Improved adhesion of thermal barrier coatings to nonmetallic substrates using a dense layer of ceramic on an underlying nonmetallic substrate that includes at least one oxidizable component. The improved adhesion occurs because the application of the dense ceramic layer forms a diffusion barrier for oxygen. This diffusion barrier prevents the oxidizable component of the substrate from decomposing. The present invention applies ceramic by a process that deposits a relatively thick and dense ceramic layer on the underlying substrate. The formation of the dense layer of ceramic avoids the problem of void formation associated with ceramic formation by most prior art thermal decomposition processes. The formation of voids has been associated with premature spalling of thermal barrier layers and other protective layers applied to substrates.

The present invention generally relates to composite materials and specifically to the protection of silicon carbide containing materials in hot, oxidizing environments such as ceramic matrix composites (CMC""s) in which at least one of the components of the CMC""s includes silicon carbide (SiC). Silicon carbide containing materials have not been used in hot oxidizing atmospheres such as the combustor or turbine portion gas turbine engines for various components because of problems with oxidation of the SiC.
SiC has a tendency to oxidize, the SiC being converted into silica (SiO2) and CO2 at elevated temperatures. Even when coatings are utilized for protection of the underlying SiC in hot, oxidizing environments, there is a tendency for oxygen to diffuse through the coating to oxidize the SiC to form carbon monoxide, CO, or carbon dioxide, CO2, and silica. This transformation also produces voids that exist in one of several places. The voids may appear in the external coating and/or in the interfacial silica scale formed by the transformation. The voids can also exist at the interfaces between the silica scale and the substrate. Of course the voids can also form tat the interface between the silica scale and the external coating. The voids are undesirable as thy decrease the environmental protection provided by any external coatings. Not only do the voids break down the SiC, which can adversely affect the mechanical properties of the CMC composite, which are designed around the mechanical properties of its system components, but also the voids can provide a path of least resistance that permits the continued inward diffusion of oxygen to promote further deterioration of the SiC composite. The voids can aggregate during the course of operation at high temperatures and can reduce the life of the external coating by promoting spallation of the applied coating.
Various systems are available for protection of carbon/carbon composites such as silicon carbide systems, from oxidation. One of these systems is a complex coating that includes an outer layer of a first coating comprising titanium diboride, colloidal silica and an intermetallic compound applied over a thin, primary coating of boronated silicon carbide as set forth in U.S. Pat. No. 5,536,574 to Carter. The invention improves the oxidation protection of a carbon/carbon composite wherein the secondary coating of diboride, colloidal silica and an intermetallic compound applied over the primary coating melts to form a crystalline glass ceramic coating. While the coatings improved oxidation protection to the substrates at temperatures of about 2400xc2x0 F., the temperature capabilities and times at temperature of the crystalline glass ceramic coating formed by melting at temperatures in the range of 2200-2400xc2x0 F., is limited by its melting temperature.
Other approaches such as set forth in U.S. Pat. No. 5,776,550 to Disam et al. (""550 Patent) and U.S. Pat. No. 5,741,596 to Skowronski et al. (""596 Patent) improve oxidation protection of metal substrates by utilizing variations of the glass/ceramic coatings formed of metallic silicides. The ""550 patent utilizes a boron-containing silicide to form a low melting oxide mixtures that have improved crack-healing properties as compared to pure SiO2. The ""596 Patent teaches the use of multi-layered coatings, the last of which is a thin layer of SiO2 applied by the sol-gel process.
Approaches for protecting CMC composites against oxidation are described in U.S. Pat. No. 5,246,736 to Goujard et al. This process utilizes a ternary Sixe2x80x94Bxe2x80x94C system to form a borosilicate glass and avoids the drawbacks encountered when there are superposed layers of precursors for boron-based glass and for silica-based glass.
Yet another approach is set forth in Thebault et al. in U.S. Pat. No. 5,622,751 which utilizes a coating of a mixture of non-oxide refractory ceramic, refractory ceramic and a polymer to form a commingled network.
What is needed is a system that can be readily applied to a substrate of a ceramic matrix composite material that forms a barrier to diffusion of oxygen that is both easy to apply to the substrate and adherent to the substrate. The diffusion barrier must be easy to apply and be capable of maintaining its resistance to oxygen diffusion, even at temperatures of up to 3000xc2x0 F. Ideally, the material should be also improve the adherence of thermal barrier coatings to the CMC substrate so that the component to which it is applied can be used in environments that experience even higher temperatures.
Improved adhesion of thermal barrier coatings to nonmetallic substrates is provided by applying a dense ceramic layer on the underlying nonmetallic substrate that includes at least one oxidizable component by appropriate methods that permits the formation of a dense ceramic coatings such as silica. The improved adhesion occurs because the application of the dense ceramic layer inhibits the penetration of oxygen by forming a diffusion barrier. This protection is required for articles such as gas turbine components designed to operate in high temperature, oxidizing atmospheres such as is found in the combustor portion of gas turbine engines and in sections of the engine downstream from the combustor portion. While silica has been used to protect substrates, it usually has been used in multi-layer systems or has been applied by application of SiC followed by thermal decomposition to yield silica and associated voids. The present invention applies silica by a process that deposits a relatively thick and dense layer of silica on the underlying CMC composite. The formation of the dense layer of silica avoids the problem of void formation associated with silica formation by thermal decomposition. Thus, the silica coating formed will not only provide protection of the underlying substrate from decomposition due to oxidation at elevated temperatures, but also will provide improved adhesion for coatings such as thermal barrier coatings applied over the component to increase its ability to perform at elevated temperatures.
An advantage of the present invention is that it forms a protective, diffusion barrier layer over the CMC composite that prevents the diffusion of oxygen through it. This prevents the deterioration of any materials present in the CMC that are subject to degradation by oxidation.
Another advantage of the present invention is directly related to the ability of the dense silica layer to inhibit form a diffusion layer. Since oxygen cannot penetrate the silica layer, the formation of voids at the interface or below the interface is prevented. As void formation is related to spalling of layers above the voids, particularly as the voids coalesce.
Another advantage is that the silica can form a strong bond with most non-metallic engineering materials that can be used as structural components in the hot portions of gas turbine engines. The typical thermal barrier coatings that overly these structural components to improve their thermal response also form are capable of forming good bonds with the dense silica.
Other features and advantages of the present invention will be apparent from the following more detailed description of the preferred embodiment, taken in conjunction with the accompanying drawings which illustrate, by way of example, the principles of the invention.

Method for improving the performance of oxidizable ceramic materials in oxidizing environments


A film-like materials of resin manufacturing method for producing a film-like material made of a resin by rolling a thermoplastic resin material containing a thermoplastic resin using a molding apparatus comprising first rotation molding members composed of a pair of rollers, wherein the method is characterized in that the rotation molding is carried out under the conditions satisfying the following inequalities of the line contact pressure P (kN/m) applied to the thermoplastic resin, the peripheral velocity R (m/sec) of the rollers of the first rotation molding members, and the thickness H (m) of the film-like material made of the resin after rolling. (formula 1) 3×9.8≦P (formula 2) 3×9.8×10−6≦P/(R/H2)≦2×9.8×10−5, wherein the reference character P denotes the line contact pressure P (kN/m), the reference character R denotes the peripheral velocity (m/sec) of the rotation molding members, and the reference character H denotes the thickness (m) of the film-like material made of the resin after rolling.

1. Field of the Invention
The present invention relates to a manufacturing method of a film-like material made of a resin, more particularly, to a manufacturing method of a film-like material made of a thermoplastic resin with excellent appearance. The invention also relates to a crystalline thermoplastic resin film with a high elastic modulus and a high strength and a manufacturing method of the same.
Conventionally the following methods have been known as a manufacturing method of a film made of a thermoplastic resin; a T-die molding method for extruding a melted resin into a thin film-like shape out of a slit die with a wide width, so-called T-die and an inflation molding method for molding a cylindrical film by extruding a resin into a cylindrical shape out of a die slit of such as a ring die and the like while cooling the resin and keeping it flat by two plates. Also, a calendar molding method (Japanese Provisional Publication No. 10-296766(A)) using a plurality of calendar rolls has been known.
However, the above-described methods have the following problems.    (1) If a resin with a high molecular weight, a resin with a high melt viscosity, or a resin deficient in melt elongation is used, defects such as voids are easy to be formed and the appearance of the film becomes inferior and especially in the case of production of a film with a film thickness of 200 μm, the appearance was considerably inferior.    (2) In the case of the above-described calendar molding method, when melted resin composition is passed through a pair of calendar rolls while forming a bank, the molding is carried out while making the peripheral velocities of both heated rolls different, so that the surface of the obtained film is not necessarily smooth and beautiful and the surface inevitably becomes roughened and also from such a point, subsequently, it is impossible to produce a film with a sufficiently high film thickness precision.    (3) In the case of the T-die molding method and the inflation molding method, the film thickness precision of the molded film is insufficient and especially, in the case of producing a film from a resin with a high melt viscosity and a hardly formable resin with a low melt elongation degree, the film thickness precision is significantly deteriorated and these methods cannot be said a proper molding method as a manufacturing method of a film or a sheet required to provide a high film thickness precision.
The invention has been developed taking the above-described circumferences into consideration and a object of the invention is to provide a manufacturing method capable of obtaining a film-like material made of resin and having excellent appearance.
In consideration of the above-described problems of the conventional techniques, another object of the invention is to provide a method for producing a film-like material made of a resin and having a high film thickness precision even in the case of using a resin material with a high melt viscosity and a low melt elongation degree, for example, a thermoplastic resin containing a long molecular chain polyolefin.
As a film of a crystalline thermoplastic resin, various kinds of films have been known and employed for practical uses. As a technology of providing a crystalline thermoplastic resin film with a high elastic modulus, for example, Japanese Patent Application Laid-Open No. 7-173302 discloses a manufacturing method of a polypropylene sheet using a polypropylene mixed with a crystallization nucleating agent.
Although the polypropylene sheet produced by the above-described known technique is provided with a higher elastic modulus than that of polypropylene sheets produced ever before and improved secondary processibility such as the vacuum molding property, these improvements cannot be said sufficient yet.
The other purpose of the invention is to provide a crystalline thermoplastic resin film with a high elastic modulus and a high strength and a manufacturing method for the same.
2. Description of the Related Art

Manufacturing method of film-like materials of resin and film-like materials of resin


An integrated circuit carrier with conductive rings and a semiconductor device integrated with the carrier are proposed. A plurality of concave structures are formed on the conductive rings at predetermined positions above which a plurality of wires traverse, the wires being provided for electrically connecting the carrier to a semiconductor chip mounted on the carrier. Therefore, an insulating effect between the wires and the conductive rings is provided to prevent short circuit, so as to maintain the performance of the semiconductor device.

Ball Grid Array (BGA) technology is an advanced type of semiconductor packaging technology, which is characterized by the use of a substrate mounted with a semiconductor chip on a front side thereof and implanted with a grid array of solder balls on a back side thereof, wherein the solder balls serve as input/output (I/O) connections to bond and electrically connect the semiconductor package to an external printed circuit board (PCB). This arrangement allows relatively more I/O connections to be accommodated on the same unit area of a chip carrier such as the substrate to comply with the requirement of a highly integrated semiconductor chip.
In order to make good use of the intended performances of the semiconductor chip in the BGA semiconductor package that is electrically connected to the external PCB via the solder balls, the circuit design of the chip carrier or substrate should be divided for different functions such that power supply, grounding and signal transmission.
U.S. Pat. No. 5,581,122 discloses a substrate provided with conductive rings such as a ground ring and a power ring and signal fingers thereon. Referring to FIG. 1 of a semiconductor device 1, a ground ring 111, a power ring 112 and a plurality of signal fingers 113 are arranged around a chip mounting area 110 on an upper surface of a substrate 11. A semiconductor chip 12 having a plurality of ground pads 121, power pads 122 and signal pads 123 is mounted on the chip mounting area 110. A wire-bonding process is performed to form a plurality of ground wires 131, power wires 132 and signal wires 133. The ground wires 131 electrically connect the ground pads 121 of the chip 12 to the ground ring 111 of the substrate 11; the power wires 132 electrically connect the power pads 122 of the chip 12 to the power ring 112 of the substrate 11; and the signal wires 133 electrically connect the signal pads 123 of the chip 12 to the signal fingers 113 of the substrate 11. Then, an encapsulant (not shown) is formed and encapsulates the upper surface of the substrate. A plurality of solder balls (not shown) are mounted to a lower surface of the substrate and electrically connected to the ground ring 111, the power ring 112 or the signal fingers 113 via corresponding conductive traces (not shown) provided on the lower surface of the substrate. When the semiconductor device 1 is bonded and electrically connected to an external device by the solder balls, the electrical quality of the chip 12 can be sustained via the ground ring 111 and the power ring 112, and the chip 12 can transmit electric charges through the ground ring 111 and is supplied with power through the power ring 112 during operation. Other related prior arts include U.S. Pat. Nos. 5,686,699 and 5,801,440.
Furthermore, along with the development of electronic devices made more compact in size and more complicated in structure, semiconductor package structures have been developed toward a chip size scale. Therefore, how to arrange high-density circuits in gradually reduced space of an integrated circuit carrier becomes am important issue in the associated industry. Accordingly, the integrated circuit carrier is generally designed to shorten a pitch distance between the adjacent conductive rings such as ground ring and power ring and a spaced distance between the conductive rings and the signal fingers, such that surface area of the integrated circuit carrier would be less occupied to thereby provide more area for arranging high-density circuits and facilitate the size miniaturization of the semiconductor device.
Referring to FIG. 2, when the pitch distance between the adjacent conductive rings or the spaced distance between the conductive rings and the signal fingers are reduced to be less than about 200 μm, a solder mask 20 for covering surface circuits of an integrated circuit carrier 2 cannot be precisely applied between the conductive rings 21 due to fabrication limitations, thereby making the area between the conductive rings 21 on the integrated circuit carrier 2 exposed. Then, when a semiconductor chip 22 is mounted on the integrated circuit carrier 2 and electrically connected to the integrated circuit carrier 2 via a plurality of wires 23, the wires 23 connected to the conductive ring 21 located relatively more far from the chip 22 have larger length and loop height and usually traverse above the other conductive ring 21 located closer to the chip 22. These wires 23 may easily sag and come into contact with the exposed underlying conductive ring 21 not covered by the solder mask 20, thereby leading to short circuit between the sagging wires 23 and the contacted conductive ring 21 and affecting reliability of the fabrication processes.
Referring to FIG. 3, in accordance with the foregoing problems, U.S. Pat. No. 6,449,169 discloses a solder mask 30 being applied between adjacent conductive rings 31 such as ground ring and power ring to support any sagging wires 33 and prevent the conductive rings 31 from short circuit. However, as discussed above that due to size miniaturization of the semiconductor device, the pitch distance between the adjacent conductive rings is reduced as much as possible and is not sufficient to accommodate a solder mask. Also the solder mask cannot be reliably provided between the conductive rings due to fabrication limitations, such that the patent is not well practicable in reality.
Therefore, considering the size miniaturization of semiconductor devices, the problem to be solved here is to provide an integrated circuit carrier and a semiconductor device with the carrier, which can prevent wires from short circuit with conductive rings due to undesirable contact between the wires and the conductive rings and provide industrial practicability.

Integrated circuit carrier with conductive rings and semiconductor device integrated with the carrier

Siliconware Precision Industries Co., Ltd.


This invention provides for a protein of the TGF-β superfamily in which the cysteine involved in the normal formation of homodimers is changed to another amino acid. These mutant proteins, as monomers, display higher bone morphogenetic activity than the wild-type protein dimers. Also provided is a method for producing and isolating these monomers by plasmid driven expression in various host systems including E. coli. In addition, the invention discloses the use of an agent containing purified monomers in preventing and treating diseases and problems affecting bone and/or cartilage.

(1) Field of the Invention
The present invention relates to a monomer protein having an amino acid sequence belonging to TGF-β superfamily, of which cysteine related to a dimer formation of a protein has been replaced with another amino acid. Moreover, the present invention relates to a method for preparing said monomer protein in a large amount and with a high purity by using Escherichia coli transformed with a plasmid containing a DNA sequence that can express said monomer protein. Furthermore, the present invention relates to an agent containing said monomer protein for preventing and treating a disease affecting bone and/or cartilage.
(2) Description of the Related Art
Currently, there are known estrogen, calcitonin, vitamin D3, its derivatives and derivatives of bisphosphonic acid as preventive or therapeutic agents for bone diseases. Recently, it has been reported that a bone morphogenetic activity is found in a series of a bone morphogenetic protein (hereinafter referred to as "BMP") belonging to TGF-β superfamily, from BMP-2 to BMP-14.
Moreover, it has been reported that a protein named GDF-5 or human MP52 has a bone morphogenetic activity (WO93/16099, WO95/04819, WO94/15949 and Nature Vol. 368, 1994, p. 639–643). It is considered that mature human MP52 is a protein having 120 amino acid residues starting with alanine at an N-terminal, and its amino acid sequence has been described in these patent applications.
These proteins exist as a homodimer having a single disulfide bond in nature. On the contrary, the manufacture of their recombinant protein is carried out using their homodimers or heterodimers to yield a protein showing the activity. For example, human MP52 has been reported in the publication of unexamined application, JP 031098/97. Meanwhile, there are two types named type I receptor and type II receptor in the receptors of TGF-β superfamily. Intercellular signal transmission via receptors of TGF-β superfamily containing these bone morphogenetic proteins (dimers) requires simultaneous combination of these proteins to both type I and type II receptors, and it is considered that a polymer is formed by gathering of two or more dimers to do intercellular signal transmission (Bone, Vol. 19, 1996, p. 569–574). It has been considered that for polymer formation it is important that the protein should be a dimer. The activity in a monomer has not yet been found. Moreover, preparation for these monomer recombinants has not yet been carried out.

Monomer protein with bone morphogenetic activity and medicinal agent containing the same for preventing and treating diseases of cartilage and bone

Biopharm Gesellschaft zur biotechnologischen Entwicklung von Pharmaka mbH


The present invention provides a drawing apparatus for performing drawing on a substrate with a plurality of charged particle beams, comprising a blanker array including first and second groups, each of which includes at least one blanker, a deflector configured to deflect the plurality of charged particle beams to scan the plurality of charged particle beams on the substrate, and a controller configured to respectively supply first and second control signals to the first and second groups at first and second timings, wherein the first and second groups are respectively arranged at such relative positions that a positional difference between respective drawing regions thereof, due to a difference between the first and second timings, in a scanning direction of the deflector is compensated for.

1. Field of the Invention
The present invention relates to a drawing apparatus, and a method of manufacturing an article.
2. Description of the Related Art
Along with miniaturization and higher integration of circuit patterns in semiconductor integration circuits, a drawing apparatus which draws a pattern on a substrate using a plurality of charged particle beams (electron beams) has received a lot of attention. The drawing apparatus that uses the plurality of charged particle beams is described in, for example, WO 2009/147202. In recent years, the drawing apparatus is required to improve a throughput, and the number of charged particle beams is dramatically increased to meet such requirement.
In such drawing apparatus, for example, a plurality of blankers required to independently blank the plurality of charged particle beams are arranged, and signal lines required to supply control signals which controls the blankers are respectively connected to the blankers. For this reason, when the number of charged particle beams is increased, a large number of signal lines are used accordingly, and it is difficult to connect the large number of signal lines to the plurality of blankers. Hence, non-patent literature 1 has proposed a drawing apparatus which employs an active-matrix driving system for supplying control signals to respective blankers at different timings so as to increase a data volume to be transmitted per signal line and to reduce the number of signal lines.
In the drawing apparatus described in non-patent literature 1, the respective blankers control charged particle beams at different timings. On the other hand, a deflector required to scan the charged particle beams on a substrate simultaneously deflects a plurality of charged particle beams. For this reason, positions on the substrate, which are deviated in the scanning direction, may be unwantedly irradiated with the plurality of charged particle beams which are to strike on an identical position with respect to the scanning direction according to timing differences controlled by the blankers.    Non-Patent Literature 1: M. J. Wieland et. al., "Throughput enhancement technique for MAPPER maskless lithography", Proc. of SPIE, USA, SPIE, 2010, Vol. 7637, 76371Z

Drawing apparatus, and method of manufacturing article


Systems and methods are disclosed for selecting target objects within digital images utilizing a multi-modal object selection neural network trained to accommodate multiple input modalities. In particular, in one or more embodiments, the disclosed systems and methods generate a trained neural network based on training digital images and training indicators corresponding to various input modalities. Moreover, one or more embodiments of the disclosed systems and methods utilize a trained neural network and iterative user inputs corresponding to different input modalities to select target objects in digital images. Specifically, the disclosed systems and methods can transform user inputs into distance maps that can be utilized in conjunction with color channels and a trained neural network to identify pixels that reflect the target object.

Recent years have seen a rapid proliferation in the use of digital visual media. Indeed, with advancements in digital cameras, smartphones, and other technology, the ability to capture, access, and utilize digital images and video has steadily increased. Accordingly, engineers have made significant developments in digital object selection systems that capture, manage, and edit digital images. For example, some conventional object selection systems can identify and select objects portrayed within digital images.
Although some conventional systems can identify and select digital objects, these systems have a variety of problems and shortcomings. For example, some common digital object selection systems detect user tracing of an area within a digital image and select pixels within the traced area. Although such systems allow a user to select pixels in a digital image, they are often rough, over-inclusive, under-inclusive, and/or time consuming. Indeed, conventional systems that rely upon manual tracing commonly fail to provide sufficient precision to accurately select objects. Moreover, in order to achieve increased accuracy, such systems often require an exorbitant amount of time and user interactions to trace an object in a digital image.
Similarly, some common digital object selection systems are trained to identify pixels corresponding to common object classes. For example, some common digital systems are trained to identify and select pixels corresponding to dogs, cats, or other object classes. Although such systems are capable of identifying and selecting common objects, they are limited by the particular classifications with which they are trained. Because the number and type of object classes in the world is so vast, such common digital object selection systems can severely limit the ability to identify, select, and modify objects in digital visual media. Moreover, because such common systems identify pixels corresponding to a particular object type, they often have difficulty distinguishing between multiple objects belonging to the same class.
In addition, some conventional digital object selection systems are tied to fixed types of user input. For example, some conventional digital object systems can identify digital objects based on rigid input of area tracing inputs. By specializing on a specific type of user input, these conventional systems reduce flexibility and accuracy, inasmuch as a particular type of user input may only be effective at identifying target objects in specific circumstances (e.g., tracing may only be efficient for easily identifiable and tracable shapes).
These and other problems exist with regard to identifying objects in digital visual media.

Utilizing interactive deep learning to select objects in digital visual media


According to one embodiment of the present invention, a method and a device for improving communication quality in a mobile communication network are provided, and the method further comprises the steps of transmitting downlink packets for IP-based voice traffic to a terminal in a radio link unacknowledged mode (RLC UM) and storing at least one packet among the downlink packets for retransmission. In addition, the present invention provides a communication method and device of a target base station for retransmitting the stored packet to the terminal. Furthermore, the present invention provides a method and a device of a terminal that receives a packet from the target base station.

The mobile communication system has been developed for a user to communicate on the move. With the rapid advance of technologies, the mobile communication system has evolved to the level of being capable of providing a high speed data communication service as well as a voice telephony service. Recently, Long Term Evolution-Advanced (LTE-A), as one of the next-generation mobile communication standards, has been underway in the 3rd Generation Partnership Project (3GPP). LTE-A aims at commercial deployment around a 2010 timeframe, and its standardization is almost complete with various technologies for accomplishing data rates higher than those of the current systems.
In line with the completion of the LTE standardization, recent studies are focused on the LTE-Advanced (LTE-A) for improving data rates with the adoption of several new techniques for the legacy LTE system. The term "LTE system" as used herein may be construed to include the legacy LTE system and the LTE-A system.
LTE is a data only communication standard, which means that it does not support voice transmission. Nevertheless, the increased data rate or bandwidth make it possible to support voice calls over the Internet, so called VoLTE. This is a technology for communicating compressed voice information over data networks such as Voice over IP (VoIP) services provided by Internet telephony (070) service providers and mobile messenger applications. However, this technology is different from VoIP because the data rate is adjusted according to the network condition and also a predetermined communication quality is guaranteed that will maintain the connection in any situation.
Although the sound quality in voice calls is important, guaranteeing the connection is more important. A robust connection requires giving up sound quality; a high sound quality requires giving up the robustness of the connection. Even though a connection may be disconnected during a communication service such as web surfing, the user may not feel significant discomfort. However, if the connection quality drops during a voice service, the voice data is lost or the connection is disconnected, which causes discomfort to the user. There is therefore a need of a technology capable of protecting against degradation of voice service quality.

Method and device for improving communication quality in mobile communication network


A controlled release antihyperglycemic tablet that does not contain an expanding polymer and comprising a core containing the antihyperglycemic drug, a semipermeable membrane coating the core and at least one passageway in the membrane.

The present invention relates to controlled release unit dose formulations containing an antihyperglycemic drug. More specifically, the present invention relates to an oral dosage form comprising a biguanide such as metformin or buformin or a pharmaceutically acceptable salt thereof such as metformin hydrochloride or the metformin salts described in U.S. Pat. Nos. 3,957,853 and 4,080,472 which are incorporated herein by reference.
In the prior art, many techniques have been used to provide controlled and extended-release pharmaceutical dosage forms in order to maintain therapeutic serum levels of medicaments and to minimize the effects of missed doses of drugs caused by a lack of patient compliance.
In the prior art are extended release tablets which have an osmotically active drug core surrounded by a semipermeable membrane. These tablets function by allowing a fluid such as gastric or intestinal fluid to permeate the coating membrane and dissolve the active ingredient so it can be released through a passageway in the coating membrane or if the active ingredient is insoluble in the permeating fluid, pushed through the passageway by an expanding agent such as a hydrogel. Some representative examples of these osmotic tablet systems can be found in U.S. Pat. Nos. 3,845,770, 3,916,899, 4,034,758, 4,077,407 and 4,783,337. U.S. Pat. No. 3,952,741 teaches an osmotic device wherein the active agent is released from a core surrounded by a semipermeable membrane only after sufficient pressure has developed within the membrane to burst or rupture the membrane at a weak portion of the membrane.
The basic osmotic device described in the above cited patents have been refined over time in an effort to provide greater control of the release of the active ingredient. For example U.S. Pat. Nos. 4,777,049 and 4,851,229 describe an osmotic dosage form comprising a semipermeable wall surrounding a core. The core contains an active ingredient and a modulating agent wherein the modulating agent causes the active ingredient to be released through a passageway in the semipermeable membrane in a pulsed manner. Further refinements have included modifications to the semipermeable membrane surrounding the active core such as varying the proportions of the components that form the membrane, i.e U.S. Pat. Nos. 5,178,867, 4,587,117 and 4,522,625 or increasing the number of coatings surrounding the active core, i.e U.S. Pat. Nos. 5,650,170 and 4,892,739.
Although vast amounts of research has been performed on controlled or sustained release compositions and in particular on osmotic dosage forms, very little research has been performed in the area of controlled or sustained release compositions that employ antihyperglycemic drugs.
The limited work on controlled or sustained release formulations that employ antihyperglycemic drugs such as metformin hydrochloride has been limited to the combination of the antihyperglycemic drug and an expanding or gelling agent to control the release of the drug from the dosage form. This limited research is exemplified by the teachings of WO 96/08243 and by the GLUCOPHAGE(copyright) product which is a commercially available product from Bristol-Myers Squibb Co. containing metformin HCl.
It is reported in the 50th Edition of the Physicians"" Desk Reference, copyright 1996, p. 753, that food decreases the extent and slightly delays the absorption of metformin delivered by the GLUCOPHAGE(copyright) dosage form. This decrease is shown by approximately a 40% lower peak concentration and a 25% lower AUC in plasma and a 35 minute prolongation of time to peak plasma concentration following administration of a single GLUCOPHAGE(copyright) tablet containing 850 mg of metformin HCl with food compared to the similar tablet administered under fasting conditions.
It is an object of the present invention to provide a controlled or sustained release formulation for an antihyperglycemic drug wherein the bioavailability of the drug is not decreased by the presence of food.
It is a further object of the present invention to provide a controlled or sustained release formulation for an antihyperglycemic drug that does not employ an expanding polymer.
It is also a further object of the present invention to provide a controlled or sustained release formulation for an antihyperglycemic drug that can provide continuous and non-pulsating therapeutic levels of an antihyperglycemic drug to an animal or human in need of such treatment over a twelve hour to twenty-four hour period.
It is an additional object of the present invention to provide a controlled or sustained release formulation for an antihyperglycemic drug that obtains peak plasma levels approximately 8-12 hours after administration.
It is also an object of this invention to provide a controlled or sustained release pharmaceutical tablet having only a homogeneous osmotic core wherein the osmotic core component may be made using ordinary tablet compression techniques.
The foregoing objectives are met by a controlled release dosage form comprising:
(a) a core comprising:
(i) an antihyperglycemic drug;
(ii) optionally a binding agent; and
(iii) optionally an absorption enhancer;
(b) a semipermeable membrane coating surrounding the core; and
(c) at least one passageway in the semipermeable membrane.
The dosage form of the present invention can provide therapeutic levels of the antihyperglycemic drug for twelve to twenty-four hour periods and does not exhibit a decrease in bioavailability if taken with food. In fact, a slight increase in the bioavailability of the antihypoglycemic drug is observed when the controlled release dosage form of the present invention is administered with food. In a preferred embodiment, the dosage form will be administered once a day, ideally with or after a meal and most preferably with or after the evening meal, and provide therapeutic levels of the drug throughout the day with peak plasma levels being obtained between 8-12 hours after administration.

Controlled release oral tablet having a unitary core


A separated coil for a magnetic resonance imaging system has a first partial coil in a first partial casing and a second partial coil in a second partial casing, the first and second partial coils being connected to a connector for connection to the imaging system via a first cable and a second cable, respectively. The coil also has a coupler having a first part disposed in the first partial casing and connected to the first partial coil, and a second part, coupled to the first part, disposed in the second partial casing. The first cable is disposed in the second partial casing, and the second part of the coupler is connected to the connector for connection to the imaging system via the first cable. The signals in the first partial coil are coupled and connected to the cable and the connector via the coupler.

1. Field of the Invention
The present invention relates to a magnetic resonance imaging system and, in particular to a local coil for a magnetic resonance imaging system of the type composed of two separate coil parts.
2. Description of the Prior Art
In a magnetic resonance imaging (MRI) system, due to the application needs, some coils often comprise two parts separated from each other, such as a head-coil and a knee-coil, since there are usually two application needs in clinical practice, namely, the upper and lower parts of a head-coil are used together or the lower part thereof is used alone. Such coils usually are composed of two parts separated from each other. Under normal circumstances, the two parts of the coil which are separated from each other are each located in their own coil casings (housings) respectively.
In the present invention, for a simple description, the two parts of a separate type coil (the upper and lower two parts or the left and right two parts or two parts of other shapes) are referred to as the first partial coil and the second partial coil respectively. Accordingly the coil casing for the first partial coil to fit in is referred to as the first partial casing, the coil casing for the second partial coil to fit in is referred to as the second partial casing. FIG. 1a is an illustration of a separate type coil according to the prior art, and as shown in FIG. 1a, the separate type coil has a first partial coil 12 in the first partial casing 11 and a second partial coil 22 in a second partial casing 21. The second partial coil 22 is connected to a connector 24 for connecting to the imaging system via a second cable 23 which is disposed in the second partial casing 21. In FIG. 1a, assuming that the first partial coil 12 and the second partial coil 22 of the separate type coil comprise three coil units respectively, each coil unit corresponds to a cable. When the first partial coil 12 and the second partial coil 22 of the separate type coil are used together, in order to enable the correct output of the signals from the first partial coil 12, in FIG. 1a, the first cable 13 of the first partial coil 12 is disposed in the first partial casing 11, and the first cable 13 is connected to the connector 14 for connecting to the imaging system. Three coil units of the first partial coil 12 each lead to a cable 13 respectively from the first partial casing 11, the leading cables 13 are connected to the connector 14, and the signals of the first partial coil 12 are outputted to the imaging system for constructing images via the cables 13 and the connector 14. In this method, since the cable 13 and the connector 14 of the first partial coil 12 need to take up additional space, it is not convenient in use.
FIG. 1b is an illustration of another separate type coil according to the prior art, in FIG. 1b, the cables 13 and the connector 14 of the first partial coil 12 are disposed in the second partial casing 21, and the signals of the first partial coil 12 are connected to the cables 13 and the connector 14 in the second partial casing 21 by a metal sheet. As shown in FIG. 1b; the metal sheet is also divided into the upper and lower two parts, a first part 15 and a second part 25 of the metal sheet, wherein, the first part 15 of the metal sheet is located in the first partial casing 11, and connected to the first partial coil 12, the second part 25 of the metal sheet is located in the second partial casing 21, and connected to the connector 14 via the cable 13 in the second partial casing 21. The connector 24 connected to the metal sheet 25 and the connector 24 connected to the second partial coil 22 can be arranged side by side together, like the connector 4 shown in FIG. 1b. However, in this method, as the coil is used over time, the surface of the metal sheet will be rusted or contaminated, thereby causing imperfect electric contacts, in addition, when the second partial coil 22 is used alone, the second part 25 of the uncovered metal sheet will also cause some potential safety problems to a patient.

Magnetic resonance imaging local coil composed of separate parts


An elongated intercore for mounting hollow cores of various lengths for rotation. The intercore includes a plurality of stop members spaced along at least part of the length of the intercore, and which are urged resiliently radially outward between retracted and extended positions. As a result, a core can be slid over the stop members while they are in their retracted position and a first end of a core can abut against a forward facing side of any of the stop members when in an extended position, to prevent the first end from rearward movement. In another aspect, an elongated intercore is provided with a plurality of ring guides spaced apart from one another along a forward end of the intercore and each extending about the intercore. This aspect additionally includes a resilient wire ring which can be positioned within any of the ring guides and restrain forward movement of the core.

In photofinishing, customer images are printed onto a photographic paper. Conventionally this printing has been optical, using a light source which has passed through a negative to be printed to expose the paper. More recently, it has been suggested that the exposure can be from a digitally captured image, using a CRT, laser or light emitting diode printer. At wholesale photofinishing laboratories, where large numbers of images must be printed in a short time, the paper is normally supplied from a web in the form of a roll mounted within a paper dispensing cassette in a known manner. The paper cassette is light tight when closed for transport to and from the printer, and is typically loaded in a dark room to avoid undesirable fogging of the photographic paper. Photographic paper rolls are typically mounted on cardboard cores which in turn are mounted on an intercore dimensioned to fit on a spindle which is driven by the printer. Rotation of the spindle can control dispensing and uptake of a paper roll. Following exposure, the web is chemically developed in a known manner and then cut to yield paper prints of many individual images which are then supplied to respective customers.
Many different printed image formats are typically provided by a single laboratory. To facilitate printing, similar orders may be batched together. However, depending on the print formats required by particular batches, it may be best to use photographic paper rolls of different widths. Thus, when a photographic paper dispensing cassette is reloaded, it may be reloaded with a paper roll of various widths. To correctly position and hold any of various width rolls within the cassette then, the conventional approach has been to provide many different intercores with flanges spaced apart a distance corresponding to the width of the roll which each is intended to mount. One or more flanges are removable to permit mounting of the roll. Such an approach requires a number of spare intercores for a given cassette, each capable of properly mounting only one roll of a particular width. Alternatively, a series of spacers have been used with a single intercore.
It would be desirable then, to provide a way of mounting photographic paper rolls of various widths in a cassette without requiring multiple sizes of intercores or spacers. Furthermore, since cassettes are typically loaded in a darkroom, any means provided to accomplish this, should be simple to operate by an individual even in a darkroom where visibility is extremely low or nonexistent. It would further be desirable in any such mounting apparatus that there not be a series of loose parts which may be difficult to find and manipulate in a darkroom.


An enhanced method of testing semiconductor devices having nonvolatile elements by determining regions of the semiconductor having differing orders of probability that a defect will occur. The enhanced method of testing includes testing of regions from the highest probability to the lowest probability of having a defect. Nonvolatile memory elements in the region being tested are placed in a high impedance state, bypass circuits in the region being tested are activated to bypass the nonvolatile memory elements that control the state of elements in the region being tested and test vectors are applied to the elements that are controlled by the bypassed nonvolatile memory elements. This procedure is repeated for the next untested region having the highest probability of having a defect until all regions have been tested.

1. Field of the Invention
This invention relates generally to an enhanced method of testing semiconductor devices. More specifically, this invention relates to an enhanced method of testing regions of semiconductor devices in order of probability that a defect will occur in the regions. Even more specifically, this invention relates to an enhanced method of testing semiconductor devices that contain nonvolatile memory elements. Furthermore, this invention relates to an enhanced method of testing semiconductor devices that contain nonvolatile memory elements that avoids the necessity for the multiple programming and erasing of the nonvolatile memory elements.
2. Discussion of the Related Art
There are many semiconductor devices that utilize nonvolatile devices such as EPROMs (Erasable Programmable Read Only Memories) and EEPROMs (Electrically Erasable Read Only Memories) that retain their contents upon termination of power. One such device is a programmable logic device (PLD), which is a programmable integrated circuit that allows the end user or customer of the circuit to customize the logic functions the circuit is to perform. The term PLD is a generic term and includes other "array" programmable logic devices, such as PLAs (Programmable Logic Arrays), PALs (Programmable Array Logic) devices, and GALs (Generic Array Logic) devices. These programmable logic devices can be programmed to perform logic functions previously performed by small, medium and large-scale integrated circuits.
When a typical programmable logic device is delivered to a customer, it is not yet capable of performing any specific function. The customer, using software typically supplied by the manufacturer of the programmable logic devices, programs the PLD to perform the specific function or functions required by the customer's application. The PLD is then capable of functioning in a larger system designed by the customer in the same way dedicated logic chips would perform if used in the system.
The manufacture and sale of PLDs has become a substantial and important sector of the semiconductor industry. The success of these devices has caused a dramatic increase in the demand for programmable devices that can be programmed to accommodate larger and more complex customer programmable patterns. Because customers expect and demand devices that are 100% tested, the importance of efficient test methodologies has become paramount. It is well known in the semiconductor industry that as semiconductor products mature, their selling prices fall dramatically. This fall in selling prices makes it even more imperative that manufacturing costs and related testing costs be reduced in order to maintain a reasonable margin of profitability for the devices as they mature.
A typical PLD includes a number of product term arrays (PTAs), which are arrays of logic cells that can be individually programmed and arbitrarily interconnected to each other by the customer. The interconnections provide further internal input signals as well as output signals that permit the performance of highly complex combinational and sequential logic functions. The customer is provided with a "customer" program that is implemented in the PLD by allowing the customer to set the states of programmable elements in the PTAs. The programmable elements in the PTAs are memory cells that may be volatile memory cells such as SRAMs that lose their programmed state upon termination of power to the system. The use of volatile memory cells requires the volatile memory cells to be reprogrammed each time power is applied to the circuit. Alternatively, the memory cells may be nonvolatile memory cells, such as EPROMs and EEPROMs, which retain their content upon termination of power thus obviating the requirement to reprogram the memory cells each time power is terminated and reapplied to the circuit.
Programmable logic devices also include multipurpose logic blocks typically called macrocells. These multipurpose logic blocks perform various functions of synchronous and/or asynchronous functions as configured by the customer using the software provided by the manufacturer to program memory cells that control the configuration of the macrocells.
In order to provide the customer with the maximum flexibility in the programming of the PLD, an interconnection harness is provided that can be programmed to provide a path from any input pad on the PAD to any PTA and virtually to any other point within the PLD.
As discussed above, as PLDs have migrated towards higher logical capacity, the testing of the PTAs, the macrocells and the interconnection harness has surfaced to be a non-trivial problem. This problem affects both the costs of the development of high quality test vectors and the cost of testing each PLD. A major portion of testing cost is a direct function of test time.
Presently, in order to fully test the interconnection and logic capacity of a PLD that contains nonvolatile memory elements, many program/erase cycles are required, which substantially increases the testing time for each added cycle. As the programmable logic devices continue to increase in size and complexity it is becoming more difficult and time consuming to guarantee that all of the interconnection circuitry implemented in the PLD has the capability of functioning correctly as programmed by the customer. For example, one implementation of Interconnection circuitry is to use N to 1 multiplexers. Since it is necessary to localize any defects that are detected, both as a quality issue for the test vectors and to assess the quality of fabricated silicon, each input to each multiplexer must be tested separately. Since each input to each of these multiplexers is controlled by a separately programmed nonvolatile memory element a theoretical minimum number of program/erase cycle can be determined by finding the multiplexer with the largest number of inputs. This means that N becomes the minimum number of program/erase cycles. It should be appreciated that more than this theoretical minimum number of program/erase cycles may be required because many other factors, such as additional architectural complexities may add required program/erase cycles.
In order to test the increasingly complex PLDs economically, it is mandatory that the high number of program/erase cycles be controlled or reduced. Of paramount importance is the implementation of a testing methodology that has the capability to identify defective die, as soon as possible, and then to cease testing the identified defective die since test costs are significant. The test costs become even more significant as the selling price of the device decreases in the marketplace. The continued expenditure of testing resources on defective die increases the test cost of good die, since the continued cost of testing defective dice is amortized over the remaining good devices. Currently the testing methodology for PLDs is a "brute force" methodology in which test vectors are generated for each and every interconnect combination in the device without considering in which area of the device it is more likely for manufacturing defects to occur.
Therefore, what is needed is a testing methodology for testing programmable logic devices that can quickly and economically identify defective die as soon as possible in the testing cycle and then to cease testing the defective die. In addition, what is needed is a testing methodology for testing programmable logic devices that avoids the necessity for the program/erase cycle for each test.

Enhanced method of testing semiconductor devices having nonvolatile elements


The investment liquidation and purchase adjustment method is an investment model for open-ended investments that takes into account the net asset value (NAV) of the mutual fund and an accumulated stock brokerage transaction commission fees. The accumulated commission fees are added to the net asset value per share prior to the purchase of shares of the mutual fund. Alternatively, the accumulated commission fees are subtracted from the net asset value per share prior to the liquidation of the shares. These additional fees flow into the assets of the mutual fund. As accumulated brokerage transaction commissions change each day because of the trading of the positions in the mutual fund, the brokerage transaction commission's percentage change on a daily basis, too. This also solves the problem of maintaining the true asset value for existing shareholders when there are share liquidations by existing shareholders, protecting the true asset value for the remaining existing shareholders.

1. Field of the Invention
The present invention relates generally to financial investment management, and more specifically, to a computerized investment liquidation and purchase adjustment method for open-ended investments.
2. Description of the Related Art
The largest segment of open-ended investments is the field of mutual funds. A mutual fund is a professionally managed type of collective investment scheme that pools money from many investors and invests it in stocks, bonds, short-term money market instruments, and/or other securities. The mutual fund will have a fund manager that trades the pooled money on a regular basis. Currently, the worldwide value of all mutual funds totals more than $26 trillion.
Since 1940, there have been three basic types of investment companies in the United States: open-end funds, also known in the US as mutual funds; unit investment trusts (UITs); ETFs; and closed-end funds. Similar funds also operate in Canada. However, in the rest of the world, mutual fund is used as a generic term for various types of collective investment vehicles, such as unit trusts, open-ended investment companies (OEICs), unitized insurance funds, and undertakings for collective investments in transferable securities (UCITS).
Massachusetts Investors Trust (now MFS Investment Management) was founded on Mar. 21, 1924, and, after one year, it had 200 shareholders and $392,000 in assets. The entire industry, which included a few closed-end funds represented less than $10 million in 1924.
The stock market crash of 1929 hindered the growth of mutual funds. In response to the stock market crash, Congress passed the Securities Act of 1933 and the Securities Exchange Act of 1934. These laws require that a fund be registered with the Securities and Exchange Commission (SEC) and provide prospective investors with a prospectus that contains required disclosures about the fund, the securities themselves, and fund manager. The SEC helped draft the Investment Company Act of 1940, which sets forth the guidelines with which all SEC-registered funds today must comply.
Since the Investment Company Act of 1940, a mutual fund is one of three basic types of investment companies available in the United States. Mutual funds can invest in many kinds of securities. The most common are cash instruments, stock, and bonds, but there are hundreds of sub-categories. Stock funds, for instance, can invest primarily in the shares of a particular industry, such as technology or utilities. These are known as sector funds. Bond funds can vary according to risk (e.g., high-yield junk bonds or investment-grade corporate bonds), type of issuers (e.g., government agencies, corporations, or municipalities), or maturity of the bonds (short- or long-term). Both stock and bond funds can invest in primarily U.S. securities (domestic funds), both U.S. and foreign securities (global funds), or primarily foreign securities (international funds).
Most mutual funds' investment portfolios are continually adjusted under the supervision of a professional manager, who forecasts cash flows into and out of the fund by investors, as well as the future performance of investments appropriate for the fund and chooses those which he or she believes will most closely match the fund's stated investment objective. A mutual fund is administered under an advisory contract with a management company, which may hire or fire fund managers.
Mutual funds are subject to a special set of regulatory, accounting, and tax rules. In the U.S., unlike most other types of business entities, they are not taxed on their income as long as they distribute 90% of it to their shareholders and the funds meet certain diversification requirements in the Internal Revenue Code. Also, the type of income they earn is often unchanged as it passes through to the shareholders. Mutual fund distributions of tax-free municipal bond income are tax-free to the shareholder. Taxable distributions can be either ordinary income or capital gains, depending on how the fund earned those distributions. Net losses are not distributed or passed through to fund investors.
Running a mutual fund involves costs, including shareholder transaction costs, investment advisory fees, and marketing and distribution expenses. Funds pass along these costs to investors in a number of ways. Mutual fund fees and expenses are charges that may be incurred by investors who hold mutual funds.
Generally, unlike past performance of the fund, expenses are very predictive. Funds with high expenses ratios tend to continue to have high expenses ratios. An investor can examine a fund's "Financial Highlights" which is contained in both the periodic financial reports and the fund's prospectus, and determine a fund's expense ratio over the last five years (if the fund has five years of history). It is very hard for a fund to significantly lower its expense ratio once it has had a few years of operational history. This is because funds have both fixed and variable expenses, but most expenses are variable. Variable costs are fixed on a percentage basis. For example, assuming there are no breakpoints, a 0.75% management fee will always consume 0.75% of fund assets, regardless of any increase in assets under management. The total management fee will vary based on the assets under management, but it will always be 0.75% of assets. Fixed costs (such as rent or an audit fee) vary on a percentage basis because the lump sum rent/audit amount as a percentage will vary depending on the amount of assets a fund has acquired. Thus, most of a fund's expenses behave as a variable expense and thus, are a constant fixed percentage of fund assets. It is therefore, very hard for a fund to significantly reduce its expense ratio after it has some history. Thus, if an investor buys a fund with a high expense ratio that has some history, he/she should not expect any significant reduction.
There are 3 broad investment categories for mutual funds (equity, bond, and money market—in declining order of historical returns). That is an over simplification but adequate to explain the effect of expenses. In an equity fund where the historical gross return might be 10%, a 1% expense ratio will consume approximately 10% of the investor's return. In a bond fund where the historical gross return might be 8%, a 1% expense ratio will consume approximately 12.5% of the investor's return. In a money market fund where the historical gross return might be 5%, a 1% expense ratio will consume approximately 20% of the investor's historical total return. Thus, an investor must consider a fund's expense ratio as it relates to the type of investments a fund will hold.
Mutual funds bear expenses similar to other companies. The fee structure of a mutual fund can be divided into two or three main components: management fee, nonmanagement expense, and 12b-1/non-12b-1 fees. All expenses are expressed as a percentage of the average daily net assets of the fund.
A management fee for the fund is usually synonymous with the contractual investment advisory fee charged for the management of a fund's investments. However, as many fund companies include administrative fees in the advisory fee component, when attempting to compare the total management expenses of different funds, it is helpful to define management fee as equal to the contractual advisory fee+the contractual administrator fee. This "levels the playing field" when comparing management fee components across multiple funds.
Contractual advisory fees may be structured as "flat-rate" fees, i.e., a single fee charged to the fund, regardless of the asset size of the fund. However, many funds have contractual fees which include breakpoints, so that as the value of a fund's assets increases, the advisory fee paid decreases. Another way in which the advisory fees remain competitive is by structuring the fee so that it is based on the value of all of the assets of a group or a complex of funds rather than those of a single fund.
Apart from the management fee, there are certain non-management expenses which most funds must pay. Some of the more significant (in terms of amount) non-management expenses are: transfer agent expenses (this is usually the person you get on the other end of the phone line when you want to purchase/sell shares of a fund), custodian expense (the fund's assets are kept in custody by a bank which charges a custody fee), legal/audit expense, fund accounting expense, registration expense (the SEC charges a registration fee when funds file registration statements with it), board of directors/trustees expense (the disinterested members of the board who oversee the fund are usually paid a fee for their time spent at meetings), and printing and postage expense (incurred when printing and delivering shareholder reports).
Fees and expenses borne by the investor vary based on the arrangement made with the investor's broker. Sales loads (or contingent deferred sales loads (CDSL)) are not included in the fund's total expense ratio (TER) because they do not pass through the statement of operations for the fund. Additionally, funds may charge early redemption fees to discourage investors from swapping money into and out of the fund quickly, which may force the fund to make bad trades to obtain the necessary liquidity. For example, Fidelity Diversified International Fund (FDIVX) charges a 1 percent fee on money removed from the fund in less than 30 days.
An additional expense which does not pass through the statement of operations and cannot be controlled by the investor is brokerage transaction commissions. Brokerage transaction commissions are incorporated into the price of the fund and are reported usually 3 months after the fund's annual report in the statement of additional information. Brokerage transaction commissions are directly related to portfolio turnover (portfolio turnover refers to the number of times the fund's assets are bought and sold over the course of a year). Usually the higher the rate of the portfolio turnover, the higher the brokerage transaction commissions. The advisors of mutual fund companies are required to achieve "best execution" through brokerage arrangements so that the commissions charged to the fund will not be excessive.
According to data from Greenwich Associates presented in testimony to the House Committee on Financial Services (Harold Bradley of American Century Management, Mar. 12, 2003), mutual funds pay an average of between 5.1 and 5.5 cents per share in commissions to make securities transactions—a rate that has not changed significantly in the past decade.
Existing shareholders in open-ended investment vehicles such as mutual funds, ETFs, hedge funds, etc., are continuously and dually monetarily disadvantaged when new shares or units are purchased by new investors. Additionally, the same situation occurs when exiting shareholders redeem their shares in the investment vehicle.
New shares in existing mutual funds are bought without consideration to the brokerage transaction commissions (or trading costs) that were paid in acquiring the fund's existing portfolio, thus giving the new investors a slight price advantage, and at the same time creating a slight price disadvantage to existing shareholders.
Thus, a computerized method for open-ended investments solving the aforementioned problems is desired.

Computerized method for open-ended investments


Applications which function under a first operating system also function when it becomes necessary to call into action a second operating system due to provision having been made for configuration and other settings necessary to the execution of such applications (here generically called policy settings or policy source data) to be made available to the second operating system.

It is known to operate computer systems with multiple operating systems. In particular, it is common place to provide systems with a so-called "dual boot" capability. Oftentimes, in providing dual boot capability, the multiple operating system function entirely independently one of another.
It is also known to provide for the capability of shifting to a second operating system should there be some failure in the operation of a first operation system. What has been known as the Lenovo rescue and recovery capability is one such implementation. In such an implementation, a system has first and second operating systems stored accessibly to the system and can move from the first to the second either automatically on certain identified failures of the first operating system or at the selection of a user of the system in other circumstances. In commercially available implementations of such operating systems, Microsoft products have been used, such as a Windows XP or other primary operating system as the first and a Windows PE or embedded system as the second.
Regardless of whether Microsoft products or other operating systems are used as the first and second operating systems, a problem is presented in assuring that applications which function under the first operating system also function under the second operating system. This can be important in restoring the functionality of a system, where application programs other than the operating system must be used to correct faults in system configuration or operations which may have caused the failure of the first operating system.

Apparatus, method and program product for policy synchronization


An iontophoretic patch for transdermal delivery of biologically active agents includes at least two electrodes in contact with at least two hydrogel reservoirs. At least one of the hydrogel reservoirs carries at least one active agent and, in use of the iontophoretic patch, is disposed on a user's skin and delivers at least one active agent into the skin. The patch includes a control unit to generate a stimulation pattern having stimulation parameters delivered to stimuli locations on the skin. A stimulation unit generates a time sequence of pulses from the stimulation parameters generated by the control unit. The patch further includes a demultiplexing unit configured to perform independent spatio-temporal distribution of the electrical pulses in the time sequence of pulses to at least one electrode; at least one optical sensing system, for continuously measuring an amount of the active agent in the hydrogel reservoir; and a feedback unit.

From wound healing to immuno-modulation and drug delivery, a large number of therapeutic strategies rely on the application of electric fields and currents to and through the skin with an electronic device comprising skin-contacting electrodes.
The main application of such devices is currently transdermal drug delivery, which represents an alternative to oral delivery of drugs and is poised to provide an alternative to hypodermic injection too. Currently the transdermal route has become one of the most successful and innovative focus in drug delivery, with around 40% of the drug candidates being under clinical evaluation related to transdermal or dermal systems. Transdermal delivery of drugs through the skin to the systemic circulation provides a convenient route of administration for a variety of clinical indications (Front Line Strategic Consulting Inc., 2002). The benefits of using transdermal drug delivery include improved systemic bioavailability resulting from bypassing the first metabolism. Variables due to oral administration, such as pH, the presence of food or enzymes and transit times can all be eliminated.
In the development of new transdermal drug delivery devices the object is most often to obtain controlled, predictable and reproducible release of drugs into the blood stream of the patient. The transdermal device acts as a drug reservoir and controls the rate of drug transfer. When the transdermal flux is controlled by the device instead of skin, delivery of the drug is more reproducible leading to smaller inter and intra subject variations, since the drug release from the device can be controlled more accurately than the permeability of the skin (Guy et al., 1992).
One of the possible techniques used for transdermal delivery is called iontophoresis. It is the application of an electric potential that maintains a constant electric current across the skin and enhances the delivery of ionized as well as unionized moieties (Williams et al., 1992). The ion movement in the skin and in a hydrogel is governed by the combined influence of the ionic concentration gradient and the electric field, as defined by the Nernst-Planck equation. When a direct electric current activates the planar electrodes of an electrode array placed over a piece of skin, anions—ions with a negative charge—are repelled from the negative electrode. Cations—positively charged ions—are similarly repelled from the positive electrode. Because of the shape of the electric field generated by the planar electrodes, ionic movement forms an electric current driven through the skin in the direction of the electric potential gradient. The net effect of iontophoresis becomes evident whenever the movement of the ions due to the electric field is dominant over passive diffusion of ions through the skin. The higher the current density and the amount of time the electric current flows through the skin, the larger the quantity of ions that penetrate into the skin. Iontophoresis is capable of expanding the range of compounds that can be delivered transdermally. Along with the benefits of bypassing hepatic first pass effect, and higher patient compliance, the additional advantages that the iontophoretic technique offers can be summarized as follows (Williams et al., 1992, Williams et al., 1991 and Glikfeld et al., 1988): delivery of both ionized and unionized drugs; depending on the current applied it is enabling continuous or pulsatile delivery of drug; permitting easier termination of drug delivery; offering better control over the amount of drug delivered since the amount of compound delivered depends on applied current, duration of applied current, and area of skin exposed to the current; restoration/preservation of the skin barrier functions without producing severe skin irritation; improving the delivery of polar molecules as well as high molecular weight compounds; ability to be used for systemic delivery or local (topical) delivery of drugs; reducing considerably inter and/or intra subject variability in view of the fact that the rate of drug delivery is more dependent on applied current than on stratum corneum characteristics.
The control of the dosage of drug delivered into the body is a critical issue for many medical applications. Some solutions, such as the ones provided by US2001009983 (A1) and U.S. Pat. No. 9,327,105 (B2), have been proposed to release a predefined current profile achieving this way a limited control on the drug delivered.
In order to overcome such limitation, other disclosures as an example U.S. Pat. No. 8,428,709 (B1), EP2949359 (A1), EP2810688 (B1), WO2008131072 (A1), US2007021711 (A1) and U.S. Pat. No. 6,546,282 (B1), provide a control system for the iontophoretic device based on the measurement of the current delivered by the device. The measured current value is used by the controller to adjust the current to a predefined delivering profile that matches the estimated drug delivered into the body. In an alternative proposal, EP0616545 (B1) measures the charge transferred to display the estimated cumulative amount of drug delivered into the body.
Another alternative approach to control how much drug is delivered into the body is provided, for example, in US2016279434 (A1), EP0830175 (B1) and US2009118710 (A1) where a controller modifies the release of drug depending on external parameters such as user age, skin type or environmental parameters such as local temperature and atmospheric pressure), or depending on the measurement of body parameters such as glucose concentration, or depending on the drug reservoir attached to the device.
Another alternative approach to control how drug is released into the body is provided by different designs of iontophoretic devices. As an example, US2004193089 (A1), uses a network of electrodes to achieve a spatial release of the drug. As another example EP1067985 (B1), measures impedance to control the electric field and hence how drug is delivered into the body.
Clearly, despite a great number of proposals in the field of iontophoresis-based devices, the control of the dosage, spatial and temporal delivery profile is based on measurements of current or voltage and consequent estimation of amounts of drug that is delivered. This approach has one major drawback, that is related to the fact that in all iontophoretic devices the current measured is reflecting the movement of all ions in the system and predominantly this current has origin in small mobile ions of the electrolyte solution and only a minor part of the current can be attributed to the movement and charge transfer of the drug molecules themselves. Having in mind the correlation between net current and the current that originally comes from charged drug molecules, a proportional relation may be established, but still dependent on many variable factors coupled with inter subject differences.
Hence, one of the current challenges is monitoring in real time the amount of drug that is delivered to the skin. Measuring this amount of drug on or in the skin directly involves a very complex methodology that is very difficult to integrate in a wearable or single use device.

Device and method for controlled and monitored transdermal delivery of active agents and use thereof

FUNDACIÓN TECNALIA RESEARCH & INNOVATION


It is possible to provide a frequency component measuring device capable of narrowing the range of transmission frequency of a local oscillator, preventing degradation of the level measurement accuracy, and measuring the level of a modulation wave. The device includes: a local oscillator (24) capable of performing sweep in a predetermined frequency range; a mixer (22) for mixing a local oscillation signal outputted from the local oscillator (24) and a measured signal so as to subject the measured signal to a frequency conversion; a plurality of intermediate-frequency filters (44, 46) for extracting and outputting components of different intermediate frequencies from a signal outputted from the mixer (22); and an image removal processing section (66) for performing image removal according to the plurality of intermediate-frequency signals separately outputted from the intermediate-frequency filters (44, 46) corresponding to frequency sweep operations performed by the local oscillator (24) more than once.

A spectrum analyzer has been conventionally known that is adapted to remove an image frequency of an input signal by performing frequency sweep twice (for example, see Japanese Patent Laid-Open No. 08-233875, pp. 3-4, FIGS. 1-2). In this spectrum analyzer, two types of spectrum data are obtained by performing frequency sweep twice by changing the frequency range of an oscillation signal of a local oscillator to be inputted to an external mixer (an Nth order harmonic wave included in an output signal of the local oscillator is used as the oscillation signal), and image removal processing is performed by selecting a smaller data value corresponding to the same frequency.


A histogram is generated on the basis of the pixel value of an image. An LUT used for changing the dynamic range of the image is generated on the basis of the histogram value in each pixel value interval of the generated histogram. The dynamic range of the image is changed on the basis of the generated LUT.

As the digital technology progresses recently, people convert a radiographic image into a digital image signal (the value of a pixel contained in the digital image signal will be referred to as a pixel value), execute image processing for the digital image signal, and display the image on a display device such as a CRT or output the image to a film.
When a radiographic image is sensed, generally, tone conversion processing is executed by using a linear LUT or an LUT with an S-shaped tone conversion curve representing the characteristic of a film to make the converted digital image signal suitable for display or film output.
In X-ray images of human bodies, the dynamic range of the subject changes depending on the individual difference between subjects or radiography conditions. Hence, to optimize the minimum and maximum values of the dynamic range of the subject in advance, the dynamic range of the subject is changed (compressed or expanded) (e.g., reference 1).
According to this method, processing is performed to make the dynamic range of the subject fall within the given dynamic range of the output medium. For this reason, the performance of the output medium can be maximized, and an output image easy to diagnose can be obtained.
In some cases, dynamic range compression processing is executed to make the dynamic range fit in that of the output medium while maintaining the contrast of a fine structure. An example of this method is described in, e.g., reference 2.
In this method, let SD be the pixel value of an image which has undergone processing, Sorg be the pixel value of the original image, and Sus be the average pixel value (pixel value of the smoothed image) obtained by calculating the moving average of the original image on the basis of a mask size of M×M pixels. The processing is executed bySD=Sorg+f(Sus)  (1)Sus=ΣSorg/M2  (2)using a monotone decreasing function f(x). Equation (1) can be rewritten to
                                                                        S                D                            =                                                                            (                                                            S                      org                                        -                    Sus                                    )                                +                                  (                                                            f                                                                    (                        Sus                        )                                                              +                    Sus                                    )                                                                                =                                                                            (                                                            S                      org                                        -                    Sus                                    )                                +                                  f                                                                                1                                                        (                    Sus                    )                                                                                (        3        )
Since Sorg−Sus corresponds to the high-frequency component of the image, this processing can also be regarded as dynamic range change processing limited to a low-frequency component. Hence, the fine structure corresponding to the high-frequency component can be maintained.
[Reference 1] "Computer Imaging Processing Approach" edited by Hideyuki Tamura, (Japan), Soken-Shuppan, pp. 95-97
[Reference 2] Anan et al, "Journal of Japan Radiological Society", August 1989, Vol. 45, No. 8, p. 1030
In the method described in reference 1, however, when the dynamic range of the image is compressed excessively, the contrast may be too low.
Conversely, when the dynamic range is expanded excessively, the contrast may be too high. The compression or expansion processing is executed uniformly for the entire image. When viewed from the local region basis, an unnecessarily wide dynamic range may be assigned to a small information amount, or a narrow dynamic range may be assigned even when the information amount is large.
In the method described in reference 2, the dynamic range is changed for only a low-frequency component. Hence, even when the dynamic range is compressed excessively, no shortage of contrast occurs.
However, since the low- and high-frequency components are unbalanced, artifacts are generated by overshoot or undershoot. This is particularly conspicuous near an edge where the gradient of pixel value is large. That is, artifacts are generated when a low frequency is assigned to a narrow dynamic range in spite of a large information amount as an edge.

Image processing apparatus and method for changing the dynamic range of an image