of eosinophils in the esophagus, as well as basal zone hyperplasia. EE (EoE) is thought to be provoked, in at least a subset of patients, by food allergies or airborne allergen exposure (1-5, 44). EE (EoE) diagnosis is often associated with other hypersensitivity disorders, including asthma, rhinitis, and other food and aeroallergen inhalant sensitivities (39-40). Diagnosis is often made, e.g., in young children and depends on the finding of 15 to 20 or more to 24 or more eosinophils per high power field (eos/hpf) within esophageal mucosal biopsies (6-12).
In parallel with other atopic disorders, the incidence of EE (EoE) appears to be increasing (15, 35). The disorder may present with reflux-like symptoms, pain and dysphagia, clinical symptoms similar to the presentation of gastroesophageal reflux disease ("GERD") (42). Symptoms of EE (EoE) include, for example, abdominal pain, chest pain, choking, difficulty swallowing, failure to thrive, nausea, reflux not relieved by standard anti-flux therapy, skin rash or hives, vomiting, and weight loss. In one series, 15% of EE (EoE) patients had concurrent developmental delay (45).
Although EE (EoE) is becoming more frequently diagnosed throughout developing countries (7, 8, 13-16) many aspects of the disease remain unclear including its etiology, natural history and optimal therapy. Symptoms of EE (EoE) often mimic those of GERD and include vomiting, dysphagia, pain and food impaction (8, 14, 17-20). However, treatment of EE (EoE) and GERD differ and it is important to distinguish between them, particularly as untreated EE (EoE) may be associated with esophageal narrowing in 10-30% of cases (14, 18, 20, 21). The overlap of GERD and EE (EoE) symptoms is common; failure to respond to high PPI GERD treatment may be one diagnostic guideline for EE (EoE) (42). The common occurrence regarding misdiagnosis of EE (EoE) for GERD often results in delayed treatment for patients with EE. (42).
Long term systemic steroid therapy can result in significant secondary side effects on growth and bone development. Although treatment with anti-IL-5 monoclonal antibody has been reported to be successful in EE, this therapy is currently not approved for use in children (36).
Current treatments include elimination diets (22, 23), and elemental formulas (2, 24). Identifying true inciting food allergens can be difficult and elemental formulas are often unpalatable, thereby making dietary interventions complicated (1, 22). Improvised puff and swallow techniques may be difficult for patients, especially smaller children, and especially children with developmental delays, to perform efficiently. This may result in a less than effective dose of a topical steroid being delivered to the esophagus.
Corticosteroid compositions for the treatment of EE have been recently developed, see U.S. Pat. Nos. 8,679,545 and 9,050,368. These compositions are designed for oral administration to the esophagus and comprise a therapeutically active amount of a corticosteroid, along with several excipients.
Oxidative degradation of pharmaceuticals is a problem well known to one of ordinary skill in the art. Corticosteroids, such as budesonide, degrade in the presence of oxygen. Specifically, budesonide is known to undergo oxidative degradation with the formation of the undesirable 21-dehydro budesonide (21-DHB) species upon storage. It is therefore highly desirable to provide pharmaceutical formulations in which an oxidation-susceptible corticosteroid active drug ingredient or ingredients are protected against oxidative degradation inherent to prolonged storage. One way of combatting oxidative degradation is through the use of antioxidants. Some anti-oxidants employed in various pharmaceutical formulations may include, inter alia, vitamin E, ascorbic acid, BHT (butylated hydroxytoluene), BHA (butylated hydroxyanisole), and the like.
A common problem observed on drug product appearance is discoloration of pharmaceutical compositions. There are many potential causes for this issue. For example, the source and manufacturing of raw materials, the composition manufacturing process, and the storage process/conditions. Composition discoloration during storage may involve interaction between active, excipients and packaging materials.
Accordingly, there is a need in the art to provide corticosteroid compositions that do not substantially decompose and/or discolor upon storage. There is further a need in the art to provide corticosteroid compositions that are palatable and do not have bitter taste, and do not cause allergic reactions in most patients.


Previously unknown anti-tumor, anti-infectious, immune system modulatory and anti-depressive properties of a family of barbituric acid derivatives are provided herein. Preferred derivatives are 4,6(1H, 5H)-pyrimidinedione, 1,3-dibutyldihydro-2thioxo; and 4,5,6(1H)-pyrimidinetrione, 1,3-dibutyldihydro-2thioxo. These compounds are effective for killing tumor cells, especially carcinoma, lymphoma and leukemia cells; for killing pathogenic organisms, especially viruses; for stimulating T cell formation and for alleviating symptoms of depression and are readily tolerated by the animal being treated.

Current treatment methods for cancer, including radiation therapy, surgery, and chemotherapy, are known to have limited effectiveness. For example, breast cancer annually kills tens of thousands of people in the United States; the numbers are surpassed only by the number of lung cancer deaths. A substantial increase in the number of new cases of prostate cancer has accompanied the aging of the American male population. One estimate suggests that between the years 1990 and 2000, cases of prostate cancer will increase by 90 percent and deaths from prostate cancer will increase by 37 percent (Carter and Coffey, 1990). Prostate cancer currently accounts for 12.3 percent of cancer deaths in men (Gittes, 1991).
Even with the implementation of educational programs designed to curb smoking and eating habits, cancer mortality rates will remain high well into the 21st century. The morbidity and mortality associated with cancer exacts an ever-increasing financial toll on an already overburdened health-care system. Clearly, effective agents that have cytotoxicity and specificity for cancer cells would fill a long and unmet need.
Although vaccines have been enormously successful in preventing many important viral diseases, there is still a pressing need for effective treatment of viral infections. Unfortunately, antiviral chemotherapy has lagged far behind antibiotic treatment for bacterial infections. Until recently, it was very difficult to find drugs that would inhibit viral functions without simultaneously damaging the closely related host cell mechanisms. With the recognizing of viral enzymes and proteins that can serve as molecular targets for drugs (Crumpacker, 1989), antiviral chemotherapy has become a practical reality. Unfortunately, the increasing clinical use of antiviral agents has begun to produce resistant viral strains (Hirsch and Schooley, 1989).
Depression is a serious public health problem with prevalence rates ranging from 5% to 21.3%. These illnesses are present in 3.6% to 7.9% of the population in a one-year period (Angst and Stabl, 1992). In the United States, these numbers translate into 8 million to 36 million adults at risk for depression in their lifetime. Depressed patients are about 20% more likely to attempt suicide and 15% of patients with major depression eventually die by suicide. Although a tremendous improvement in the treatment of these illnesses has been made, approximately 25% of depressed patients have a poor response to any particular antidepressant. Prior to treatment, it is not currently possible to predict which patient will respond. Also, the time for maximal therapeutic benefit to occur is at least one month or longer. Many currently available antidepressants have serious side effects. In view of the aforementioned factors, those of skill in this art have sought new antidepressants that elicit a faster response and have significantly reduced side effects.
The immune response is mediated by two different classes of lymphocytes: T cells, that develop in the thymus, are responsible for cell-mediated immunity; and B cells, that develop in bone marrow or fetal liver, produce antibodies. Thus, T cells are a major component of the immune system and, as such, they play a pivotal role in virtually all aspects of the immune system. The majority of T cells play a regulatory role in immunity, acting either to enhance (helper cells) or suppress (suppressor cells) the response of other white blood cells. T cells are involved in cell-mediated immunity, the production of cytokines, autoimmunity, tolerance, inflammation, and organ rejection. An imbalance of T cell function or their number results in serious disease states. For example, activated T helper cells and mononuclear cells as well as pro-inflammatory cytokines (Menter and Barker, 1991) are involved in psoriasis and arthritis and can be present as severe inflammatory dermatosis in patients with acquired immunodeficiency syndrome (Duvic, M., 1990). The immunodeficiency virus targets T helper cells and this infection causes a severe reduction in helper type T cells by killing them. The resulting imbalance in the number of helper T cells compromises the patient's overall immune system, rendering it ineffective even against common infections. On the other hand, hyperproliferation of T cells results in T cell leukemia. Further, T lymphocytes appear to play a central role in the pathogenesis of asthma (Kline and Hunninghake, 1994). Thus, there is an urgent need for drugs that cause a desirable modulation of T cells for the control of treatment of cancer, AIDS, arthritis, psoriasis and other diseases of the immune system.
The synthesis of barbituric acid starting from hydurilic and diliuric acid was first accomplished by Baeyer (1864). Barbital, a derivative of barbituric acid, was prepared by Conrad and Guthzeit (1882). The pharmacological properties of barbital were later described (Fisher and Mering, 1903; Baeyer, F. & Co., Ger. Pat. 247952, Mar. 04, 1911).
The barbiturates act as nonselective central nervous system depressants and are primarily used as sedative hypnotics and anti-convulsants in subhypnotic doses (Myer and Rollet, 1964). For example, the sodium salts of amobarbital, pentobarbital, phenobarbital, and secobarbital are presently available as prescription drugs. It is important to note that the basic structure common to these drugs, barbituric acid, in itself has no central nervous system activity. Central nervous system activity is obtained by substituting certain alkyl, alkenyl or aryl groups on the pyrimidine ring structure. The role of gamma-aminoisobutyric acid on anticonvulsant activity has been described (Hafeley, 1980).
Certain N-substituted barbituric acids with halogen atoms at C-5 display antiviral properties, including influenza virus (Ger. Offen 2003994, Belg. Pat. 622081). Other compounds such as 5-azidobarbituric acid and phenobarbital-papaverine act as an antispasmolytic (Toth et al., (Alkaloida Vegyeszeti Gyar), Hung, Teljes HU 19767 (Cl. C07D239/62), Apr. 28, 1981; Minelli, 1968; Canellas, Fr. M-3578 (Cl. A61K, C07d), Nov. 08, 1965; Saratikov et al., 1973; Spiridonova and Gol'tsev, 1976). N-arylbarbituric and N-arylthiobarbituric acids act as anti-inflammatory agents (Pol. Pat. 106804; Pol. Pat. 110668; Zawisza et al., 1981; Sladowska, 1977).
Antitumor activity has been reported for 5-formylimidoylbarbituric acid derivatives (Meyer and Althnus, 1979; Kreutzberger, 1978); similar effects have been reported for N-phenyl-thiobarbituric acid under in vivo conditions (Singh and Behl, 1980). For 5,5-disubstituted barbituric acids, activities such as analgesic (Ger. Offen 1 817958; Vida et al., 1975, 1974a, 1974b; Jap. Pat. 20595), antidiabetic (Deshpande and Datta, 1972), antiepileptic (Wirth, 1975), antiinflammatory (Pol. Pat. 76936, Jap. Pat. 6807948), antigenic (Kuroiwa et al., 1980), antithyroid (Astwood et al., 1945), antithrombin (Rehse and Kapp, 1982), cardiotonic (Belonozhko et al., 1966), stimulation of plant growth (USSR Pat. 497006), diuretic (Ger. Offen. 2216619), fungicide and insecticide (Ger. Offen. 2719733; Ger. Offen., 2719777; U.S. Pat. No. 3,919,232; Gorter, 1970), herbicide (Ger. Offen. 2524578), inhibition of gastric secretion (Dinno et al., 1972; Kakemi et al., 1967), hypoglycemic (Shoeb et al., 1967), muscular relaxing (U.S. Pat. No. 3,919,427; U.S. Pat. No. 3,148,189; Bobranski et al., 1961), and hypotensive effects (Toth and Makleit, 1981) have been reported.
Only a few derivatives of thiobarbituric acid were prepared until 1935, when it was discovered that these compounds possess anesthetic properties (Miller et al., 1935; Tabern and Volwiler, 1935; Miller et al., 1936). Derivatives with a thiosemicarbazide group at the C-5 position and phenylhydrazones of 5-monoalkylbarbituric acids display antimicrobial properties (Kamel, 1982; Chemishev, 1979; Chemishev, 1981). The presence of allyl or n-decyl groups also confers antimicrobial properties (Beres et al., 1980; Beres et al., 1974).
Many barbituric acid derivatives such as thiobarbituric acid and its derivatives have also been used in the synthesis of dyes and pigments or intermediates in the preparation of dyes (Gysling, 1949; Schmidt, 1959; Sabata and Rout, 1962). Certain barbituric acid derivatives are photooxidation products of Merocyanine 540, and are reportedly useful as anticancer and antiviral agents (U.S. Pat. No. 5,312,919).
Alloxan has been used as a pretreatment for inhibiting the "take" of transplanted tumor cells (Altman and Spoladore, 1970); and has been used for inducing diabetes (Cherry and Glucksmann, 1971).
The prior art lacks reference to the barbituric acid analogs provided by the present invention as having anti-cancer, anti-pathogenic, immune-stimulating or anti-depressant properties. Because the diseases and other medical conditions that the present invention addresses are severe health problems and because known treatment procedures are not completely satisfactory, persons skilled in the art have searched for improvements.


Disclosed is a method for inducing repair of a joint tissue in a mammal includes the steps of removing a sample of synovial membrane from a joint of the mammal, isolating type B synoviocytes from the membrane to yield a suspension of enriched type B synoviocytes, and introducing the suspension into an injured joint of the mammal as well as medical devices containing enriched synoviocytes and kits for producing such enriched cell populations.

Cartilage is a complex, living tissue that lines the bony surface of joints. It provides shock absorption, enabling the joints to withstand weight bearing through the range of motion needed to perform daily activities as well as athletic endeavors. Articular cartilage damage is the most common type of cartilage damage, and can occur as a result either of injury, degeneration caused by wear and tear, or disease. Individuals with cartilage damage often experience stiffness, decreased range of motion, joint pain and/or swelling in the affected area. The pain may prevent involvement in normal activities. Existing medical treatments may help relieve the symptoms of cartilage damage, but they often do not address the cause of the problem. The demand for therapeutic interventions for the treatment of musculoskeletal damage, especially repair or replacement of damaged cartilage, has increased dramatically in recent years.

Methods and compositions for repairing cartilage


A testing device (10) comprises a storage unit (13), a display unit (11) and a control unit (12). The storage unit (13) is embodied to store messages of at least one test performed on at least one device under test. The control unit (12) is embodied to read in at least one part of the messages, to add them to a selection and to display at least an excerpt of the selection in a view on the display unit (11). The control unit (12) provides a zoom device (16), which, in the selection of messages, controlled by a user by means of an operating device (14), is configured                to increase a number of contained messages in the case of a first user entry, and/or        to reduce a number of contained messages in the case of a second user entry.

Field of the Invention
The invention, according to the various embodiments described herein, relates to a testing device and a test method which are suitable for displaying recorded test results with a zoom display.
Discussion of the Background
A central problem in the analysis of signalling protocol processes is, among the plethora of signalling messages, to identify procedures which do not conform to the specifications in a rapid and targeted manner. In many cases of error in this context, it is not sufficient to search for messages with an incorrect content or incorrect transmission/reception time, but complex dependencies between protocol messages must be recognized.
Signalling protocols in message networks are tested by means of network simulators. In this context, in the case of a test, a given sequence of signalling procedures is stimulated by the network simulator. Accordingly, always starting with a well-defined starting condition, the reaction of the device under test (DUT=device under test) is registered and checked against the defined, set behaviour according to the set specification. In this context, the overall message exchange between the network simulator and the device under test is recorded on the various protocol layers in a log file with timestamps. The display and evaluation of this log file is implemented after the completion of the test case with the assistance of special applications (Log File Viewer). To search for errors, the user can analyse the protocol process in a sequential manner, filter the content of the log file according to freely selectable criteria and search for given messages.

Testing device and a test method with zoom display


An imaging device comprising comprises a matrix of pixels, at least one data conductor connected to several pixels of the matrix, organized row-wise and successively transporting signals delivered by respectively the pixels of the row and an electronic current generator supplying several pixels, each of the pixels comprising: a transistor delivering at the node of the pixel, the signal delivered by the pixel considered and wherein can flow a bias current from the current generator, and a first electronic switch connecting the node of the pixel to the data conductor associated with this pixel as a function of a selection signal of the pixel. Each of the pixels comprises a second electronic switch, distinct from the first electronic switch, joined to the node of the pixel, the current arising from the generator to be made to flow in the transistor as a function of the selection signal for the pixel.

This type of device comprises a large number of photosensitive points called pixels generally organized as a matrix or strip array. In a detector, a pixel represents the elementary sensitive element of the detector. Each pixel converts the electromagnetic radiation to which it is subjected into an electrical signal. The electrical signals arising from the various pixels are collected during a phase of reading the matrix and then digitized so as to be able to be processed and stored to form an image. The pixels are formed of a photosensitive zone delivering a current of electric charges as a function of the flux of photons which it receives, and of an electronic circuit for processing this current. The photosensitive zone generally comprises a photosensitive element, or photodetector, which may for example be a photodiode, a photoresistor or a phototransistor. Photosensitive matrices of large dimensions which may possess several million pixels are found.
The radiation detector can be used for the imaging of ionizing radiations, and notably X rays or γ rays, in the medical sector or that of nondestructive testing in the industrial sector, for the detection of radiological images. The photosensitive elements make it possible to detect a visible or near-visible electromagnetic radiation. These elements are hardly, if at all, sensitive to the radiation incident on the detector. Use is then frequently made of a radiation converter called a scintillator which converts the incident radiation, for example X-ray radiation, into a radiation in a band of wavelengths to which the photosensitive elements present in the pixels are sensitive. An alternative consists in producing the photosensitive element from another material carrying out the direct conversion of the X-ray radiation into electric charges. This is the case for example for matrices in which a first pixellated substrate made of Cadmium Telluride (CdTe) is connected pixel by pixel to a CMOS reading circuit which therefore no longer possesses the detection function.
It is known to produce an electronic processing circuit by means of a voltage follower making it possible to read the current of charges accumulated in the photosensitive element. A current source ensures the power supply for the pixel during its reading. An exemplary imaging device thus produced is represented in FIG. 1.
This figure schematically presents a matrix of two rows and two columns to simplify understanding. Four pixels are formed, each at the intersection of a row and column. Of course the real matrices are generally much larger.
Each pixel comprises a photosensitive zone represented here by a photodiode D and an electronic processing circuit formed of three transistors T1, T2 and T3. In the figure, the labels of the photodiode D and of the three transistors are followed by two coordinates (i,j) that can take the rank of the row for i and the rank of the column for j.
The pixels of one and the same column or more generally of one and the same row share a transistor T4 and a reading circuit S situated at the column end. The transistor T4 and the reading circuit S are linked to the pixels of the column by means of a conductor Col. The pixels of one and the same row are joined to four conductors conveying signals Phi_line, Vdd, V_ran and Phi_ran making it possible to control each of the rows of pixels.
The transistor T1 makes it possible to reinitialize the voltage of the cathode of the photodiode, to the voltage V_ran, during a phase of reinitializing the matrix during which the control signal Phi_ran is active.
After reinitialization, the illumination received by the photodiode D causes the potential of its cathode to decrease during an image capture phase.
This image capture phase is followed by a reading phase during which the potential of the photodiode D is read. Accordingly, the transistor T3 is turned on, the latter therefore having a role as switch, by virtue of the command Phi_line applied to its gate.
The transistor T2 operates as follower, and the transistor T4 operates as current source. The transistors T2 and T4 then form a voltage-follower stage which copies the voltage present on the cathode of the photodiode D, and reproduces it, to within a shift, on the input of the reading circuit S at the column end. To carry out its copyover, the transistor T2 requires a bias current flowing in its drain and its source. This current is imposed by a current generator formed by a transistor T4 common to several pixels. In the example represented, the transistor T4 is common to a column of pixels.
The voltage Vs present at the input of the reading circuit S can be expressed:Vs=Vp−VT−K  (1)
Where Vp is the voltage of the cathode of the photodiode, VT is the threshold voltage of the transistor T2, and K is a constant related inter alia to the value of the current delivered by the transistor T4.
The voltages V_ran and Vdd are often identical.
The phase Phi_line of a row n of a matrix is often the same as the phase Phi_ran of the preceding row n−1. In this case the integration period for the signal upstream of the follower lasts, for row n−1, from the end of the addressing of row n, until the addressing of row n−1 at the following image. The reinitialization and reading phases are therefore different for each row. One speaks of circular addressing of the rows, well known in the literature by the name "rolling shutter".
The addressing circuits (generally shift registers) generating the control signals Phi_line and Phi_ran are not represented in the figure and are disposed at the row end.
The various outputs of the reading circuits S of the various columns are thereafter multiplexed in a register, not represented in the figure, so as to obtain a video signal of a row.
It is also possible to use just a single current-source transistor T4, for the whole of the matrix, on condition it is switched successively onto the various columns, in tandem with the reading of these same columns.
In practice, each column Col exhibits a lineal resistance represented in the form of a resistance R_pix for each pixel. Relation (1) is correct only at the level of the output node of the pixel, that is to say at the level of the source of the transistor T2. But when this voltage is situated at the end of the columns, on the input of the reading circuit S, it is marred by an ohmic shift related to the resistance of the transistor T3 and to the number n of pixels separating the pixel selected from the reading circuit S along the column Col. The number n corresponds to the rank of the pixel read in the matrix. More precisely, the voltage Vs is expressed:Vs=Vp−VT−K−I×(R(T3)+n×R_pix)  (2)
The ohmic shift is troublesome since it depends on the rank of the pixels read and it therefore introduces a variable skew into the reading of the voltages Vp of the photodiodes.
A solution consists in decreasing the lineal resistance value R_pix of the columns Col by increasing the width of tracks forming the column Col conductors. This solution nonetheless presents several drawbacks.
The increase in width of the tracks uses some surface area of the substrate on which the matrix is produced, and therefore reduces the useful surface area in each pixel for photodetection.
The increase in width of the tracks also increases their electrical capacitance. Now, the voltage of the columns changes upon the addressing of each new row, since it represents at each row the illumination of the corresponding pixels. Increasing the electrical capacitance of the column therefore makes it necessary to feed (or to extract) further charges upon each change of row. This increase in the current increases the ohmic drop, thereby reducing the effect initially sought. Ultimately, this is manifested by an increase in consumption, or by a limitation of the reading speed.
The structure of such a pixel with three transistors therefore finds a limit in respect of matrices of large dimensions in which the column capacitances and the column resistances are significant. These matrices cannot be read rapidly.
Another solution consists in replacing the current sources, common to a column, with current sources disposed in each pixel by means of an additional transistor such as for example described in patent application No. WO2009/043887.
The output column Col conductor then no longer has the role of conveying the bias current for the follower stage. It is used only as a device for observing the output voltage of the pixel. It works at zero current, outside of the current transients necessary at each row transition to establish the new voltage value. At the end of these transients, the current on the column conductors being zero, the voltage is the same over the whole of the length of these columns, and in particular the voltage at the column end does indeed represent, with no shift, the voltage of the pixel. The lineal resistance R_pix no longer therefore causes any voltage drop along the column conductor.
This solution nonetheless has the defect, by introducing a current-source transistor into each pixel, of requiring the corresponding control voltages on the gate and the source of this transistor.
Distribution of the gate voltage over a matrix is done without any ohmic drop, since there is no corresponding consumption. But the distribution of the source voltage undergoes ohmic drops since it must generate the bias current for the follower transistor T2.
The source voltage of the additional transistor varies from one pixel to the next as a function of the lineal resistance of the conductor conveying this voltage. The potential difference between gate and source defines the value of the current delivered by these transistors to bias each follower transistor T2. These variations in bias current from one pixel to another therefore create, as in the pixel with three transistors, dispersions on the output signals.
It is possible to alleviate this drawback by keeping the potential difference between source and drain of the additional transistor constant for all the pixels. For this purpose, a voltage drop equal to that which exists on the sources of the current-source transistors is created on their gates, by connecting them to a lateral resistive bar which reproduces the same voltage drop as that which exists on the sources of the additional transistors as described in patent application FR 2 921 788. The resistive bar is linked to all the gates of the additional transistors of a column and is supplied between two voltages, high and low, at the ends of the bar.
This solution operates well, but is fairly complex to put in place and to pilot, since it requires two voltages, high and low (Vg1, Vg2) for biasing the lateral resistive bar.
Another solution for circumventing the problem of ohmic drop has for example been proposed in patent application EP 1 416 722 A1. This solution consists in displacing the current source onto the opposite edge of the matrix, with respect to the edge on which the reading circuits S are situated.
The bias current for the pixel goes from the selected pixel up to the current source, and therefore creates an ohmic drop in the part of the column conductor above the selected pixel. But the lower part, connected to the reading circuit S, is not traversed by any current, and does not therefore undergo any ohmic drop. The lower end of the pixel is therefore properly representative of the voltage of the pixel.
However, this solution exhibits several limitations. It is necessary to have the space required to produce the source at the top of the column. And in the case where several matrices have to be assembled or abutted, for example in fours, so as ultimately to obtain a sensitive area four times as large, then the top of the column is situated at the limit of the desired smallest possible abutment zone. It is therefore not desirable to place in this abutment zone components not belonging to the actual pixels. This would distance the sensitive parts of the elementary matrices, thus creating a dead line in the final image at the level of the abutment.
Moreover, the voltage drop between the addressed pixel and the current source must not be too large, so that the current-source transistor remains in saturated mode, and properly fulfills its current-source function. And as described previously, if the width of the column is increased in order to reduce this voltage drop, this will increase consumption.

Imaging device with zero ohmic drop in a data conductor

Commissariat A L'Energie Atomique ET Aux Energies Alternatives


A PIN active pixel sensor array including self aligned encapsulated electrodes and a method for forming the same the method including forming an electrically conductive layer over a substrate; forming a first doped semiconducting layer over the conductive layer; photolithographically patterning and etching through a thickness portion of the first doped semiconducting layer and conductive layer to expose the substrate to form a plurality of spaced apart electrodes having an upper portion comprising the first doped semiconducting layer; blanket depositing a second doped semiconducting layer to cover the spaced apart electrodes including the exposed substrate; and, etching through at least a thickness portion of the second doped semiconducting layer.

A conventional imaging sensor array is formed from a plurality of photosensitive pixel elements typically arranged in an array forming rows and columns. As the size of pixel elements has decreased and associated sensor circuitry has been integrated into multi-level integrated circuit devices, the photosensitivity of the pixel elements including photodiodes has correspondingly required improvement to counteract the effects of increased light scattering, low u-lens gain, and low fill factor. For example the fill factor, as is commonly referred to in the art, is the ratio of a photodetector area divided by the pixel area. For example, a photodetector typically includes an array of photosensitive elements, often referred to as pixels, including spacing between the pixel array rows and columns which are not active in photosensing. A higher fill factor is one method to increase photosensitivity.
Recently elevated PIN photodiodes with high fill factors have been used to increase photosensitivity. One problem with elevated PIN photodiodes has been related to vertical leakage current that occurs at metal and intrinsic amorphous silicon forming Schottky junction interfaces. For example, typically intrinsic amorphous silicon sensor material, also referred to as an I-layer creates charge carriers upon illumination with light through a P+ doped amorphous silicon portion (layer). The charge carriers are then selectively collected by a Schottky diode electrode formed of an N+ doped amorphous silicon portion over a metal portion. The metal portion collects the charge from the N+ doped amorphous silicon portion for transport to detector or readout electronics, for example including CMOS transistors.
During the formation of the of the photodiode sensors, prior art processes have frequently left metal portions of the Schottky diode electrode in contact with the I-layer. As a result, vertical leakage current upon application of a bias voltage to the Schottky diode electrode degraded charge collection and photosensitivity of the PIN photodiodes. For example, under reverse bias conditions, a leakage current resulting from contact injection occurs at an interface of the intrinsic amorphous silicon layer (I-layer) and the metal portion or back contact.
While several PIN sensor elements have been disclosed in the prior art, the teachings as disclosed in Theil et al., in U.S. Pat. No. 6,018,187 and Mei et al., in U.S. Pat. No. 6,288,435 are incorporated herein by reference.
For example, in Mei et al., an approach to address the vertical leakage current problem has been to extend the N+ amorphous silicon layer, in a mushroom shaped contact electrode to cover metal/I-layer interfaces. One problem with such structures has been vertical leakage current due to contact of the active layer (I-layer) with the conductive portion of the electrode.
Another problem with the method of the prior art in forming thin film PIN photodiodes is that mushroom shaped contacts increase the electrode size which thereby increases an active pixel size. The increased size of the electrode including the extension of the N+ doped amorphous silicon layer to encapsulate the metal portion has the offsetting effect of decreasing the fill factor thereby lowering photosensitivity. In addition, the method is time consuming and costly in terms of throughput and processing costs in that at least two photolithographic patterning steps must be performed to form the extended N+ doped amorphous silicon layer.
There is therefore a need in the image sensor art for an improved PIN sensor including rear electrode formation to improve a thin film PIN photodiode fill factor while avoiding the formation of Schottky junctions producing a vertical leakage current.
It is therefore an object of the invention to provide an improved PIN sensor to improve a thin film PIN photodiode fill factor including a rear electrode and method of forming the same while avoiding the formation of Schottky junctions producing a vertical leakage current, in addition to overcoming other deficiencies and shortcomings of the prior art.

Self-aligned rear electrode for diode array element

Taiwan Semiconductor Manufacturing Co., Ltd.


Described herein are systems and methods for cryogenic fluid delivery. The systems may include a pressure vessel containing a cryogenic fluid formed of liquid and vapor that is connected to a use device via a withdrawal line. The withdrawal line connects to the cryogenic fluid in the pressure vessel via two routes, a liquid tube and a vapor line. The vapor line may include a back-pressure regulator that opens the vapor line depending on pressure in the system. The withdrawal line may include a pressure relief valve that exerts pressure on the liquid tube. A bypass line may connect the withdrawal line to the liquid tube. The bypass line has a check valve that permits free flow of cryogen from the withdrawal line to the liquid tube via the bypass line while prohibiting cryogen flow from the pressure vessel through the bypass line. The methods employ the systems described herein.

Liquid Natural Gas (LNG) vehicle pressure vessels are widely used in heavy duty trucking operations. U.S. Pat. No. 5,421,161 describes an improved cryogenic fuel tank system. The system is particularly useful in horizontal cryogenic tanks (i.e. pressure vessels), such as those containing low-density fluids like LNG. However, while the system of the '161 patent works quite well for reducing pressure inside a pressure vessel through an economizer circuit, it actually limits the pressure vessel's ability to build pressure in mobile applications because it limits the rate of backflow of product to the vessel.
In view of the foregoing, there is a need for an improved cryogenic fuel pressure vessel system that is particularly suited for horizontal fuel pressure vessels.

Economizer biasing valve for cryogenic fluids


A unified assembly of a mounting cup and valve stem assembly for aerosol containers. The mounting cup contains a flat central portion having an inner section extending downward from its periphery. An outer section extends upward from the lower edge of the inner section and abuts the inner section. The inner and outer sections constitute the lower wall. The outer section extends above the flat central portion and ends in a channel which can fit onto the bead of an aerosol container. The flat central portion has at least one hole through it. The valve stem assembly contains a flat circular upper piece having holes corresponding to those in the mounting cup. The holes are the open top ends of chambers for springs and plungers. Valve stems are below the chamber. The lower wall of the mounting cup is crimped to hold the mounting cup to the valve stem assembly.

1) Field of the Invention
This invention relates to unified mounting cups and valve stem assemblies for aerosol containers. More particularly, this invention relates to unified mounting cups and valve stem assemblies suitable for use with multi-valve aerosol containers.
2) Description of the Related Art
Aerosol containers are widely used to package a variety of fluid materials, both liquid and powdered particulate products. Typically, the product and a propellant are confined within the container at above atmospheric pressure and the product is released from the container by manually opening a dispensing valve to cause the pressure within the container to deliver the product through the valve and connecting conduits to a discharge orifice.
In aerosol containers of the related art, the dispensing valve, crimped to a mounting cup having a sealing gasket, is normally mounted in a top opening of the container, which opening is defined by a component commonly referred to as the "bead" of the container opening. The mounting cup includes a central pedestal portion for crimping the dispensing valve, a profile portion extending outward from the pedestal portion, which profile portion merges into an upwardly extending body portion, the body portion merging into a channel portion terminating in a skirt portion, which channel is configured to receive the bead portion of the container opening. The sealing gasket normally is disposed within the channel portion and in many gasket configurations extends downward along a part of the body portion. After the sealing gasket is disposed onto the mounting cup, the cup is positioned onto the container and the cup is crimped to the container. The crimping operation is well-known to those skilled in the aerosol container art.
In a conventional form of aerosol valve assembly, a vertically acting aerosol valve is opened to release product in the aerosol container by downwardly depressing an actuator attached to the top of the upstanding stem of the aerosol valve body. When the actuator is released, the valve is closed by a spring acting upwardly against the valve plunger. The valve stem has an upwardly extending discharge passage, a groove extending about the stem periphery, a lateral valve orifice (one or more) extending through the stem wall into the groove, and a stem-encircling sealing gasket for fitting into the groove and closing the lateral orifice except when the valve is actuated to depress the stem lateral orifice below the gasket.
Multi-valve aerosol dispensers embodying the above features are known in the art, as see U.S. Pat. No. 7,036,685 issued to Green May 2, 2006, which is incorporated herein by reference.
A prior disclosure of conventional one-inch mounting cups containing single and multiple valve stems is made in U.S. Pat. No. 6,736,288 issued to Green May 18, 2004, which is incorporated herein by reference.

Unified mounting cup and valve stem assembly


According to an example aspect of the present invention, there is provided a method comprising, transmitting by a wireless device, during a first phase, a first probe signal associated with a user and receiving a reflected version of the first probe signal, transmitting by the wireless device, during the first phase, the reflected version of the first probe signal to a ground truth classifier, transmitting by the wireless device, during a second phase, a second probe signal associated with the user and receiving a reflected version of the second probe signal and transmitting by the wireless device, during the second phase, the reflected version of the second probe signal to a trusted apparatus.

Radio signals, for example on frequencies between 2.4 GHz and 5 GHz, reflect off human bodies, thereby enabling Radio Frequency, RF, -based imaging, such as user identification and pose estimation. RF-based imaging provides various advantages. For instance, RF-based imaging provides advantages related to privacy as a resolution of RF-based imaging is inherently low and thus, faces of users typically cannot be identified. Security of RF-based imaging may be an issue though, e.g., if an unauthorized party is able to steal sensor data related to reflections of RF signals associated with a user, the unauthorized party may be able to recreate imaging information related to the user, such as an image, a pose or a location of the user. There is therefore a need to provide improved methods, apparatuses and computer programs which enable secure RF-based imaging.


This timepiece has a winding stem (1) with three axial positions and two first connecting wheels (9, 10) which are superposed and pivoted about two respective stationary axes, and mesh with the winding pinion (2), two second connecting wheels (11, 14) meshing respectively with the said first connecting wheels (9, 10), two bars, namely a winding bar (8) and a connecting bar (15), which are pivoted coaxially to the respective axes of pivoting (8b, 15a) of the said second connecting wheels (11, 14), one carrying a reverser pinion (12) and the other a correcting pinion (16), meshing with the said respective second connecting wheels (11, 14), means (7, 17, 15xe2x80x2c, 15xe2x80x2d) of connection between each of the two bars (8, 15) and the said pull-out piece (6) to act on the said bars (8, 15) according to the axial position of the said winding stem (1) so as selectively to place the said reverser pinion (12) in engagement with a winding ratchet wheel (13) and the said correcting pinion (16) in engagement with the said member (19, 20) for indicating a function derived from time.

This application claims priority of EP Application No. 00810384.8 filed May 5, 2000.
Not Applicable.
1. Field of the Invention
The present invention relates to a timepiece with a mechanism for winding and for correcting at least two indicator members, comprising a winding stem, a pull-out piece engaged, on the one hand, with this winding stem and, on the other hand, with a jumper spring defining three axial positions of the said winding stem, corresponding to those for winding, for correcting at least one indicator member indicating a function derived from time, and for setting the correct time, the said winding stem carrying a winding pinion and a castle wheel engaged with a bar acted upon by a spring and connected to the said pull-out piece to selectively place the said castle wheel in engagement with the said winding pinion and with a minute-wheel geartrain when the said winding stem is in the extreme positions.
2. Description of the Prior Art
Such mechanisms are known and are used in all mechanism timepieces that comprise an indicator indicating a function derived from time, such as the days of the month, the days of the week, the phases of the moon, and the various time zones in particular.
Control of these various functions entails axial movement of the control rod, generally known as the winding stem, into three positions, the first position, that is to say the one in which the winding stem occupies the position in which it is pushed towards the centre of the movement is the usual winding position, one of the two remaining positions is the one for correcting the date or similar derived function, while the other of the remaining positions is the one for setting the correct time.
In general, the winding pinion pivoted on the winding stem is used only for winding when placed in engagement with the castle wheel and the latter is moved axially into the other two positions to come into engagement with a connecting wheel connected alternately to the geartrain for setting the correct time and to the geartrain for setting the date or any other derived function. When the timepiece indicates the days of the month and the days of the week, use is generally made of a bar which, in the correcting position, can move, depending on the direction in which the winding stem is turned, alternately between two angular positions so as to bring the correcting pinion into engagement with the day-of-the-month indicator or with the day-of-the-week indicator. Such correcting mechanisms are described, for example, in GB 1,234,004, in FR 2,169,861 or alternatively in CH 571,734.
One of the problems posed by operating three functions stems from the fact that the winding pinion is used only for winding, which means that the castle wheel has to control two functions. Now, the castle wheel with its two sets of teeth around the edge is the member which, by being moved axially over a portion of non-circular section of the stem makes it possible, in one axial position, to drive the winding pinion in one direction of rotation and, in the other axial position, to come into engagement with the minute-wheel geartrain in order to set the time. This member can thus fulfil two rather than three functions, which means that in three-function mechanisms, instead of coming directly into engagement with the minute-wheel geartrain, the castle wheel comes into engagement with a geartrain designed to be able to be connected alternately with the minute-wheel geartrain or with a geartrain for correcting the day-of-the-month indicator or indicator of some other function derived from time.
In order to switch from one correcting function to the other in these three-function mechanisms, it is therefore necessary to resort to somewhat complicated devices that employ systems involving connecting wheels, reverser pinions and multiple clutches, which may present problems of penetration of the sets of teeth in one another and therefore problems of wear and of bracing.
One of the problems encountered in such mechanisms is that of the winding stem becoming axially jammed when passing from one position to another, if the corrector malfunctions during the change in axial position, which jamming is brought about by the way in which the corrector is operated. Another problem is that of inadvertent correction brought about when the winding stem is moved from one axial position to another.
The object of the present invention is to overcome the aforementioned drawbacks, at least in part.
To this end, a subject of the present invention is a timepiece with a mechanism for winding and for correcting at least two indicator members as defined in claim 1.
Unlike mechanisms of the prior art, the winding pinion controls two functions in succession: winding and correcting the indicator of a function derived from time, so that when the castle wheel is moved axially along the winding stem, it is in order to come into direct engagement with the minute-wheel geartrain. In consequence, the castle wheel of the mechanism for winding, for setting the time and for correcting some other indication derived from time, operates like a conventional castle wheel, remaining in engagement with the winding pinion in two of the three axial positions of the winding stem.
As to the winding pinion, instead of being in engagement with the edge teeth of the winding button, it is simultaneously in engagement with two fixed connecting wheels, themselves meshing with two respective second connecting wheels coaxial with two respective bars which, simply by moving these bars, allow the winding stem to be connected alternately with the winding ratchet wheel or with the corrector for correcting the indication derived from time. Finally, the castle wheel moves only upon the change to the position for setting the time, as in a bar and pull-out-piece conventional two-function winder.
Advantageously, in order to avoid the winding stem becoming jammed as it passes from the winding position to the position for correcting the indication derived from time, the castle wheel is moved into an intermediate axial position so that its teeth are not in engagement either with the winding pinion or with the minute-wheel geartrain.
This arrangement makes it possible to avoid the winding stem becoming jammed axially as it moves from the winding position to the position for correcting the indication derived from time. This operation causes the winding bar to move from the winding position into the position which disengages a reverser pinion carried by this bar and initially in engagement with the winder ratchet subjected, in one direction of rotation, to the tension of the mainspring and immobilized in the other direction of rotation by a retaining pawl. This arrangement also makes it possible, when the winding stem is moved in the opposite direction, to avoid inadvertently correcting the indicator that indicates a function derived from time.

Timepiece with a mechanism for winding and for correcting at least two indicator members


A magnet is integrally formed with a mirror surface for reflecting off a laser beam. A torsion spring holds the magnet thereon. The torsion spring is made of a shape-memory alloy. A coil generates an alternating magnetic field so as to oscillate the magnet about the torsion spring. The oscillating magnet scans the light beam.

1. Field of the Invention
The present invention relates to an optical scanner used in a laser printer, a bar code reader, a laser scan micrometer, and the like.
2. Description of the Related Art
U.S. Pat. Nos. 5,221,933 and 5,280,377 disclose an optical scanner provided with a mirror-mounted magnet. The optical scanner is also provided with a coil for generating an alternating magnetic field.
According to U.S. Pat. No. 5,221,933, a driving magnet 62 is connected via an adhesive to a mirror 60 as shown in FIG. 1. The mirror 60 is supported by a pair of leaf sprints 70 via magnet inserts 78. A driving coil 64 is provided surrounding the driving magnet 62. When an alternating current flows in the coil 64, an alternating magnetic field is produced around the coil 64. The alternating magnetic field applies a torque to the driving magnet 62, whereby the magnet 62 and the mirror 60 attached to the magnet 62 angularly oscillate in a non-resonant mode. Light reflected off the mirror 60 is scanned in a direction orthogonal to the axis about which the mirror 60 oscillates.


To produce a filtering material for adsorptively capturing very fine particles such as fungus, pollen, virus, bacteria or the like at a high efficiency, an aqueous treatment solution is first prepared by dissolving porous apatite particles of 0.5 to 40% by weight, preferably, 0.5 to 30% by weight and a water soluble glucan of 0.5 to 15% by weight in water. A sheet-shaped raw material is then coated with the treatment solution with the aid of a rotating drum of which part is always dipped in the treatment solution, and thereafter, the sheet-shaped raw material having the treatment solution coated thereon is dried. Alternatively, an aqueous treatment solution prepared by dissolving only a water soluble glucan of 0.5 to 25% by weight in water may be substituted for the aforementioned aqueous treatment solution. In this case, after a sheet-shaped raw material is coated with the treatment solution, porous apatite particles are deposited on the sheet-shaped raw material by employing a dispersing process or a spraying process before the treatment solution coated on the sheet-shaped raw material is kept still wet. Subsequently, the sheet-shaped raw material having the treatment solution coated thereon and the porous apatite particles deposited thereon is dried.

1. Field of the Invention
The present invention relates generally to a method of producing a filtering material practically employable in various application fields including a sanitary material such as a mask or the like, a deodoring filter to be incorporated in various kinds of deodoring units and a foodstuff packing material having sterilizing and deodoring functions. More particularly, the present invention relates to a method of producing a filtering material having a capability of adsorptively capturing very fine infectious or antigenous particles such as virus, bacteria or the like.
2. Description of the Related Art
The applicant common to the present invention has already proposed a method of producing a filtering material capable of adsorptively capturing virus under Japanese Patent Application Nos. 278487/1990 and 29301/1991. An outline of each of the prior inventions is such that a predetermined quantity of porous apatite particles and a predetermined quantity of water soluble glucan are dispersively dissolved in water to prepare an aqueous treatment solution, a sheet-shaped raw material is dipped in the treatment solution or it is coated with the same by employing a spraying process so as to allow it to be impregnated with the treatment solution, and thereafter, the sheet-shaped raw material having the treatment solution coated thereon is dried.
In spite of the already proposed methods of which excellent filtering property has been proven by repeated practical use, the applicant additionally conducted a series of development works for a filtering material having a more excellent filtering property and has reached the present invention.

Method of producing a filtering material


The present invention provides improved methods and compositions for the generation of transgenic non-human animals. The present invention permits the introduction of exogenous nucleic acid sequences into the genome of unfertilized eggs (e.g., pre-maturation oocytes and pre-fertilization oocytes) by microinjection of infectious retrovirus into the perivitelline space of the egg. The methods of the present invention provide an increased efficiency of production of transgenic animals with a reduced rate of generating animals which are mosaic for the presence of the transgene.

The ability to alter the genetic make-up of animals, such as domesticated mammals such as cows, pigs and sheep, allows a number of commercial applications. These applications include the production of animals which express large quantities of exogenous proteins in an easily harvested form (e.g., expression into the milk), the production of animals which are resistant to infection by specific microorganisms and the production of animals having enhanced growth rates or reproductive performance. Animals which contain exogenous DNA sequences in their genome are referred to as transgenic animals.
The most widely used method for the production of transgenic animals is the microinjection of DNA into the pronuclei of fertilized embryos. This method is efficient for the production of transgenic mice but is much less efficient for the production of transgenic animals using large mammals such as cows and sheep. For example, it has been reported that 1,000 to 2,000 bovine embryos at the pronuclear stage must be microinjected to produce a single transgenic cow at an estimated cost of more than $500,000 (Wall et al., J. Cell. Biochem. 49:113 [1992]). Furthermore, microinjection of pronuclei is more difficult when embryos from domestic livestock (e.g., cattle, sheep, pigs) is employed as the pronuclei are often obscured by yolk material. While techniques for the visualization of the pronuclei are known (i.e., centrifugation of the embryo to sediment the yolk), the injection of pronuclei is an invasive technique which requires a high degree of operator skill.
Alternative methods for the production include the infection of embryos with retroviruses or with retroviral vectors. Infection of both pre- and post-implantation mouse embryos with either wild-type or recombinant retroviruses has been reported (Janenich, Proc. Natl. Acad. Sci. USA 73:1260 [1976]; Janenich et al., Cell 24:519 [1981]; Stuhlmann et al., Proc. Natl. Acad. Sci. USA 81:7151 [1984]; Jahner et al., Proc. Natl. Acad. Sci. USA 82:6927 [1985]; Van der Putten et al., Proc. Natl. Acad. Sci. USA 82:6148–6152 [1985]; Stewart et al., EMBO J. 6:383–388 [1987]). The resulting transgenic animals are typically mosaic for the transgene since incorporation occurs only in a subset of cells which form the transgenic animal. The consequences of mosaic incorporation of retroviral sequences (i.e., the transgene) include lack of transmission of the transgene to progeny due to failure of the retrovirus to integrate into the germ line, difficulty in detecting the presence of viral sequences in the founder mice in those cases where the infected cell contributes to only a small part of the fetus and difficulty in assessing the effect of the genes carried on the retrovirus.
In addition to the production of mosaic founder animals, infection of embryos with retrovirus (which is typically performed using embryos at the 8 cell stage or later) often results in the production of founder animals containing multiple copies of the retroviral provirus at different positions in the genome which generally will segregate in the offspring. Infection of early mouse embryos by co-culturing early embryos with cells producing retroviruses requires enzymatic treatment to remove the zona pellucida (Hogan et al., In Manipulating the Mouse Embryo: A Laboratory Manual, 2nd Ed., Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y., [1994], pp. 251–252). In contrast to mouse embryos, bovine embryos dissociate when removed from the zona pellucida. Therefore, infection protocols which remove the zona pellucida cannot be employed for the production of transgenic cattle or other animals whose embryos dissociate or suffer a significant decrease in viability upon removal of the zona pellucida (e.g., ovine embryos).
An alternative means for infecting embryos with retroviruses is the injection of virus or virus-producing cells into the blastocoele of mouse embryos (Jahner, D. et al., Nature 298:623 [1982]). As is the case for infection of eight cell stage embryos, most of the founders produced by injection into the blastocoele will be mosaic. The introduction of transgenes into the germline of mice has been reported using intrauterine retroviral infection of the midgestation mouse embryo (Jahner et al., supra [1982]). This technique suffers from a low efficiency of generation of transgenic animals and in addition produces animals which are mosaic for the transgene.
Infection of bovine and ovine embryos with retroviruses or retroviral vectors to create transgenic animals has been reported. These protocols involve the micro-injection of retroviral particles or growth arrested (i.e., mitomycin C-treated) cells which shed retroviral particles into the perivitelline space of fertilized eggs or early embryos (PCT International Application WO 90/08832 [1990]; and Haskell and Bowen, Mol. Reprod. Dev., 40:386 [19951). PCT International Application WO 90/08832 describes the injection of wild-type feline leukemia virus B into the perivitelline space of sheep embryos at the 2 to 8 cell stage. Fetuses derived from injected embryos were shown to contain multiple sites of integration. The efficiency of producing transgenic sheep was low (efficiency is defined as the number of transgenics produced compared to the number of embryos manipulated); only 4.2% of the injected embryos were found to be transgenic. Haskell and Bowen (supra) describe the micro-injection of mitomycin C-treated cells producing retrovirus into the perivitelline space of 1 to 4 cell bovine embryos. The use of virus-producing cells precludes the delivery of a controlled amount of viral particles per embryo. The resulting fetuses contained between 2 and 12 proviruses and were shown to be mosaic for proviral integration sites, the presence of provirus, or both. The efficiency of producing transgenic bovine embryos was low; only 7% of the injected embryos were found to be transgenic.
The art needs improved methods for the production of transgenic animals, particularly for the production of transgenics using large domestic livestock animals. The ideal method would be simple to perform and less invasive than pronuclear injection, efficient, would produce mosaic transgenic founder animals at a low frequency and would result in the integration of a defined number of copies of the introduced sequences into the genome of the transgenic animal.

This patent is subject to a terminal disclaimer.


A front-edge paper feeding device is applicable for automatically conveying a stack of cardboards one by one. During operation, the stack of cardboards is placed on a grid plate, and a control element is provided for controlling the grid plate to elevate and descend reciprocally. When the grid plate elevates, the cardboards are separated from a conveyor wheel. When the grid plate descends, the conveyor wheel is exposed, such that the conveyor wheel is in contact with the cardboard. A servomotor is provided for controlling intermittent rotations of the transmission shaft while driving the conveyor wheel, so that the conveyor wheel drives the cardboard to move in order to convey and output the cardboard smoothly.

At present, corrugated cardboards are used extensively in our daily life for carrying, protecting, transporting, and storing objects. In the manufacture of corrugated cardboards, folding, preheating, corrugated molding, gluing, cooling, line pressing, trimming, cutting and stacking processes are used for making the corrugated cardboards, so that the corrugated cardboards can further be manufactured to produce cartons, paperboards and various forms of products for different purposes.
In a conventional front-edge paper feeding device of a corrugated carton machine, the paper feeding operation includes the steps of: continuously sucking and pulling the bottom corrugated cardboard of a stack of corrugated cardboards from a hollow platform at the front of the machine by an air extraction device, so that the corrugated cardboards are placed equidistantly with one another on the platform and slightly higher than a plurality of conveyor belts on the surface of the platform, and then transmitting each conveyor belt by a clutch mechanism to rub, drive and send the bottom corrugated cardboard into a transfer roller set in the machine, and then extracting the bottom corrugated cardboard of the stack of corrugated cardboards by the transfer roller set, and finally feeding the corrugated cardboard into the corrugated carton machine to carry out other manufacturing processes such as creasing, slotting, printing, and cutting processes.
However, the air extraction device has air extraction passages interconnected with each hollow position of the platform, so that the flow of the air extraction is distributed uncertainly all over the platform due to the size and area of the corrugated cardboard, and idle suctions occur frequently and cause unnecessary waste of energy. In this situation, the air extraction power must be increased. In addition, the extraction force varies with the area and idle suction position of the corrugated cardboard, so that different pressures may be exerted on the corrugated cardboard and its contact surface with each conveyor belt, and uneven wearing may occur. Therefore, the corrugated cardboard bears a conveying force with uneven frictions and results in a skew feed and affects the quality of transferring the corrugated cardboard from the transfer roller set for manufacturing operations at a later stage.
In view of the aforementioned problems and drawbacks of the prior art, the inventor based on years of experience in the related industry to conduct extensive researches and experiments, and finally designed and develop a front-edge paper feeding device in accordance with the present invention to provide quick delivery and smooth separation of paper materials and facilitate the operations in a later manufacturing process.