A slide surface construction is formed of an aggregate of metal crystals on a surface of a slide member. The area rate A of pyramid-shaped metal crystals in the slide surface is in the range of A.gtoreq.40%, and the oxygen (O) content and/or the phosphorous (P) content in the aggregate is in a range of 0.gtoreq.0.2% by weight and P.gtoreq.0.04% by weight. The slide surface takes on an intricate aspect due to the presence of the large number of hexagonal pyramid-shaped metal crystals and hence, has a good oil retention. In addition, the wearing of the hexagonal pyramid-shaped metal crystals is inhibited by an increase in hardness caused by the oxygen contained, and therefore, the oil retention is maintained. Thus, the slide surface construction exhibits an excellent seizure resistance. In addition to oxygen (O) and/or phosphorous (P), the elements that may be added to the aggregate include hydrogen (H), carbon (C) and boron (B).

1. Field of the Invention
The present invention relates to a slide surface construction, and particularly, to a slide surface construction formed of an aggregate of metal crystals and having a high hardness.
2. Description of the Related Art
Such conventionally known slide surface constructions include an Fe-plated layer, for example, which is provided on outer peripheral surfaces of a land portion and a skirt portion of a substrate made of a steel in a piston for an internal combustion engine for the purpose of providing an enhancement in wear resistance.
However, the known slide surface construction has a problem that under existing circumstances where speed and output of the internal combustion engine have tended to increase, the known slide surface construction is not sufficient in oil retaining property, namely, oil retention and is poor in seizure resistance due to a relatively smooth slide surface thereof.
Therefore, the present applicant has proposed a slide surface construction including a large number of pyramid-shaped metal crystals in a slide surface thereof (for example, see Japanese Patent Application Laid-open No.174089/94).
If the slide surface construction is formed in this manner, adjacent pyramid-shaped metal crystals assume mutually biting states and hence, the slide surface takes on an intricate aspect comprising a large number of fine crests, a large number of fine valleys formed between the crests, and a large number of fine swamps formed due to the mutual biting of the crests. Therefore, the slide surface construction has a good oil retention. Thus, the seizure resistance of the slide surface construction is enhanced.
However, as a result of various reviews of the slide surface construction, it has been made clear that the slide surface construction has a relatively low hardness and hence, in order to accommodate a more severe sliding environment, it is necessary to enhance the hardness of the slide surface construction to inhibit or resist the wearing of the pyramid-shaped metal crystals in such sliding environment, thereby allowing the slide surface construction to maintain a good oil retention.


In accordance with an embodiment, a wireless communication device constituting a wireless mesh network that transmits information through multi-hop communication comprises a communication section configured to transmit a message addressed to a wireless communication device different from its own wireless communication device through broadcast communication on a first frequency channel; and a control section configured to change a communication channel of the communication section from the first frequency channel to a second frequency channel for communication of a response signal responding to the message after the message is transmitted by the communication section.

In a retail store such as a supermarket, a POS (Point Of Sales) terminal is used. Since the POS terminal executes various processing relating to a transaction, a high reliability is required, and maintenance and management become important for the POS terminal. As a maintenance and management method, for example, a method for constructing a mesh network among a plurality of POS terminals to transmit information relating to maintenance is considered.
A method of performing broadcast communication by adding its own address to a header of a message in the mesh network is known. In such a method, a node that receives the message similarly adds its own address, repeats the broadcast communication, and then transmits the message to a target node. The target node refers to the addresses stored in the header to transfer a reply to the node which is a transmission source in reverse.


To improve the use efficiency of materials and provide a technique of fabricating a display device by a simple process. The method includes the steps of providing a mask on a conductive layer, forming an insulating film over the conductive layer provided with the mask, removing the mask to form an insulating layer having an opening; and forming a conductive film in the opening so as to be in contact with the exposed conductive layer, whereby the conductive layer and the conductive film can be electrically connected through the insulating layer. The shape of the opening reflects the shape of the mask. A mask having a columnar shape (e.g., a prism, a cylinder, or a triangular prism), a needle shape, or the like can be used.

1. Field of the Invention
The present invention relates to a method of fabricating a display device having a stacked structure of thin films. More specifically, the invention relates to the step of forming an opening in a thin film in the process of fabricating a display device.
2. Description of the Related Art
Thin film transistors (also referred to as "TFTs") and electronic circuits having TFTs are fabricated by the steps of stacking various thin films such as a semiconductor film, an insulating film, and a conductive film, and forming predetermined patterns in the films by a photolithography technique as appropriate. A photolithography technique is a technique of transferring a circuit pattern or the like, which is called a photomask and is formed from a non-light-transmissive material on a transparent flat plate, onto a substrate through light exposure, and is widely used in the process of fabricating semiconductor integrated circuits and the like.
A fabrication process of a semiconductor device using a conventional photolithography technique involves a number of steps such as light exposure, development, baking, and peeling for the process of handling a mask pattern which is formed from a photosensitive organic resin material called photoresist. Therefore, the more the number of photolithography steps is increased, the more the fabrication cost is inevitably increased. In order to overcome such drawbacks, a fabrication process of TFTs with a reduced number of photolithography steps has been studied (e.g., see Reference 1: Japanese Published Patent Application No. 2000-133636). In Reference 1, a resist mask formed by photolithography steps which is used once is subjected to cubical expansion by swelling treatment so that the mask can be used again.

Method of forming display device that includes removing mask to form opening in insulating film

Semiconductor Energy Laboratory Co., Ltd.


The present inventions relate to a method and apparatus for adding Automatic Meter Reading (AMR) capabilities to utility meters that generate a magnetic field comprising magnetic flux that varies proportionally with the rate of resource consumption. The apparatus comprises a dual magnetic field sensor unit for detecting variations in the magnetic flux density for the magnetic field. The sensor unit may be compact in size so that it can be positioned within a utility meter. The sensor unit may be operatively connected to a data-unit located outside the utility meter. The data unit may be further configured for storing processed or unprocessed sensor signals and is connected to a transmitter.

Utility meters, including mechanical, electromechanical, and solid state meters, are well known and have been used for many years to measure the consumption of resources such as water, gas and electricity. Water meters, for example, generate data indicative of the consumption of water, where such data is used for billing purposes. Initially, utility meters were mechanical devices. As electronic technology advanced, such technology became smaller and less expensive, and thus, more suitable for use in the highly competitive and cost sensitive utility meter market. As such, the use of electromechanical (hybrid meters) and electronic meters has become more common. Indeed, most modem electricity meters are electronic meters (static meters).
While there are various techniques for measuring fluid flow, most fluid meters are still electromechanical devices. Such fluid meters frequently comprise major components such as a fluid chamber and a register. The fluid chamber often has a fluid input and a fluid output which allows a fluid to flow through the fluid chamber. Typically, a rotating-device is placed within the fluid chamber in the path of fluid flow where such fluid flow causes the rotating device to rotate in proportion to the rate of fluid flowing through the meter.
Various means exists for making the rotations of such a rotating device detectable by components in the register. For example, in many prior art meters, the rotating-device and components in the register are magnetically coupled. In such meters, the rotating-device may be constructed from a magnetic material or have magnetic material associated with the rotating-device. As the rotating device rotates in response to fluid flow through the meter, a rotating magnetic field is created. Components in the register count the number of rotations and use such data to determine and display consumption data. U.S. Pat. No. 6,604,434 issued to Hamilton et al. discloses such a meter and such patent is incorporated by this reference for all purposes.
Traditionally, meter reading personnel would periodically travel to each site where a utility meter was installed, inspect a meter installation and manually record the consumption data. The customer would then receive a bill based on such collected data. Today, modern meters are increasingly equipped with Automatic Meter Reading (AMR) capabilities which provide utility meters with the capability of automatically communicating consumption data to a remote location. Such technology greatly simplifies and lowers the cost of collecting consumption data for billing purposes. However, utility companies have installed millions of utility meters that do not have AMR capabilities. For utility companies to upgrade such meters with AMR capabilities, it has been necessary to replace the entire meter or major meter components (e.g. one or both of the register and fluid chamber). Such upgrades are very expensive. Consequently, there is a need for technology that allows utility companies to upgrade non-AMR equipped utility meters with AMR technology without requiring the replacement of major components of the meter.
Additionally, as noted above, utility meters collect consumption data used by a utility company to bill a utility company's customers. Thus, accuracy in collecting consumption data is critical. Similarly, utility meters are expected to operate accurately for years without failure. Finally, utility companies expect such functionality at the lowest possible price. Consequently, there is a need for a system for adding AMR capabilities to old and new utility meters that is accurate, dependable and cost effective.
Yet another issue that designers of utility meter technology face is supplying power to the meter electronics. In many utility meter environments, easily accessible power from an electrical utility grid is not available. As a result, such meter technology is often powered by a depletable power source such as batteries. Therefore there is a need for AMR technology designed for minimal power consumption so that such technology may be powered for extended periods of time by depletable power sources. In addition, for some installations, there is a need for an apparatus and method for recharging the depletable power source.
To minimize power consumption and component stress, prior art meters employ AMR technology that places the AMR system in an off state. When data is needed from such prior art AMR equipped systems, a remote AMR reader sends a wakeup signal to the AMR equipped meter to activate the transmitter. The transmitter then transmits data to the remote AMR reader. While such a system works well, it requires the remote AMR reader to have relatively expensive transmitter capabilities and the AMR systems installed at the meter to have relatively expensive receiver capabilities. Thus, while power consumption may be minimized for such a system, the technology needed to transmit and receive a wakeup signal adds cost of the system. Consequently, there is a need for an AMR system that can place the AMR transmitter in a sleep mode without requiring a wakeup signal.
Another problem with some prior art AMR systems that transmit a signal to a remote location is that the low cost design of one component might add cost to a second component. For example, some prior art AMR transmitters may be designed for low cost by using lower quality, relatively less expensive components. For such transmitters, the carrier frequency of the transmitter signal may drift over time or the power level of the transmitted signal may weaken over time. While such systems may be designed to minimize the cost of the AMR transmitter technology located at the utility meter, such a design adds costs to the receiver electronics located at a remote location. Thus, there is a need for an AMR transmitter design that minimizes transmitter costs without adding significant costs to the receiver technology design.
Another issue the designers of AMR systems face relates to the diversity of register designs among different meter manufactures and the diverse communication protocols used by such registers. In the area of water meters, for example, while most major water meter manufacturers include a register design incorporating a three conductor interface to facilitate communication with electronic device outside the register (such as a transmitter), such registers use different communication protocols. In most prior art meters, the AMR transmitter communication hardware must be manually configured before the AMR transmitter can communicate with the meter register. Manually configuring an AMR transmitter with the proper communication protocol from a plurality of possible communication protocols is undesirable as it as cost to the AMR transmitter installation process, requires extra training for meter installation personnel, and provides an opportunity for human error. U.S. Pat. No. 5,523,751 issued to Byford et al., incorporated by this reference for all purposes, discloses a meter reading apparatus, such as a hand held probe, which has the ability to automatically communication with a plurality of data sources. While the Byford et al. invention works well for its intended purpose, such a method consumes too much power for a transmitter powered by a depletable power source installed at a customer site. Thus, there is a need for an auto communication configuration apparatus and method that minimizes power consumption and is designed for devices powered by depletable power sources and installed at remote customer locations.

Abstract: To minimize power consumption, the magnetic field sensors may be configured to have sensor on times and sensor off times. The on/off state of the magnetic field sensors may be controlled by either a dedicated sensor controller or the data unit.


A drive unit for a motor vehicle screen wiper comprises a motor, a reduction gearbox and an electrical connector. The gearbox has a gearbox body, on which a closure plate is fastened. Electrically conductive strips are associated with the closure plate and make the electrical connections between the motor, the gearbox and the connector. The drive unit has a cover fixed on one face of the closure plate, with the connecting strips being interposed between this face and the cover, the closure plate and the cover defining between them a closed housing containing the connecting strips.

It is known from U.S. Pat. No. 5,218,255 to provide a drive unit for a motor vehicle screen wiper, the drive unit comprising a motor, a reduction gearbox having a gearbox body, and a closure plate which is fastened to the gearbox body. This closure plate includes a portion which constitutes an electrical connector, for example in the form of a socket, for receiving the associated wiring of the vehicle (i.e. for receiving a connecting element such as a plug), for the power supply of the wiper drive unit and for supplying control signals to the drive unit. The closure plate includes metallic electrical connecting strips, on which the material (generally a plastics material) of the closure plate is moulded.
The strips are therefore encapsulated in this material, with the ends of the connecting strips projecting from the closure plate. Some of these ends are formed as wiping contacts for making electrical contact with a movable electric contact member of the gearbox, while others are adapted to constitute connecting terminals for the motor, or connecting pins located within the connector. In this way the connecting strips make the electrical connections between the motor, the gearbox and the connector.
Moulding of the material of the closure plate over the connecting strips gives good insulation of the middle part of the connecting strips as regards corrosion and short circuits. However, the moulding, or encapsulating, operation is a somewhat heavy and complex one to carry out in practice. In addition, the connecting strips have a complicated form.

Wiper drive unit with a closure plate carrying electrical connecting strips


A reverse stranding apparatus for the reverse stranding of conductors. The apparatus comprises a stationary divider plate, a twisting plate rotatable in different directions, and a central element disposed between the parts, and peripheral tubes surrounding the central element, the central element and the peripheral tubes being pressed against each other at least during the twisting step of the conductors, and the conductors to be stranded being adapted to pass through at least the peripheral tubes. To allow high speeds of rotation, the peripheral tubes are connected substantially for their entire length to the central element by a substantially radial part.

A reverse stranding apparatus for the reverse stranding of conductors, such as filaments, conductor elements, bundles of conductors, optical fibres and similar for the manufacturing of cables or the like, comprising a stationary divider means disposed at the upstream end for the conductors to be stranded, a twisting means rotatable in different directions and disposed at the downstream end for the conductors to be stranded, and a medially disposed central element rotatable recurrently about its longitudinal axis in opposite directions and peripheral tubes being twistable recurrently in opposite directions and peripherally surrounding the central element, the central element and the peripheral tubes being disposed between the divider means and the twisting means and being pressed against each other at least during the twisting step of the conductors and the conductors to be stranded being adapted to pass through at least the peripheral tubes.
A wide variety of apparatus as presented above are known for instance in the cable industry. The apparatus disclosed in U.S. Pat. No. 4 974 408 may be mentioned as an example of prior art apparatus in this field. The apparatus disclosed in said U.S. Patent operates completely faultlessly in most circumstances. However, in some circumstances the operation is not the best possible. For example, it has been found in practice that with high speeds of rotation of a tube packet, centrifugal force will produce outward radial displacement of the peripheral tubes on the unbound portions thereof. In the above known solution, the peripheral tubes are bound by means of spaced elastic rings, the compression force of which acts only on a specific longitudinal area of the tubes. The axial spanning force on the tube packet and the relative distance of the elastic rings together define the maximum speed of rotation. Exceeding said speed will have the result that the outer peripheral tubes bulging outwards under the influence of centrifugal force displace the elastic rings in the axial direction, and thus with this mechanism the disruption will be self-augmenting. Also the central tube has a tendency to come out from between the peripheral tubes, if it has been stretched more than the outer peripheral tubes. Another problem is presented by creep, which is due to the properties of the plastics used as the tube material. This creep is very intense at the initial stage of putting into use the tube packet, and consequent thereon the tube packet must be shortened several times. Later said creep will diminish, but it will not cease. On account of the creep, the maximum length of the tube packet is limited, which again limits the maximum relative distance of the reversing points. A third problem worth mentioning is that the desired axial spanning force cannot be used owing to the material employed. This fact is reflected in sagging of the tube packet, which in turn will produce undesired whirling. It is known from experience that a large sag of the tube packet will increase the friction coefficient between the tube and the conductor. The plastics that are most suitable for use as tube materials typically have high friction coefficients and poor mechanical strength values. In the prior solutions, specifically the friction coefficient between the tube and the conductor is the most significant factor affecting the number of upturns in the same direction which is obtained. The intent is to achieve a maximum number of upturns in the same direction, as by this means the reversing points can be disposed far from one another, and this again improves the electrical characteristics of a telecommunications cable.
It is the object of the present invention to provide a reverse stranding apparatus wherewith the drawbacks of the prior art can be eliminated. This has been achieved with the reverse stranding apparatus of the invention, which is characterized in that the peripheral tubes are connected substantially for their entire length to the central element by means of a substantially radial part.
The advantage of the invention lies above all in that the radial connection of the tubes to the central element allows remarkably high speeds of rotation for the rotating head/tube packet. Very high grouping and stranding speeds are possible even with small upturn values. Generally speaking, it can be said that due to the invention, the tube packet will no longer limit the speed of rotation, but the limiting factor is constituted by the motor. The construction of the tube packet in accordance with the invention is safer and more durable than heretofore. At no time will the central element be able to push out from between the peripheral tubes. In the construction according to the invention, the tube packet will retain its initial longitudinal dimension for its entire service life. The axial spanning force on the tube packet can be increased many fold, thus permitting effective prevention of whirling. A smaller friction than heretofore is achieved between the tube and the conductor, since it is known from experience that the smaller the sag, the lower the friction. Thus, the length of the tube packet will not constitute a restricting factor. A further advantage is that by means of the invention, different and continuously varying run profiles of speed of rotation for the rotating head can be employed without any restrictions. The rotating head and the tube packet typically display very high speeds of rotation, continuously changing direction. A small friction between the tube and the conductor will add to the windings of the tube packet in the same direction. A better quality than heretofore is achieved for sophisticated cables. The grouping or stranding procedures do not induce any forces acting adversely on the conductor or any deformation that would stretch the conductor, for instance.

Reverse stranding apparatus with twistable peripheral tubes attached to a central element


A tabular terminal-use female terminal in which a tabular terminal is inserted is provided, which tabular terminal-use female terminal includes: a pair of elastic holding pieces extending in an insertion direction of the tabular terminal; a holding portion provided on each elastic holding piece for holding the tabular terminal; a guide face extending from each holding portion to an front end portion of each elastic holding piece for guiding the tabular terminal to the holding portion; and a receiving tapered portion provided on a side portion of each guide face, wherein the tabular terminal is able to be laterally inserted into the tabular terminal-use female terminal.

1. Field of the Invention
The present invention relates to a female terminal wherein a tabular terminal can be laterally or obliquely inserted between a pair of elastic holding pieces thereof.
2. Description of the Related Art
A relay box with a fuse is provided in an electric wiring for various electric appliances aboard a vehicle for protecting the circuit. Here, the relay box is called a fuse box, a junction block or an electric junction box. As one of the fuses to be mounted on a fuse accommodating portion of the relay box, a blade-type fuse is known. The blade-type fuse has a pair of tabular terminals which are connected with a soluble portion in an insulative housing. This blade-type fuse is inserted into in the fuse accommodating portion of the relay box. Each of two tabular terminals is inserted between a pair of elastic contact pieces of the female terminal accommodated in the relay box.
The female terminal has a terminal body 40, a wire connecting portion 41 to crimp an electric wire (not shown), and a terminal contact portion 43 as shown in FIG.6. The terminal contact portion 43 has a pair of elastic holding pieces 42. The elastic holding piece 42 is formed of a rectangular plate. The pair of elastic holding pieces 42 are put into contact with each other near front end portions thereof. Each elastic holding piece 42 has a guide portion 44 between the front end and the contact portion. That is, the vicinity of the front end portion of each elastic holding piece 42 is in an L-shape. A front end portion of a tabular terminal 2 is inserted between the guide portions 44. The tabular terminal 2 is inserted deep, and the female terminal 45 is electrically connected to the tabular terminal 2. The fuse 3 is inserted in the fuse accommodating portion. When the tabular terminal 2 of the fuse 3 is inserted into the female terminal, a longitudinal axis al of the tabular terminal 2 is normally almost in parallel with a longitudinal axis b of the female terminal as shown in FIG.7. A width direction of the tabular terminal 2 and a width direction of the elastic holding piece 42 are substantially parallel.
However, as shown in FIG. 8, the fuse 3 is sometimes laterally or obliquely inserted in the fuse accommodating portion. At this time, as shown in FIG. 9, a side face 2c of the tabular terminal 2 abuts front-end side faces of the elastic holding pieces 42. In this case, the tabular terminal 2 is not inserted between the elastic holding pieces 42. If the fuse 3 is forcibly inserted, the tabular terminal 2 is damaged.


A carrying bag comprises at least one extensible panel forming at least a part of the external walls of the bag. The extensible panel is of a composite material composed of a sheet of a stretch-knit fabric and a multiplicity of elongated strips of a durable, substantially non-extensible material joined to the fabric sheet in closely spaced relation by stitching located proximate to the centers of the strips, thereby leaving portions of the fabric sheet underlying the major portions of the strips free to stretch.

People use carrying bags to carry around all sorts of things. There are the purses and handbags of many styles and constructions that virtually all women use for innumerable articles, briefcases and portfolios that office workers use, hand luggage for travel available in a wide range of sizes and styles, and all purpose bags, which are usually soft and made of leather or a fabric. (The term "carrying bags" is used herein in a broad sense to refer to purses, handbags, briefcases, luggage, and all purpose bags, as well as other articles that serve similar purposes, such a duffle bags, backpacks, toiletry cases, money pouches and so forth.) Carrying bags are often called upon to receive more articles than they are intended to hold or bulky articles that do not quite fit into them. Many people, therefore, like to have carrying bags that can expand or deform, and "soft" carrying bags of a fabric, such as canvas, or of natural or synthetic leather are very popular. Purses, portfolios and briefcases having pleated side and end walls that expand and contract, depending on the volume of material put into them, also meet this need.
Stretchable fabrics can be used for carrying bags, but are not entirely satisfactory for at least two reasons. First, stretchable fabrics are subject to mechanical failure, such as by tearing, if they are overloaded and stretched excessively; second, they lack durability against snags and tearing from contacting other objects, abrasion over time (natural wear and tear), and soiling.


An image forming apparatus according to one aspect of the disclosure includes a printing mechanism, a drawing data creating circuit, a medium supply circuit, and a charging circuit. The medium supply circuit performs: a primary supply supplying the printing medium to a specific position; and a secondary supply supplying the printing medium from the specific position to the printing mechanism. When the band-used color fixed as color by the drawing data creating circuit exists, the medium supply circuit starts the primary supply prior to completion of creating all the bands of the drawing data by the drawing data creating circuit. When the band-used color fixed as color by the drawing data creating circuit exists, the charging circuit performs the charging process in a case where the color for use is color, in starting the primary supply.

Unless otherwise indicated herein, the description in this section is not prior art to the claims in this application and is not admitted to be prior art by inclusion in this section.
There is known an image forming apparatus that includes a printing unit, a drawing data creating unit, and a medium supply unit. The printing unit performs printing on a printing medium. The drawing data creating unit creates drawing data, which causes the printing unit to perform printing. The medium supply unit supplies the printing medium to the printing unit. This medium supply unit performs a primary supply and a secondary supply. The primary supply supplies the printing medium to a specific position. The secondary supply supplies the printing medium from the specific position to the printing unit. A typical image forming apparatus starts the primary supply prior to completion of creating the drawing data. This ensures the improved printing speed compared with a configuration that starts the primary supply after completion of creating the drawing data.

Image forming apparatus that improves printing speed and recording medium


Provided is a higher quality aptamer having a binding activity to NGF.

Nerve growth factor (NGF) is the first neurotrophin identified in 1951, and is an important secretory protein involved in the development and survival of peripheral and central neurons. It consists of 118 amino acids, has a molecular weight of 13 kDa, and has S—S bonds at 3 positions in a molecule. BDNF, NT-3 and NT-4/5 are present in the family protein, which are structurally well conserved and form a homodimer by a noncovalent bond. It has a β sheet structure facing 3 different directions, and is considered to be dimerized in this part. It also has four loop structures with low homology among families, and these parts are considered to define specificity to receptors.
As NGF receptors, tyrosine kinase-type receptor TrkA with high affinity and p75 with low affinity which belongs to a tumor necrosis factor receptor superfamily are known. These receptors act as a homodimer or heterodimer and are deeply involved in the development and maintenance of the nervous system. TrkA is a single-pass transmembrane receptor and has a tyrosine kinase structure in the intracellular domain. When NGF is bound, tyrosine phosphorylation occurs, the signal is transmitted to the downstream, and promotion of differentiation and survival maintenance of the cell occur.
As family receptors of TrkA, TrkB and TrkC are known. TrkB is bound to BDNF and NT-4/5, and TrkC is bound to NT-3. p75 shows lower ligand specificity as compared to TrkA and is also bound to BDNF, NT-3 and NT-4/5 besides NGF. While p75 is a single-pass transmembrane receptor, it does not have a tyrosine kinase domain on the cytoplasmic side. Like TrkA, it is expressed not only in nerve cells but also in non-nerve cells. This receptor is known to be involved in the promotion of differentiation and survival maintenance of the cell, as well as related to the induction of apoptosis and cell migration. The results of crystal structure analysis have suggested that an NGF homodimer binds to TrkA at 2:2 and to p75 at 2:1. An NGF homodimer sometimes binds to a heterodimer of TrkA and p75.
NGF is produced by Schwann cell, keratinized cell, bronchial epithelial cell, fibroblast, T lymphocyte, macrophage, mast cell, B lymphocyte, keratinocyte, smooth muscle cell, renal glomerular cell, skeletal muscle cell and the like. On the other hand, TrkA is known to be expressed in nerve cell, as well as monocyte, T lymphocyte, B lymphocyte and mast cell other than nerve cell. Similarly, p75 is expressed in nerve cell as well as non-nerve cells.
It is well known that NGF plays a key role in the nervous system. It has been clarified that NGF has an action to maintain survival of cholinergic neuron and is considered to be related in some way to Alzheimer's disease. In addition, since intracerebral administration of NGF improves memory disorders of old rats, it is also expected as a therapeutic drug for senile dementia.
It has been found that NGF also acts on the tissues and cells other than the nervous system, and involved in the body's defense and tissue repair process. For example, it is known that administration of NGF to an animal increases blood vessel permeability, enhances immune responses of T cell and B cell, induces differentiation of lymphocytes, induces growth of mast cells, induces release of various cytokines from mast cells and the like.
NGF is related to inflammation, and increased expression of NGF has been observed in patients with inflammatory diseases and inflammatory animal models. Systemic lupus erythematosus, multiple sclerosis, psoriasis, arthritis, interstitial cystitis, asthma and the like are the examples thereof. It has been reported that the synovial fluid of patients with rheumatoid arthritis shows higher NGF concentration. In addition, increased NGF expression in rheumatoid arthritis model rats, and increase in mast cells and increased NGF expression in arthritis model mouse have been reported.
NGF is deeply involved in pain. When NGF is subcutaneously administered to human, a deep pain such as muscular pain continues for several days, and hyperalgesia of the injection site occurs. NGF knockout mouse and TrkA knockout mouse lacks unmyelinated nerve and do not feel pain. When NGF is intraperitoneally administered at 1 mg/kg to a mature rat, hyperalgesia against noxious heat and mechanical stimuli occurs. NGF transgenic mouse shows hyperalgesia unaccompanied by inflammatory conditions. In addition, it is known that the TrkA gene of patients with congenital insensitivity to pain with anhidrosis (CIPA) has abnormality, and pain sensation decreases when NGF gene has abnormality.
From the above, an NGF inhibitor can be used as a therapeutic drug for pain such as nociceptive pain, inflammatory pain, neuropathic pain, carcinomatous pain, fibromyalgia pain and the like. A combination therapy of NGF antibody and NSAID (Patent reference 1), a combination therapy of NGF antibody and opioid analgesic (Patent reference 2), a treatment method of postsurgical pain using an NGF antibody (Patent reference 3, Patent reference 4), a treatment method of pain of bone cancer using an NGF antibody (Patent reference 5), and a treatment method of pain of osteoarthritis using an NGF antibody (Patent reference 6) have been reported.
Tanezumab (PF-4383119 or RN624) is an antibody against NGF, shows effect in pain model experiment using an osteoarthritis animal model, and is currently under clinical trial. While the presence or absence of inhibitory activity of NGF and NGF receptor is unknown, there is a report relating to natural RNA that binds to NGF (non-patent document 1).
In recent years, applications of RNA aptamers to medicaments, diagnostic agents, and test drugs have been drawing attention; some RNA aptamers have already been in clinical study stage or in practical use. In December 2004, the world's first RNA aptamer drug, Macugen, was approved as a therapeutic drug for age-related macular degeneration in the US. An RNA aptamer refers to an RNA that binds specifically to a target molecule such as a protein, and can be prepared using the SELEX (Systematic Evolution of Ligands by Exponential Enrichment) method (Patent references 7-9). In the SELEX, an RNA that binds specifically to a target molecule is selected from an RNA pool with about 1014 different nucleotide sequences. The RNA structure used has a random sequence of about 40 residues, which is flanked by primer sequences. This RNA pool is allowed to be assembled with a target substance, and only the RNA that has bound to the target substance is collected using a filter and the like. The RNA collected is amplified by RT-PCR, and this is used as a template for the next round. By repeating this operation about 10 times, an RNA aptamer that binds specifically to the target substance can be acquired.
Aptamer drugs, like antibody drugs, can target extracellular factors. With reference to many scientific papers and other reference materials in the public domain, aptamer drugs are judged to potentially surpass antibody drugs in some aspects. For example, aptamers often show higher binding force and higher specificity than do antibodies. Aptamers are unlikely to undergo immune elimination, and adverse reactions characteristic of antibodies, such as antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC), are unlikely to occur with the use of aptamers. From the aspect of delivery, since aptamers are about 1/10 of antibody in size, delivery of a drug to the object site is easier. Since aptamers are produced by chemical synthesis, various modifications can be made easily, reduction of cost by large-scale production is possible. Meanwhile, the blood half-lives of aptamers are generally shorter than those of antibodies; however, this property is sometimes advantageous in view of toxicity. These facts lead to the conclusion that even when the same molecule is targeted, aptamer drugs potentially surpass antibody drugs.
The present inventors have produced, in PCT/JP09/066,457, an aptamer which binds to NGF and inhibits binding of NGF and an NGF receptor, and found that the aptamer inhibits a neurite outgrowth activity of NGF. Patent document 10 describes an aptamer to NGF, which is obtained by automated SELEX, and patent document 11 describes an altered product and a modified product of the aptamer obtained in patent document 10.

Abstract: An aptamer binding to NGF, which satisfies the following (1) and (2):    (1) containing the sequence represented by UGAAARAAACC (SEQ ID NO: 64) or CGAAMRAAACU (SEQ ID NO: 65), and    (2) having a base length of not more than 73.


A personalized postal stamp has on a back surface thereof an adhesive layer for adhering the stamp to a letter or postal card, and on a front surface thereof first and second regions. The first region presents an image of indicia qualifying the stamp as a lawful stamp of a given postage denomination, and the second region, which is substantially disposed within the first region, presents an image of a person who purchased the stamp from a vending machine. The front surface is of unitary, one-piece and integral construction. The first and second region images are formed either simultaneously in a single operation or at different times by different operations.

The present invention relates to a personalized postal stamp and a method of making the same, and more particularly to such a stamp and method wherein the front surface of the stamp is of unitary, one-piece and integral construction for acceptability to the Postal Service.
The desirability of a personalized postal stamp--that is, a stamp bearing on the front surface thereof both the indicia qualifying the stamp as a lawful stamp of a given postage denomination and an image of a person who was in a predetermined spatial relationship to a vending machine at the time the stamp was purchased--is well known and has resulted in several patents relating thereto. Notwithstanding the flurry of past inventive concepts that were deemed worthy of the issue of a U.S. patent thereon, to the best of Applicant's knowledge neither the U.S. Post Office nor the U.S. Postal Service (i.e., the U.S. Postal Authorities) has ever authorized such a personalized postal stamp for use in the postal system.
For the most part, the pertinent prior art inventive concepts involved providing on the front surface of the stamp a first region presenting an image of indicia qualifying the stamp as a lawful stamp of a given postage denomination, and a second blank region substantially disposed within the first region, and further involved providing photographs of an individual, suitably cropped to fit within the second region. The stamp contains on the back surface an adhesive layer for adhering the stamp to a letter or postal card. Either the photograph includes on the back surface an adhesive layer for adhering the photograph on the second region, or the user of the stamp is intended to apply an adhesive layer between the photograph and the second region so as to secure together the back surface of the photograph and the front surface of the second region. See, for example, U.S. Pat. No. 5,423,573, which describes both regions as having adhesive backs so that the decorated design or photograph may be adhered to the front face of the stamp and the stamp adhered to the letter or postal card.
It is the belief of the inventor that the primary reason the aforementioned prior art inventive concepts have not materialized is because the postal authorities would not accept a stamp having an adhesively affixed photograph thereon because it might interfere with or otherwise render unreliable the stamp cancellation process. A stamp is generally of a relatively small size, and the photograph would preferably be designed to occupy a major portion of the stamp so that the photographic image would be recognizable. Typically a stamp is cancelled by receiving a cancellation imprint over the stamp. The cancellation imprint may simply be a series of parallel wavy lines extending over at least some portion of the stamp and optionally at least some portion of the letter or postal card thereabout. To the extent that the cancellation imprint was substantially contained on the photograph, in the inventive concepts discussed above the photograph (and therefore substantially all of the cancellation imprint) could be removed from the used stamp and the stamp then reused. Alternatively, in the same situation a second photograph could be adhered to a used stamp (over the first photograph) to conceal the cancellation imprint, and the stamp then reused. Reuse of the stamp could be either without any photograph or with a replacement photograph. In both instances, at least a substantial portion of the cancellation imprint would be either removed or concealed, thus possibly enabling unlawful reuse of the stamp without detection.
Accordingly, it is an object of the present invention to provide a personalized postage stamp which may be more acceptable to the postal authorities than the prior art personalized postage stamp concepts.
Another object is to provide such a stamp which would not lend itself to unlawful reuse after receipt of a cancellation imprint.
A further object is to provide a method of making such a stamp.
It is also an object of the present invention to provide a vending machine for making and selling such a stamp.


This invention relates to an improved adhesive composition having extended holding power accompanied by adhesion building properties during use and having increased gel adhesion, which composition consists essentially of (a) from about 10 to about 35 wt. % lower alkyl vinyl ether-maleic acid copolymer wherein from 0 to about 90 wt. % of the copolymer carboxyl units are converted to a mixture of salts selected from the group of calcium, sodium, strontium, zinc, magnesium and potassium; (b) a crosslinked non-ionic natural guar gum in a mole ratio of between about 0.75:1 and about 5:1 with respect to the copolymer; and (c) from about 30 to about 70 wt. % oil base as a carrier. The invention also relates to the preparation and use of said adhesive for affixing dentures.

Various adhesive compositions have been employed for affixing dentures or ostomy devices to mucus membranes, several of which involve the use of methyl vinyl ether-maleic acid metal salts as disclosed in U.S. Pat. Nos. 3,003,988; 3,833,518; 3,868,339; 4,758,630; 4,183,914; 4,217,342, 4,217,343 and 5,093,387. U.S. Pat. No. 5,093,387 additionally proposes the use of the above mixed salts with an cationic gum, such as a synthetic guar gum salt. However, such denture adhesive compositions containing the copolymeric salts and/or cationic thickeners are found to be effective for only a limited time of not more than 8 hours and, in some instances, for as little as only 2-3 hours.
Accordingly it is an object of this invention to provide an improved adhesive composition which not only possesses extended holding power but also builds viscosity during use.
Another object is to provide an improved adhesive composition which is economical, easily prepared and which can be readily processed in commercial blending equipment.
These and other objects of this invention will become apparent from the following description and disclosure.


A watch system is provided, including a watchband, a lug bucket, and a puck. The watchband may include a flexible member configured to be mounted onto a wrist of a user. The lug bucket may be coupled to the electronic watch band and may include a circular ledge. The puck may include watch functionality. The puck may be configured to be removably coupled to the lug bucket. The lug bucket and the puck may have corresponding locking features that are configured to rotationally and translationally fix the puck to the lug bucket. The corresponding locking features may be configured to be engaged when the puck is translated relative to the lug bucket and rotated relative to the lug bucket by a predetermined rotation angle.

Conventional watches and smartwatches permit changing the watchband at the lugs (i.e., projections on the watch casing that couple to the watchband) to customize the material and the color of the watchband. However, such conventional watches and smartwatches typically limit the number of lug styles that are possible, and changing the material or the color of the watch casing is usually not permitted. For such conventional watches and smartwatches, many different stock keeping units ("SKUs") would be needed in order to permit the user to select the material or the color of the watch casing, which may be costly and may require complicated inventory control.

Bayonet mechanism for interchangeable lug and band styles


The present invention provides isolated peptides or the fragments derived from SEQ ID NO: 42, which bind to an HLA antigen and induce cytotoxic T lymphocytes (CTL). The peptides may include one of the above mentioned amino acid sequences with substitution, deletion, or addition of one, two, or several amino acids sequences. The present invention also provides pharmaceutical compositions including these peptides. The peptides of this invention can be used for treating cancer.

It has been demonstrated that CD8-positive CTLs recognize epitope peptides derived from tumor-associated antigens (TAAs) on the major histocompatibility complex (MHC) class I molecule, and then kill the tumor cells. Since the discovery of melanoma antigen (MAGE) family as the first example of TAAs, many other TAAs have been discovered through immunological approaches (NPLs 1, 2), and some of these TAAs are now in the process of clinical development as immunotherapeutic targets.
Favorable TAA is indispensable for proliferation and survival of cancer cells, as a target for immunotherapy, because the use of such TAAs may minimize the well-described risk of immune escape of cancer cells attributable to deletion, mutation, or down-regulation of TAAs as a consequence of therapeutically driven immune selection. Accordingly, the identification of new TAAs capable of inducing potent and specific anti-tumor immune responses warrants further development and thus clinical application of peptide vaccination strategies for various types of cancer is ongoing (NPLs 3 to 10). To date, several clinical trials using these TAA derived peptides have been reported. Unfortunately, many of the current cancer vaccine trials have shown only a low objective response rate (NPLs 11 to 13). Accordingly, there remains a need for new TAAs as immunotherapeutic targets.
The TOMM34 gene (GenBank Accession No. NM_006809), translocase of outer mitochondrial membrane 34, has been identified from human EST and cDNA databases and predicted to encode a protein containing degenerated tetratricopeptide repeat (TPR) motifs (NPL 14). The protein encoded by this gene is involved in the import of precursor proteins into mitochondria. This protein has a chaperone-like activity, binding the mature portion of unfolded proteins and aiding their import into mitochondria (NPL 15).
In a recent study, it was indicated that TOMM34 is frequently up-regulated in colorectal cancer by gene-expression profile analysis using cDNA microarray consisting of 23040 genes. Furthermore, knockdown of TOMM34 by siRNA in colon cancer cell lines attenuated the growth of colon cancer cells (NPL 16).

TOMM34 peptides and vaccines including the same


A positive displacement inductive pump which includes a pair of steel cylinders or sleeves having a non-magnetic corrosion resistant inner surface and non-magnetic alloy rings disposed at each cylinder end. Three ferromagnetic pole pieces having an axial opening are provided with each cylinder disposed between a respective pair of the pole pieces and connected to the pole pieces with the alloy rings. A pair of oppositely disposed steel plates connected to the pole pieces forms a magnetically conductive circuit between the pole pieces. A piston positioned within the bore defining a displacement chamber adjacent to each end of the bore. The piston includes a rod formed of magnetic material with a corrosion resistant lining encapsulating the rod. The pistons outer lining surface forms a seal with the material on the inner surface of the cylinders. Respective inductive coils are wound around each cylinder and are alternatingly energized to produce magnetic fields which cause the piston to move to oppositely located ends of the bore. Respective check valve assemblies are attached to each outer pole piece at the ends of the bore. The check valve assemblies allow for the ingress and egress of material into and out of the associated adjacent displacement chamber dependent upon the directional movement of the piston.

The present invention relates to an improved positive displacement inductive pump. More particularly, the present invention relates to an improved positive displacement conductive pump of the type disclosed in the parent application.
The conductive pump disclosed in the parent application, essentially comprises a piston formed of magnetic material which is disposed within a bore for movement therein as a result of magnetic fields applied to the piston to move same back and forth within the bore. Each of the two ends of the bore is generally closed off by a respective check-valve assembly which permits ingress and egress to the respective displacement chambers formed at the respective ends of the bore. Reciprocal movement of the piston is provided by a magnetic field produced by coils surrounding the bore and to the piston via a magnetic circuit. The pump described in the parent application is particularly suited for use in corrosive atmospheres by providing the piston with a non-magnetic sheath of a corrosion resistant material and by forming the bore in a nonmagnetic corrosion resistant housing, with a seal being formed between the outer surface of the piston and the wall defining the bore. To improve the transfer of the magnetic energy from the coils to the piston, a novel magnetic circuit wit a frame construction is provided.
Although the pump according to the parent application generally operates satisfactorily for its intended purpose, it is desirable to provide for increased pressure for the pump by further increasing the magnetic energy transfer efficiency, as well as to manufacture the pump in a more economical manner. It is therefore the object of the present invention to provided an improved positive displacement inductive pump that not only contains the corrosion resistant and energy transferring features according to the parent application, but moreover can provide a further increased magnetic power transfer to the piston and can be manufactured in a more robust and inexpensive manner.

Electromagnetic pump with magnetically separated cylinders


Technologies for secure device configuration and management include a computing device having an I/O device. A trusted agent of the computing device is trusted by a virtual machine monitor of the computing device. The trusted agent executes an attestation algorithm to generate a first secure attestation for the first I/O device and a second secure attestation for the second I/O device, obtains a peer-to-peer communication key, and forwards the peer-to-peer communication key to the first I/O device and a second I/O device to enable secure peer-to-peer communication between the first I/O device and the second I/O device over a communication link secured by the peer-to-peer communication key. Other embodiments are described and claimed.

Current processors may provide support for a trusted execution environment such as a secure enclave. Secure enclaves include segments of memory (including code and/or data) protected by the processor from unauthorized access including unauthorized reads and writes. In particular, certain processors may include Intel® Software Guard Extensions (SGX) to provide secure enclave support. In particular, SGX provides confidentiality, integrity, and replay-protection to the secure enclave data while the data is resident in the platform memory and thus provides protection against both software and hardware attacks. The on-chip boundary forms a natural security boundary, where data and code may be stored in cleartext and assumed to be secure. Intel® SGX does not protect I/O data that moves across the on-chip boundary.
Modern computing devices may include general-purpose processor cores as well as a variety of hardware accelerators for offloading compute-intensive workloads or performing specialized tasks. Hardware accelerators may include, for example, one or more field-programmable gate arrays (FPGAs), which may include programmable digital logic resources that may be configured by the end user or system integrator. Hardware accelerators may also include one or more application-specific integrated circuits (ASICs). Hardware accelerators may be embodied as I/O devices that communicate with the processor core over an I/O interconnect.
Accelerator devices typically communicate directly with the host device. However, certain types of accelerator devices also need to communicate directly with each other (peer-to-peer accelerator communication). This form of peer-to-peer accelerator communication is emerging especially on certain machine learning accelerators.
In the context of trusted execution, when multiple accelerators need to directly communicate with each other, it is important to ensure that only accelerators that are within the same trust boundary are able to access each other's data. If this security guarantee is not met, then a malicious accelerator running in a completely different trust domain could send malicious messages to other accelerators without detection or extract sensitive data out of them.

Secure accelerator device pairing for trusted accelerator-to-accelerator communication


A cell culture apparatus includes a housing, a bag and an inflatable bladder. The bag is disposed in the housing and has an interior surface defining a chamber for culturing cells. The bladder is disposed in the housing, external to the bag, and is sufficiently inflatable and expandable to exert pressure on the bag when the chamber is substantially free of fluid. The bladder may be inflated and expanded to reduce movement of the bag within the housing. Alternatively, or in addition, the bladder may be inflated and expanded to apply a mechanical stress on cells cultured within the chamber of the bag.

Cell culture vessels containing flexible, bag-type cell culture chambers can be difficult to manipulate if they are not supported by a rigid housing. If the flexible, bag-type cell culture chambers are supported by a tight-fitting rigid housing, the housing must also adjust to accommodate the expanding bag as it fills. If the housing is constructed so that it has a fixed capacity, then an under-filled bag will be free to move about within the housing during transport or other manipulations.
Growing large numbers of attachment dependent cells in bag-like cell culture devices is very difficult because the bags are inherently flexible. This characteristic compromises the ability of the cells to attach and decreases the possibility that the vessel can be manipulated robotically. To grow large numbers of cells, a large surface area is needed. Increasing the surface area of a bag-like device complicates handling. Stacking several smaller bag-like vessels typically requires a separate unit with shelves upon which the vessels can be supported. If the vessels are stacked to form an integral unit, a fixed volume is usually necessary to provide a rigid support. This abolishes the variable-volume benefit of having a bag-like device.
Most cell types may be cultured in bag-like cell culture devices. For example, cells such as cardiac, lung, muscle, bone and cartilage cells may be culture in such devices. Such cells when grown in vitro under conditions where some type of mechanical stress is applied to the cultured cells, differentiate to phenotypically resemble their in vivo counterparts. Without such an applied stress, such cells typically require soluble factors to differentiate. To induce differentiation via mechanical stress and strain, many researchers cobble together their own devices to provide the physical stimulus required to encourage cells to differentiate along a particular lineage. Commercially available devices for application of mechanical stress and strain tend to be very precise and limited to very small numbers of cells in culture.


In a telecommunications system interconnection is made between a broadband network and a narrowband PABX by an interworking unit providing conversion between the cell based switching of the broadband network and the circuit switching of the narrowband PABX, whereby broadband network users have access to PABX telephony facilities. The broadband network may be ATM based.

The present invention relates to an interworking unit for use on a broadband campus network which will interconnect the broadband network with a narrowband PABX. The unit will provide conversion between the cell based switching of the broadband network and the 64 Kbit circuit switching of the narrowband PABX. In order to enable the broadband users to have access to the normal PABX style telephony facilities, the interworking unit will adapt the broadband signalling to narrowband signalling.
A basic block diagram of a typical system is shown in FIG. 1.

Siemens GEC Communication Systems Limited


A charging device includes magnetic particles, a magnetic particle carrying member that magnetically carries the magnetic particles into contact with a member to be charged, and a magnetic particle adjusting unit for adjusting an amount per unit area of magnetic particles carried on the magnetic particle carrying member so that the amount per unit area of magnetic particles carried is larger in end regions of the magnetic particle carrying member in the longitudinal direction than in a central region of the magnetic particle carrying member in the longitudinal direction.

1. Field of the Invention
The present invention relates to charging devices with magnetic particles.
2. Description of the Related Art
Many image-forming apparatuses based on electrophotography or electrostatic recording have conventionally been created. The schematic structure of such an apparatus and its operation are briefly described below with reference to FIG. 2.
When a copy-start signal is input to an image-forming apparatus shown in FIG. 2, a corona charging device 3 charges the surface of a photosensitive drum 1 to a predetermined potential. In addition, an integral unit 9, which includes a document-illuminating lamp, a short-focus lens array, and a CCD sensor, illuminates and scans an original document G placed on a document table 10. The scanning light is reflected off the document surface and is focused by the short-focus lens array to enter the CCD sensor, which has a light-receiving part, a transfer part, and an output part. The light signals entering the CCD sensor are converted into charge signals in the light-receiving part. The charge signals are then synchronized with clock pulses in the transfer part, are sequentially transferred to the output part, are converted into voltage signals in the output part, are amplified with reduced impedance, and are output to the outside as analog signals. The resultant analog signals are converted into digital signals by known image processing, and are transferred to a printer section. In the printer section, an LED exposure device 2 is turned on/off in response to the above image signals to emit light which forms an electrostatic latent image corresponding to an image of the original document G on the surface of the photosensitive drum 1.
A developing device 4 containing toner particles develops the electrostatic latent image into a toner image on the photosensitive drum 1. A transfer device 7 electrostatically transfers the toner image onto a transfer material which is then electrostatically separated and carried to a fusing device 6. The toner image is thermally fused onto the transfer material to output the image.
After the toner image is transferred, a cleaner 5 removes contaminants adhering to the surface of the photosensitive drum 1, including toner residue after the transfer. In addition, if necessary, the photosensitive drum 1 is exposed to light by a pre-exposure device 8 to eliminate the optical memory of the image exposure for repeated use in image formation.
Conventionally, charging devices for use in an image-forming process with an electrophotographic image-forming apparatus as described above are typically based on corona charging, as mentioned above. In recent years, however, contact charging has been intensively researched and developed, and has already been put into practical use. Contact charging has the advantages of yielding a small amount of ozone by discharge and low power consumption.
In contact charging, a charging member is brought into contact with a photosensitive member and is supplied with voltage to charge the photosensitive member. Examples of charging devices based on this method include charging rollers and magnetic brush charging devices. Among them, a magnetic brush charging device, in which a magnetic brush serves as a contact charging member, is used to achieve contact charging stability.
A magnetic brush charging device magnetically holds conductive magnetic particles directly on the surface of a magnet or on the surface of a sleeve including the magnet. The magnetic particles are brought into contact with the surface of a photosensitive member to charge the surface of the photosensitive member.
When a magnetic brush charging device is used to charge, for example, an organic photosensitive member having a surface layer in which fine conductive particles are dispersed (according to, for example, Japanese Patent Laid-Open No. 06-003921, which corresponds to U.S. Pat. No. 5,809,379) or an amorphous-silicon-based photosensitive member, the surface of the photosensitive member can be charged to a potential substantially equivalent to the DC component of a bias applied to a magnetic brush. Such a charging method is hereinafter referred to as magnetic brush injection charging. This method involves no discharging phenomenon as used in contact charging to provide ozone-free charging with low power consumption.
Unfortunately, however, a photosensitive member of an image-forming apparatus including a magnetic brush injection charging device has a shorter life than that of an image-forming apparatus including a corona charging device. The surface of the photosensitive member wears by friction against magnetic particles after repeated use. This problem is more serious when a sleeve and the photosensitive member are rotated in opposite directions to increase the possibility of contact between the magnetic particles and the photosensitive member for higher charging stability.
The life of the photosensitive member can be significantly increased by making a modification to the photosensitive member, such as a hard protective layer provided on the surface of the photosensitive member, or a modification to the charging device, such as the coating of the magnetic particles and the reduction of the pressure between the magnetic particles and the photosensitive member for lower friction against the magnetic particles.
The pressure between the magnetic particles and the photosensitive member can be reduced by, for example, extending the distance between the sleeve and the photosensitive member or reducing the amount of magnetic particles carried on the sleeve. Such approaches, however, also have adverse effects such as insufficient contact between the magnetic particles and the photosensitive member. This results in reduced charging stability and the adhesion of the magnetic particles from the sleeve to the photosensitive member.
The most serious effect among the adverse effects is the adhesion of the magnetic particles to the photosensitive member at the outermost ends of a magnetic particle carrying region of the sleeve. Magnetic particles adhering to the photosensitive member may undesirably intrude into a developing device to degrade image quality, cause transfer defects in a transfer device, and damage the photosensitive member at a cleaner.
The adhesion of the magnetic particles to the photosensitive member at the outermost ends of the magnetic particle carrying region of the sleeve results from an unstable magnetic particle carrying state. Such an unstable state occurs probably because the magnetic force of the magnet included in the sleeve is weak at the ends of the sleeve. In addition, the contact between the magnetic particles and the photosensitive member is poorer at the outermost ends of the sleeve than the center thereof. The photosensitive member is therefore insufficiently charged at the outermost ends of the sleeve to produce a potential difference between the sleeve and the photosensitive member. This potential difference can cause the magnetic particles to adhere to the photosensitive member. Some methods, including the insulation of the ends of the sleeve, have been proposed to prevent the problem of the potential difference between the sleeve and the photosensitive member.
If, additionally, the pressure between the magnetic particles and the photosensitive member is reduced to inhibit the wear of the photosensitive member, the magnetic particle carrying state becomes unstable at the ends of the magnetic particle carrying region of the sleeve. This is more likely to result in an insufficient effect of preventing the magnetic particles carried at the ends of the sleeve from adhering to the photosensitive member.


A Brownfields investment vehicle, and a system and method for investing in Brownfields projects are provided that are capable of supporting a Brownfields project, while reducing the investors' exposure to the associated environmental liability. The Brownfields fund makes, for example, participating capital investments, each of which may be in the form of a tranched or untranched Brownfields Value Contract (“BVC”) to a “special purpose vehicle” for a specific Brownfields project according to fund investment criteria determined by a fund manager. Each capital investment, or a portion thereof may be secured with a lien on the future cash flows and/or a portion or all of a Brownfields associated with the project. An investor's exposure to environmental liability from the projects is reduced, because the fund is completely passive with respect to the projects, despite the existence of liens on at least some of the capital investments provided by the Brownfields fund.

For many years, contaminated properties have been considered a current and future liability to their owners (current and future), and to the communities in which they are located. The market value of real property is directly affected by contamination and pollution. Valuation of real property is negatively effected by risks that are not quantifiable in terms of time and/or money. Valuation affects decision making during cleanup of contaminated property, and, likewise, decision making during remediation affects valuation, of the contaminated property and surrounding properties. The result has been that many of these properties are idle and abandoned in spite of their potential value.
"Brownfields" generally includes real properties in a contaminated or stigmatized condition. Brownfields may include, for example, abandoned, idle or under-utilized sites, urban, rural, industrial or non-industrial real property where development, expansion or redevelopment is complicated by real or perceived contamination. In contrast, "Greenfields" are undeveloped properties located mainly in suburban or rural areas. Fear of contamination is one factor that may steer real estate development to Greenfields, with unintended but nonetheless undesirable consequences such as urban sprawl, habitat destruction or loss of land suitable for agriculture.
Conversely, redevelopment of Brownfields is expected to create economic opportunities through physical improvements, job creation, tax revenues and improved urban planning. Additionally, by redeveloping Brownfields, Greenfields, including, for example, agricultural land, may be preserved and further deterioration of urban cores can be minimized. There is also a substantial unmet need for private investment (e.g., debt, equity and hybrid investments) in Brownfields remediation. This is primarily due to the exposure (or fear of exposure) by investors to environmental liability.
The Environmental Protection Agency's (the "EPA") Environmental Financial Advisory Board (the "EFAB") spend two years researching issues related to financing Brownfields remediation, and issued five reports. The EFAB's core conclusion, set forth in a published letter dated May 31, 1997, from Robert O. Lenna and John C. Wise to EPA Administrator Carol M. Browne, was "wide-scale and long-term success of Brownfields redevelopment must be sustainable in the private sector." However, there continues to be relatively few capital sources for these projects due to the perceived risk. The risk includes:                (1) financial risk, either because the environmental risk is unknown or because it is difficult to measure; and        (2) liability associated with environmental risk, including liability for past effects of contamination (lender liability) and liability of borrowers from noncompliance that could affect their ability to meet financial obligation and the value of the collateral.
There is public acknowledgment and support for the need for private investment in Brownfields remediation. The EPA has now attenuated previous, more burdensome requirements, and has developed risk-based criteria for cleanup to allow the cleanup levels to be based in part on the future use of land, which is directly related to the potential for exposure to contaminants of concern.
In a report dated December 1997, the EFAB stated the following:                In virtually every Brownfields project scenario, the absence of a viable redevelopment project results in the perpetuation of two environmentally undesirable trends: (1) urban decay (environmentally, and further deterioration of existing taxpayer-paid infrastructure, and lack of economic opportunity for nearby residents); and (2) destruction of "Greenfields" to build development that could locate on Brownfields sites.        In our view, those two undesirable trends are not sustainable in the long term as a matter of national environmental or economic policy. We believe that requiring clean-ups to meet appropriately-protective risk-based standards will both: (1) protect the public health and the environment; and (2) help to avoid the perpetuation of those two environmentally undesirable trends.
In addition to risk-based cleanup criteria, public support for Brownfields remediation exists in the Taxpayer Relief Act of 1007. Under this Act, a taxpayer may be able to deduct qualified remediation expenses incurred to clean up properties in several targeted areas. Moreover, taxpayers meeting the requirements of the Taxpayer Relief Act of 1997 are eligible to fully deduct Brownfields cleanup costs in the year in which the costs are incurred, rather than capitalizing and amortizing the costs over several years.
Moreover, certain recent revisions to the Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA) are aimed at protecting passive investors. In particular, CERCLA Section 101(20)(A) contains a secured creditor exemption which eliminates certain liability for lenders who hold indicia of ownership in a Brownfields facility primarily to protect their security interest in that facility, provided they do not participate in management of the facility.
Despite the widespread public acknowledgment of the need for large private investment in Brownfields remediation, and despite the public support for such private investment in the form of rational environmental regulation and tax incentives, there is no useful method or vehicle for large-scale, long-term investment in Brownfields remediation. Conventional private investment in remediation of Brownfields includes only small funds investing on a project-by-project basis, with the quantity of capital available being small in relation to the remediation and development cost of the project financed. Because the remediation costs of individual projects financed is often so large in relation to the type of funds available, the investment risks are large, for financing the cleanup phase, and the cost of capital, therefore, high and the success of the process may be dependent upon the market for the land and development subsequent to clean up, increasing the risk. Moreover, the legal and financing phases are long and expensive. Financial failure of a single project in such a financial model is a disaster for all of the investors. However, if the ultimate development of the property is also considered, the cost of remediation becomes economically feasible in relation to the long-term value.
Moreover, environmental remediation liability, i.e., the legal duties under applicable federal, state and local statutes and regulations regarding environmental liabilities, may attach not only to the owners of the Brownfields, but also to "operators." Operators may include, for example, lenders and others who participate in decision making regarding the Brownfields. Thus, lenders investing in properties needing remediation can themselves become liable for remediation costs if lenders take mortgages to secure their loans. This risk of direct exposure to environmental remediation liability further chills investor interest and increases the cost of privately-financed remediation of Brownfields. Thus, historically, only a small number of investors were able and willing to invest privately in projects involving Brownfields remediation and they expect high returns relative to the risk. This capital cost is another barrier to the feasibility of these projects.
Because of the traditional high risks associated with Brownfields remediation investment, few vehicles exist for such investment. Moreover, few managers have developed expertise sufficient to administer the few such investment vehicles that do exist. There are approximately 5000 registered professional investment advisors for management of a wide variety of investments in stocks, stock portfolios, bonds, and stock and bond funds. There are only a few dozen registered professional real estate investment managers, and only a handful of these managers control the majority of the market (75%). These managers offer very traditional pure equity, first mortgage and participating mortgage products not suited to the this type of investment. However, this investor base is the best source for long term capital.
With few sources of investment capital available for financing Brownfields remediation, Brownfields' owners must often rely on their own financial resources to provide the funds for remediation. These owners include most major industrial corporations, family owned businesses, government entities, farmers, developers and many others. This further constrains resources available to the ongoing business interests of these owners, and therefore, redevelopment is delayed indefinitely.
Moreover, real estate developers typically encounter substantial project delays with attendant costs because there is no single mode of financing that will cover all phases (e.g., acquisition, entitlement, development and construction) of a project. Developers must first arrange financing for acquiring the property and developing plans and designs. The project then typically halts for weeks or months while the developer arranges construction financing. Near the end of the construction phase, the project may be effectively halted again while the developer seeks and arranges permanent financing or sells the project. All three stages of financing are typically provided by separate sources, and financing fees may be required in connection with each stage of financing. Thus, there is a substantial need for a single source of financing to address all stages of a real estate project to lower the cost of capital and facilitate faster completion of a projection. This will also make projects that are not feasible today become feasible including redevelopment of Brownfields.
Furthermore, the three stages of financing are typically carried as full debt on the developer's balance sheet. Carrying environmental project-related debt on the balance sheet reduces the developer's and/or owner's equity, and, therefore, reduces the developer's and/or owner's ability to borrow funds for new projects, expansion, or to support normal operations. Accordingly, there is a need for a method of financing real estate development without reducing a developer's equity or borrowing power ("off balance sheet" financing and/or investment).

This patent is subject to a terminal disclaimer.


A vascular implant formed of a compressible foam material has a compressed configuration from which it is expansible into a configuration substantially conforming to the shape and size of a vascular site to be embodied. Preferably, the implant is formed of a hydrophobic, macro porous foam material, having an initial configuration of a scaled-down model of the vascular site, from which it is compressible into the compressed configuration. The implant is made by scanning the vascular site to create a digitized scan data set; using the scan data set to create a three-dimensional digitized virtual model of the vascular site; using the virtual model to create a scaled-down physical mold of the vascular site; and using the mold to create a vascular implant in the form of a scaled-down model of the vascular site. To embolism a vascular site, the implant is compressed and passed through a micro catheter, the distal end of which has been passed into a vascular site. Upon entering the vascular site, the implant expands in situ substantially to fill the vascular site. A retention element is contained within the micro catheter and has a distal end detachably connected to the implant. A flexible, tubular deployment element is used to pass the implant and the retention element through the micro catheter, and then to separate the implant from the retention element when the implant has been passed out of the micro catheter and into the vascular site.

Not applicable
The present invention relates to the field of methods and devices for the embolization of vascular aneurysms and similar vascular abnormalities. More specifically, the present invention relates to (a) an expansible vascular implant that is inserted into a vascular site such as an aneurysm to create an embolism therein; (b) a method of making the expansible implant; and (c) a method and an apparatus for embolizing a vascular site using the implant.
The embolization of blood vessels is desired in a number of clinical situations. For example, vascular embolization has been used to control vascular bleeding, to occlude the blood supply to tumors, and to occlude vascular aneurysms, particularly intracranial aneurysms. In recent years, vascular embolization for the treatment of aneurysms has received much attention. Several different treatment modalities have been employed in the prior art. U.S. Pat. No. 4,819,637xe2x80x94Dormandy, Jr. et al., for example, describes a vascular embolization system that employs a detachable balloon delivered to the aneurysm site by an intravascular catheter. The balloon is carried into the aneurysm at the tip of the catheter, and it is inflated inside the aneurysm with a solidifying fluid (typically a polymerizable resin or gel) to occlude the aneurysm. The balloon is then detached from the catheter by gentle traction on the catheter. While the balloon-type embolization device can provide an effective occlusion of many types of aneurysms, it is difficult to retrieve or move after the solidifying fluid sets, and it is difficult to visualize unless it is filled with a contrast material. Furthermore, there are risks of balloon rupture during inflation and of premature detachment of the balloon from the catheter.
Another approach is the direct injection of a liquid polymer embolic agent into the vascular site to be occluded. One type of liquid polymer used in the direct injection technique is a rapidly polymerizing liquid, such as a cyanoacrylate resin, particularly isobutyl cyanoacrylate, that is delivered to the target site as a liquid, and then is polymerized in situ. Alternatively, a liquid polymer that is precipitated at the target site from a carrier solution has been used. An example of this type of embolic agent is a cellulose acetate polymer mixed with bismuth trioxide and dissolved in dimethyl sulfoxide (DMSO). Another type is ethylene glycol copolymer dissolved in DMSO. On contact with blood, the DMSO diffuses out, and the polymer precipitates out and rapidly hardens into an embolic mass that conforms to the shape of the aneurysm. Other examples of materials used in this xe2x80x9cdirect injectionxe2x80x9d method are disclosed in the following U.S. Patents: U.S. Pat. No. 4,551,132xe2x80x94Pxc3xa1sztor et al.; U.S. Pat. No. 4,795,741xe2x80x94Leshchiner et al.; U.S. Pat. No. 5,525,334xe2x80x94Ito et al.; and U.S. Pat. No. 5,580,568xe2x80x94Greff et al.
The direct injection of liquid polymer embolic agents has proven difficult in practice. For example, migration of the polymeric material from the aneurysm and into the adjacent blood vessel has presented a problem. In addition, visualization of the embolization material requires that a contrasting agent be mixed with it, and selecting embolization materials and contrasting agents that are mutually compatible may result in performance compromises that are less than optimal. Furthermore, precise control of the deployment of the polymeric embolization material is difficult, leading to the risk of improper placement and/or premature solidification of the material. Moreover, once the embolization material is deployed and solidified, it is difficult to move or retrieve.
Another approach that has shown promise is the use of thrombogenic microcoils. These microcoils may be made of a biocompatible metal alloy (typically platinum and tungsten) or a suitable polymer. If made of metal, the coil may be provided with Dacron fibers to increase thrombogenicity. The coil is deployed through a micro catheter to the vascular site. Examples of microcoils are disclosed in the following U.S. patents: U.S. Pat. No. 4,994,069xe2x80x94Ritchart et al.; U.S. Pat. No. 5,133,731xe2x80x94Butler et al.; U.S. Pat. No. 5,226,911xe2x80x94Chee et al.; U.S. Pat. No. 5,312,415xe2x80x94Palermo; U.S. Pat. No. 5,382,259xe2x80x94Phelps et al.; U.S. Pat. No. 5,382,260xe2x80x94Dormandy, Jr. et al.; U.S. Pat. No. 5,476,472xe2x80x94Dormandy, Jr. et al.; U.S. Pat. No. 5,578,074xe2x80x94Mirigian; U.S. Pat. No. 5,582,619xe2x80x94Ken; U.S. Pat. No. 5,624,461xe2x80x94Mariant; U.S. Pat. No. 5,645,558xe2x80x94Horton; U.S. Pat. No. 5,658,308xe2x80x94Snyder; and U.S. Pat. No. 5,718,711xe2x80x94Berenstein et al.
The microcoil approach has met with some success in treating small aneurysms with narrow necks, but the coil must be tightly packed into the aneurysm to avoid shifting that can lead to recanalization. Microcoils have been less successful in the treatment of larger aneurysms, especially those with relatively wide necks. A disadvantage of microcoils is that they are not easily retrievable; if a coil migrates out of the aneurysm, a second procedure to retrieve it and move it back into place is necessary. Furthermore, complete packing of an aneurysm using microcoils can be difficult to achieve in practice.
A specific type of microcoil that has achieved a measure of success is the Guglielmi Detachable Coil (xe2x80x9cGDCxe2x80x9d). The GDC employs a platinum wire coil fixed to a stainless steel guidewire by a solder connection. After the coil is placed inside an aneurysm, an electrical current is applied to the guidewire, which heats sufficiently to melt the solder junction, thereby detaching the coil from the guidewire. The application of the current also creates a positive electrical charge on the coil, which attracts negatively-charged blood cells, platelets, and fibrinogen, thereby increasing the thrombogenicity of the coil. Several coils of different diameters and lengths can be packed into an aneurysm until the aneurysm is completely filled. The coils thus create and hold a thrombus within the aneurysm, inhibiting its displacement and its fragmentation.
The advantages of the GDC procedure are the ability to withdraw and relocate the coil if it migrates from its desired location, and the enhanced ability to promote the formation of a stable thrombus within the aneurysm. Nevertheless, as in conventional microcoil techniques, the successful use of the GDC procedure has been substantially limited to small aneurysms with narrow necks.
Still another approach to the embolization of an abnormal vascular site is the injection into the site of a biocompatible hydrogel, such as poly (2-hydroxyethyl methacrylate) (xe2x80x9cpHEMAxe2x80x9d or xe2x80x9cPHEMAxe2x80x9d); or a polyvinyl alcohol foam (xe2x80x9cPAFxe2x80x9d). See, e.g., Horxc3xa1k et al., xe2x80x9cHydrogels in Endovascular Embolization. II. Clinical Use of Spherical Particlesxe2x80x9d, Biomaterials, Vol. 7, pp. 467-470 (November, 1986); Rao et al., xe2x80x9cHydrolysed Microspheres from Cross-Linked Polymethyl Methacrylatexe2x80x9d, J. Neuroradiol., Vol. 18, pp. 61-69 (1991); Latchaw et al., xe2x80x9cPolyvinyl Foam Embolization of Vascular and Neoplastic Lesions of the Head, Neck, and Spinexe2x80x9d, Radiology, Vol. 131, pp. 669-679 (June, 1979). These materials are delivered as microparticles in a carrier fluid that is injected into the vascular site, a process that has proven difficult to control.
A further development has been the formulation of the hydrogel materials into a preformed implant or plug that is installed in the vascular site by means such as a micro catheter. See, e.g., U.S. Pat. No. 5,258,042xe2x80x94Mehta and U.S. Pat. No. 5,456,693xe2x80x94Conston et al. These types of plugs or implants are primarily designed for obstructing blood flow through a tubular vessel or the neck of an aneurysm, and they are not easily adapted for precise implantation within a sack-shaped vascular structure, such as an aneurysm, so as to fill substantially the entire volume of the structure.
There has thus been a long-felt, but as yet unsatisfied need for an aneurysm treatment device and method that can substantially fill aneurysms of a large range of sizes, configurations, and neck widths with a thrombogenic medium with a minimal risk of inadvertent aneurysm rupture or blood vessel wall damage. There has been a further need for such a method and device that also allow for the precise locational deployment of the medium, while also minimizing the potential for migration away from the target location. In addition, a method and device meeting these criteria should also be relatively easy to use in a clinical setting. Such ease of use, for example, should preferably include a provision for good visualization of the device during and after deployment in an aneurysm.
Broadly, a first aspect of the present invention is a device for occluding a vascular site, such as an aneurysm, comprising a conformal vascular implant, formed of an expansible material, that is compressible from an initial configuration for insertion into the vascular site by means such as a micro catheter while the implant is in a compressed configuration, and that is expansible in situ into an expanded configuration in which it substantially fills the vascular site, thereby to embolism the site, wherein the initial configuration of the implant is a scaled-down model of the vascular site.
In a preferred embodiment, the implant is made of a hydrophobic, macro porous, polymeric, hydrogel foam material, in particular a water-swellable foam matrix formed as a macro porous solid comprising a foam stabilizing agent and a polymer or copolymer of a free radical polymerizable hydrophobic olefin monomer cross-linked with up to about 10% by weight of a multiolefin-functional cross-linking agent. The material is modified, or contains additives, to make the implant visible by conventional imaging techniques.
Another aspect of the present invention is a method of manufacturing a vascular implant, comprising the steps of: (a) imaging a vascular site by scanning the vascular site to create a digitized scan data set; (b) using the scan data set to create a three-dimensional digitized virtual model of the vascular site; and (c) forming a vascular implant device in the form of a physical model of the vascular site, using the virtual model, the implant being formed of a compressible and expansible biocompatible foam material. In a specific embodiment, the forming step (c) comprises the substeps of: (c)(1) using the virtual model to create a scaled-down, three-dimensional physical mold of the vascular site; and (c)(2) using the mold to create a vascular implant in the form of a scaled-down physical model of the vascular site.
In the preferred embodiment of the method of manufacturing the implant, the imaging step is performed with a scanning technique such as computer tomography (commonly called xe2x80x9cCTxe2x80x9d or xe2x80x9cCATxe2x80x9d), magnetic resonance imaging (MRI), magnetic resonance angiography (MRA), or ultrasound. Commercially-available software, typically packaged with and employed by the scanning apparatus, reconstructs the scan data set created by the imaging into the three-dimensional digitized model of the vascular site. The digitized model is then translated, by commercially available software, into a form that is useable in a commercially available CAD/CAM program to create the scaled-down physical mold by means of stereolithography. A suitable implant material, preferably a macro porous hydrogel foam material, is injected in a liquid or semiliquid state into the mold. Once solidified, the hydrogel foam material is removed from the mold as an implant in the form of a scaled-down physical model of the vascular site.
A third aspect of the present invention is a method for embolizing a vascular site, comprising the steps of: (a) passing a micro catheter intravascularly so that its distal end is in a vascular site; (b) providing a vascular implant in the form of a scaled-down physical model of the vascular site, the implant being formed of a compressible and expansible biocompatible foam material; (c) compressing the implant into a compressed configuration dimensioned to pass through a micro catheter; (d) passing the implant, while it is in its compressed configuration, through the micro catheter so that the implant emerges from the distal end of the micro catheter into the vascular site; and (e) expanding the implant in situ substantially to fill the vascular site.
The apparatus employed in the embolization method comprises an elongate, flexible deployment element dimensioned to fit axially within an intravascular micro catheter; a filamentous implant retention element disposed axially through the deployment element from its proximal end to its distal end; and an implant device removably attached to the distal end of the retention element.
The implant device, in its preferred embodiment, is formed of a moldable, hydrophilically expansible, biocompatible foam material that has an initial configuration in the form of a scaled-down physical model of the vascular site, that is compressible into a compressed configuration that fits within the micro catheter, and that is hydrophilically expansible into an expanded configuration in which it is dimensioned substantially to conform to and fill the vascular site. Alternatively, the implant device may be formed of a non-hydrophobic foam material having an initial configuration that is substantially the same size and shape as the vascular site, and that restores itself to its initial configuration after it is released from its compressed configuration.
The retention element is preferably a flexible wire having a distal end configured to releasably engage the implant device while the implant device is in its compressed configuration, thus to retain the implant device within the distal end of the micro catheter while the distal end of the micro catheter is inserted into the vascular site. The wire is movable axially with the deployment element in the distal direction to expose the implant from the distal end of the micro catheter, and is movable proximally with respect to the deployment element to urge the implant device against the distal end of the deployment element, thereby push the implant device off of the wire. Thus released into the vascular site, the implant device expands into an expanded configuration in which it substantially conforms to and fills the vascular site.
The present invention provides a number of significant advantages. Specifically, the present invention provides an effective vascular embolization implant that can be deployed within a vascular site with excellent locational control, and with a lower risk of vascular rupture, tissue damage, or migration than with prior art implant devices. Furthermore, the implant device, by being modelled on the actual vascular site in which it is to be implanted, effects a conformal fit within the site that promotes effective embolization, and yet its ability to be delivered to the site in a highly compressed configuration facilitates precise and highly controllable deployment with a micro catheter. In addition, the method of fabricating the implant device, by modeling it on each individual site, allows implant devices to be made that can effectively embolism vascular sites having a wide variety of sizes, configurations, and (in the particular case of aneurysms) neck widths. These and other advantages will be readily appreciated from the detailed description that follows.

Vascular embolization with an expansible implant