Methods, systems, and computer program products that enable a travel agent to selectively share information related to a plurality of travel products with a traveler. In response to a search query from the travel agent, an information sharing module receives information relating to the plurality of travel products from a travel database system. The information sharing module causes the information to be displayed to a travel agent on a first display of a travel agency system. In response to the travel agent selecting a subset of the travel products, the information sharing module displays information relating to the subset of travel products to the traveler on a second display separate from the first display. The information sharing module may be configured to reformat the information so that the information is adapted to the traveler, and to cause travel products selected by the traveler to be booked.

The invention generally relates to computers and computer software and, in particular, to methods, systems, and computer program products for displaying travel information to, and interacting with, the traveler for booking travel products.
Travel agents typically access computer reservation systems or other travel product related systems to search for and plan travel itineraries for travelers. Computer reservation systems typically include one or more databases that store and retrieve information on travel product cost and availability. Computer reservation systems may also conduct transactions related to booking air, rail, shuttle, or bus travel, hotel rooms, rental cars, and other travel products. A system configured to book reservations for multiple travel product providers is commonly referred to as a Global Distribution System (GDS). A GDS is typically operated by a third party service provider. Third party service providers may offer GDS services that connect travel product provider systems to travel agency systems. The GDS may thereby enable travel agents to search for and sell travel products offered by multiple travel product providers.
During the process of selling travel products to a traveler in a face-to-face situation, the travel agent may request that the traveler decide on certain aspects of the itinerary. For example, the traveler may need to decide which flight, hotel, or other travel-related services they want to book for the trip. If the traveler is physically present in the travel agent's office, the travel agent will often point their display toward the traveler so that the traveler can directly view the travel information. However, the data displayed by a travel agency system is often cryptic in nature and not well adapted to interpretation by the traveler. For example, certain information may be provided using codes and industry specific language or jargon that is not understandable by the traveler. This information may be presented over a command line interface unsuited for viewing by travelers. Moreover, the travel agency system may also display confidential information, such as commissions, margins, or discounted prices that should not be disclosed to the traveler.
Thus, improved systems, methods, and computer program products for displaying information relating to travel products are needed that enable travelers to view and comprehend the information being displayed.


Various techniques associated with application performance monitoring are disclosed. In some embodiments, a subset of application methods is configured to capture response time metrics, and response time metrics for a prescribed application transaction are computed by summing corresponding response time metrics of methods of the subset that are executed during each transaction invocation. Method and transaction response time metrics are collected for each of a plurality of observation intervals, and the collected response time metrics are analyzed to identify anomalous method and transaction states. Co-occurring anomalous transaction and method states are correlated to identify a set of hotspot methods for the transaction, wherein hotspot methods comprise expected root causes for anomalies of the transaction.

Existing techniques for application performance monitoring comprise entire stack tracing, i.e., monitoring all invoked methods for performance issues. However, in a typical application comprising a large number of methods, monitoring application performance in such a brute force manner leads to system degradation to such an extent that the monitoring is not even possible in a production environment.


A medical system comprises a probe comprising a terminal distal end. The system further comprises a first coil in the probe and comprises a guide instrument including a terminal distal end and defining a lumen sized to guide the probe. The probe can be inserted through the lumen to reach a worksite. At the worksite, the terminal distal end of the probe is configured to reach at least the terminal distal end of the guide instrument. The system further comprises a sensor embedded in a wall of the guide instrument and comprises processing hardware configured to receive a first induced signal from the first coil and to receive from the sensor an indication of a pointing direction of the guide instrument. The processing hardware is configured to use the first induced signal and the indication of the pointing direction to determine a roll angle of the probe.

Minimally invasive medical devices that navigate natural body lumens need to be small enough to fit within the lumens. Lung catheters, for example, which may be used to perform minimally invasive lung biopsies or other medical procedures, may need to follow airways that decrease in size as the catheter navigates branching passages. To reach a target location in a lung, a catheter may follow passages having diameters as small as 3 mm or less. Manufacturing a catheter that is sufficiently small and includes the mechanical structures and sensors for remote or robotic operation can be challenging.
Electromagnetic sensors (EM) sensors can measure the position and orientation of a portion of a medical instrument. EM sensors are particularly suitable for minimally invasive medical instruments because EM sensors can combine high global accuracy with a small diameter package size. During EM sensor operation, a generator external to a patient can produce a well-controlled, time-varying magnetic field, and in response, one or more coils of an EM sensor in or on a portion of the medical instrument produce induced electrical signals. In particular, time variations in the magnetic field induce currents in the coils of the EM sensor, and the pose of each coil can be partially determined from knowledge of the generated magnetic field and the geometry of the coil. A single coil can be used, for example, to measure a position and a pointing direction, e.g., pitch and yaw angles, but a cylindrically symmetrical coil is unable to distinguish roll angles about the symmetry axis of the coil. Accordingly, EM sensors employing a single cylindrical coil have been used as 5-Degree-of-Freedom (5-DoF) sensors. To additionally measure the roll angle, a 6-DoF EM sensor generally requires two coils having symmetry axes that are not parallel, e.g., perpendicular symmetry axes.
The long, thin shape typical of 5-DoF EM sensors fits well with minimally invasive medical instruments or tools, which often have long and thin extensions. However, with the central axis of a single coil sensor aligned with the roll axis of an instrument, such 5-DoF EM sensors cannot measure the roll angle of the instrument. While some symmetric instruments such as needles may not require roll angle measurements, many instruments require knowledge of the roll angle of the instrument, particularly for robotic control. Measurement of the roll angle may require a 6-DoF sensor that includes two coils. For example, to create a 6-DoF EM sensor, two 5-DoF EM sensors may need to be placed perpendicular or at a non-zero angle to each other, which creates a much larger sensor package. If each 5-DoF sensor has a cylindrical shape about 1 mm in diameter and about 10 mm long, the 6-Dof sensor containing two 5-DoF sensors may be up to 10×10×1 mm. While the 1 mm diameter of a 5-DoF EM sensor may fit within a small, e.g., 3 mm diameter, instrument, a 10-mm wide 6-DoF EM sensor may not fit in a small instrument.

Electromagnetic sensor with probe and guide sensing elements


A liquid crystal display (LCD) panel is disclosed. The LCD panel includes a plurality of pixels arranged in rows and columns, a first sub gate-line coupled to first row-pixels that are adjacent to a lower side of the first sub gate-line, a second sub gate-line coupled to second row-pixels that are adjacent to an upper side of the second sub gate-line, a plurality of gate-lines between the first sub gate-line and the second sub gate-line, a plurality of even data-lines coupled to first column-pixels that are adjacent to the even data-lines, and a plurality of odd data-lines coupled to second column-pixels that are adjacent to the odd data-lines. Here, each gate-line of the plurality of gate lines is coupled to first row-pixels that are adjacent to a lower side of the gate-line and second row-pixels that are adjacent to an upper side of the gate-line.

1. Field
Aspects of embodiments according to the present invention relate to a display device. More particularly, aspects of embodiments according to the present invention relate to a liquid crystal display (LCD) panel, an LCD device, and a method of driving an LCD device.
2. Description of Related Art
A liquid crystal display (LCD) device displays an image by forming an electric field (i.e., an electric potential difference) between a pixel electrode and a common electrode of a liquid crystal capacitor included in each pixel. In the liquid crystal capacitor, a liquid crystal layer is placed between the pixel electrode and the common electrode so that light transmittance of the liquid crystal layer is controlled by an intensity of the electric field formed between the pixel electrode and the common electrode. Recently, an LCD device having a thin film transistor (TFT) as a switching element included in each pixel has been in widespread use. This type of LCD device has been referred to as a TFT LCD device.
An LCD device may periodically invert polarities of data signals to reduce or prevent deterioration of the liquid crystal capacitor included in each pixel due to polarization. For example, the LCD device may employ inversion methods such as a dot inversion method, a line inversion method, a column inversion method, a frame inversion method, a Z-inversion method, an active level shift (ALS) inversion method, etc. However, these inversion methods may cause various problems, such as horizontal crosstalk, vertical crosstalk, unnecessary power consumption, etc.

Liquid crystal display panel, liquid crystal display device, and method of driving a liquid crystal display device


A battery having a filling part and a pair of tab terminals on a convex portion of an upper surface of a cover so as to enable a connecting operation by mounting a receptacle housing of faston terminal type, and a manufacturing method for the cover for use in the battery. [1] A battery, in which projecting ends of the pair of tab terminals are located with the filling part positioned between them and are projected in the same side in a longitudinal direction so that the projecting ends are positioned on an upper surface of the cover. [2] A battery, in which two concave portions are formed on side surfaces other than those to which the receptacle housing of convex portion are mounted, the two concave portions opening only on side surfaces of the convex portion extending downward from positions displaced from the upper surface of the convex portion, or opening over areas ranging from the side surfaces of convex portion to the side surfaces of cover, and charge terminals are installed in the concave portions adjacent to their upper surfaces.

This invention relates to a battery having a filling part and a pair of tab terminals on a convex portion of an upper surface of a cover so as to enable a connecting operation by mounting a receptacle housing of faston terminal type, and further to a manufacturing method for the cover for use in the battery.
Generally, batteries for use in small motorcycles and domestic electric equipments are made into very compact sizes. A battery having a filling part and terminals on an upper surface of cover, as described in Unexamined Patent Publication No. 2-129849 for example, is well known as a battery of such type. In this battery, a terminal wall, in parallel with filling parts arranged in longitudinal direction, is formed, and terminals are installed on a side surface of the terminal wall.
In the above structure, however, it is required to connect a coupler to each terminal. It is difficult to position the coupler so that connecting the coupler is easy.
On the other hand, a charge operation is generally carried out by holding a charge clip to a terminal of cover in the battery. It is hard to hold the charge clip and the terminal can be damaged by operation mistake.
Further, a method using plural molds as illustrated by FIG. 16, is well known a for manufacturing the cover by embedding a part of a terminal shown in FIG. 15 in the cover of battery. In this method, a terminal 9 is supported at its portions 90 and 92 by a movable mold B and a stationary mold D, and is disposed in a space 70 formed by an upper mold A, movable mold B, a vertically movable mold C and a stationary mold D. Synthetic resin, such as polypropylene etc. is filled in space 70 from a resin filling port 71 in the upper mold A.
In the above-mentioned method, however, filling pressure of synthetic resin, during molding, becomes extremely large, as high as 700 to 1,400 kg/cm.sup.2. Consequently, longitudinal portion 91 of terminal 9 deformed to become in contact with an upper part of the stationary mold D and exposed after completion of the cover. Thus it is necessary to resort to other methods in order to prevent the possibility that the exposed portion 91 will come into contact with an electrolyte.
This invention is concerned with solving the above problem encountered in prior arts. A first object of the invention is to provide a battery having a simple positioning of the receptacle housing and allowing an easy connection of the receptacle housing, when connecting the receptacle housing of the faston terminal type to a tab terminal installed on the cover.
A second object of the invention is to provide a battery enabling a charge operation by easily connecting a standard charge clip.
A third object of the invention is to provide a manufacturing method for a battery cover preventing the terminal from being exposed and come into contact with an electrolyte.

Battery and manufacturing method for battery cover

c/o Yuasa Battery Co., Ltd., 6-6, Josai-cho

c/o Kabushiki Kaisha Honda Gijutu Kenkyusho 4-1, Chuo 1-chome


The present disclosure relates to a closure for a reclosable package wherein the product side flanges include opposing air pockets thereby allowing a user to more easily grab the product side flanges or the package walls. In a second embodiment of the disclosure, the opposing air pockets are adjacent to the interlocking elements of the closure. In a further aspect of the disclosure, a closure includes a small sack or air or other fluid adjacent to the closure profiles. When closed, the closure creates a leak resistant configuration. By pressing the air sack, the user separates the closure profiles.

Field of the Disclosure
The present disclosure relates to a closure for a reclosable package wherein air pockets are formed on the flanges of the closure. A further aspect of the present disclosure relates to a closure which contains a small sack of air adjacent to and impinging upon the closure profiles. When closed, the closure creates a leak-resistant configuration. By pressing the air sack, the user separates the closure profiles.
Description of the Prior Art
Closures for reclosable packages are well-known in the prior art and well-developed for their intended purposes. However, sometimes it may be difficult for the consumer, particularly if aged or otherwise challenged, to grab the flanges or package walls in order to separate the flanges or package walls thereby opening the package.
Moreover, in the marketplace, there may be a movement away from rigid packaging to flexible packaging, with an interest in "liquid pouches". While spouts are frequently provided for such packages, the traditional way of opening a zipper or closure can be inconvenient in that this requires two hands instead of one.

Air pocket flange closure for push-to-open recloseable packages


A capping structure is provided for a spin valve sensor which improves its magnetoresistive coefficient (dr/R). In one embodiment the capping structure includes a first layer of cobalt iron (CoFe) and a second layer of tantalum (Ta). In a second embodiment the capping structure includes a first layer of cobalt iron (CoFe) or cobalt (Co), a second layer of copper (Cu) and a third layer of tantalum (Ta).

1. Field of the Invention
The present invention relates to a spin valve with an improved capping layer structure and, more particularly, to a capping layer structure for a spin valve that improves a magnetoresistive coefficient and thermal stability.
2. Description of Related Art
An exemplary high performance read head employs a spin valve sensor for sensing magnetic fields on a moving magnetic medium, such as a rotating magnetic disk or a linearly moving magnetic tape. The sensor includes a nonmagnetic electrically conductive first spacer layer sandwiched between a ferromagnetic pinned layer and a ferromagnetic free layer. An antiferromagnetic pinning layer interfaces the pinned layer for pinning the magnetic moment of the pinned layer 90.degree. to an air bearing surface (ABS) which is an exposed surface of the sensor that faces the magnetic medium. First and second leads are connected to the spin valve sensor for conducting a sense current therethrough. The magnetic moment of the free layer is free to rotate in positive and negative directions from a quiescent or zero bias point position in response to positive and negative magnetic signal fields from a moving magnetic medium. The quiescent position is the position of the magnetic moment of the free layer when the sense current is conducted through the sensor without magnetic field signals from a rotating magnetic disk. The quiescent position of the magnetic moment of the free layer is preferably parallel to the ABS. If the quiescent position of the magnetic moment is not parallel to the ABS the positive and negative responses of the free layer will not be equal which results in read signal asymmetry.
The thickness of the spacer layer is chosen so that shunting of the sense current and a magnetic coupling between the free and pinned layers are minimized. This thickness is less than the mean free path of electrons conducted through the sensor. With this arrangement, a portion of the conduction electrons is scattered by the interfaces or boundaries of the spacer layer with the pinned and free layers. When the magnetic moments of the pinned and free layers are parallel with respect to one another scattering is minimal and when their magnetic moments are antiparallel scattering is maximized. An increase in scattering of conduction electrons increases the resistance of the spin valve sensor and a decrease in scattering of the conduction electrons decreases the resistance of the spin valve sensor. Changes in resistance of the spin valve sensor is a function of cos .theta., where .theta. is the angle between the magnetic moments of the pinned and free layers. This resistance, which changes when there are changes in scattering of conduction electrons, is referred to in the art as magnetoresistance (MR). Magnetoresistive coefficient is dr/R where dr is the change in magnetoresistance of the spin valve sensor from minimum magnetoresistance (magnetic moments of free and pinned layers parallel) and R is the resistance of the spin valve sensor at minimum magnetoresistance. For this reason a spin valve sensor sometimes referred to as a giant magnetoresistive (GMR) sensor. A spin valve sensor has a significantly higher magnetoresistive (MR) coefficient than an anisotropic magnetoresistive (AMR) sensor.
The spin valve sensor is located between first and second nonmagnetic nonconductive first and second read gap layers and the first and second read gap layers are located between ferromagnetic first and second shield layers. The distance between the first and second shield layers is referred to in the art as the read gap. The read gap determines the linear bit density of the read head. When a magnetic disk of a magnetic disk drive rotates adjacent the read sensor, the read sensor detects magnetic field signals from the magnetic disk only within the read gap, namely the distance between the first and second shield layers.
Efforts continue to increase the magnetoresistive coefficient (dr/R) of spin valve read heads. An increase in the magnetoresistive coefficient (dr/R) equates to higher bit density (bits/square inch of the rotating magnetic disk) read by the read head. One way to increase the magnetoresistive coefficient (dr/R) is to improve the performance of the various layers of the spin valve sensor. For instance, it is important that the ferromagnetic layers of the spin valve sensor have a uniform texture so as to promote stability of the magnetization of the layer. Further, the compositions of adjacent layers are important. When a first layer is formed on a second layer the characteristics of the first layer are somewhat dependent upon the characteristics of the second layer. This may be due to the grain structure of the second layer being affected by the grain structure of the first layer or a partial diffusion of the layers at the interface.
It should be understood that the performance of the spin valve sensor can be affected by subsequent processing steps, such as setting the magnetization of the hard bias layers, formation of the second shield layer and hard baking of photoresist layers to form the insulation stack of the write head. A temperature of 230.degree. C.-250.degree. C. for a period of 10 hours is typically employed for hard baking the photoresist layers of the insulation stack. This hard baking is done in the presence of a field which is perpendicular to the ABS so as not to disturb the orientation of the magnetic spins of the antiferromagnetic pinning layer of the spin valve sensor. However, the high temperature annealing typically causes a reduction in the magnetoresistive coefficient (dr/R) of the spin valve sensor due to a change in the texture of the layers or interfacial interaction between adjacent layers.

Spin valve with improved capping layer structure

International Business Machines Corporation


A gasification melting facility comprises: a fluidized bed gasification furnace that generates pyrolysis gas by thermally decomposing waste and discharges incombustibles; a melting furnace into which the pyrolysis gas is fed; a pyrolysis gas passage that connects the fluidized bed gasification furnace and the melting furnace; a grinder that grinds the incombustibles discharged from the fluidized bed gasification furnace by passing the incombustibles through a plurality of rods; a vibratory sifter that screens the incombustibles ground in the grinder; a fixed amount feeder that feeds at a fixed amount the incombustibles that pass through the vibratory sifter, the fixed amount feeder including a plurality of transfer chambers rotatable between a position to receive the incombustibles from the vibratory sifter and a position to discharge the incombustibles; and an airflow conveyor that conveys the fixed amount of the incombustibles from the fixed amount feeder together with airflow.

Gasification and melting system technology with wide application to the treatment of waste such as municipal waste and also incombustible waste, burned residue, and sludge is known. Such gasification and melting systems are provided with: a gasification furnace that gasifies waste by thermally decomposing the waste; a melting furnace that combusts pyrolysis gas generated by the gasification furnace at high temperatures and converts ash contained in the gas into molten slag, the melting furnace being disposed downstream of the gasification furnace; and a secondary combustion chamber that combusts flue gas discharged from the melting furnace. To achieve the recycling, volume reduction, and detoxification of waste, gasification and melting systems allow the slag extracted from the melting furnace to be used for construction material such as road bed material. Gasification and melting systems recover waste heat from the flue gas discharged from the secondary combustion chamber to generate electricity.
A fluidized bed gasification furnace is widely used as the gasification furnace of such a gasification and melting system. At the bottom of such a fluidized bed gasification furnace is formed a fluidized bed that is a fluid medium being fluidized by the supply of combustion air. Fluidized bed gasification furnaces are devices that partially combust the waste fed to the fluidized bed and thermally decompose the waste in the fluidized bed maintained at high temperatures by combustion heat.
Additionally, fluidized bed gasification furnaces are configured to discharge sand, which is the fluid medium, and incombustibles from the bottom of the furnace. A need exists for such a gasification melting facility to be capable of volume reduction. The reduction of incombustibles, which ultimately end up as landfill, is a matter of importance. Known means of reducing the volume of incombustibles that ultimately end up as landfill include methods of recovering valuable metals such as iron and aluminum contained in the incombustibles.
Another example of means of reducing the volume of waste is a gasification melting facility described in Patent Document 1, in which the fluid medium is separated from residues at the bottom of the fluidized bed gasification furnace, and the fluid medium is recovered to be reused. The metals contained in the residues at the bottom are sorted and collected. The non-metals are reused after pollutants are removed from the surface via abrasion. Patent Document 1 also describes technology of conveying pulverized non-metals to the melting furnace via airflow.

MITSUBISHI HEAVY INDUSTRIES ENVIRONMENTAL & CHEMICAL ENGINEERING CO., LTD.


This invention is directed to continuous, non-maligant, neuronal cell lines, the cells of which: a) in the undifferentiated form are essentially free of branched process; b) stain positively for neurofilament protein and neurotransmitters; c) do not stain positively for glial fibrillary acidic protein; and d) in the presence of nerve growth factor differentiate into cells with long branched processes. Derivative cell lines of such cell lines are also contemplated. The cell lines are useful in screening methods for evaluation of chemical and biological compounds as well as for therapeutic uses.

The failure of neurons in the central nervous system to regenerate is responsible for much of the disability associated with clinical damage to the central nervous system (CNS). Additionally, because CNS neurons do not regenerate, it has not been possible to develop continuous human cultures of such neurons.
The great heterogeneity of the central nervous system (CNS) has precluded extensive molecular characterization of CNS neurons. Techniques previously utilized to establish cell lines have significant limitations. Primary cultures are heterogeneous and have limited life-spans, whereas cell lines derived from malignant tumors and somatic cell hybrids may differ from the mature neuronal phenotype.
Many of the major advances in biomedical research stem from the use of continuous culture of cells from many parts of the body. There is a need for continuous human cortical neuronal cell lines to permit characterization of CNS neurons. Such a continuous cell line would also permit the screening of compounds to determine their effect on neural cells.


A method of operating a semiconductor memory device includes checking an erase-program cycling number, setting a target erase level to be maintained when the erase-program cycling number is less than a predetermined critical number, and setting the target erase level to be increased when the erase-program cycling number is greater than or equal to the predetermined critical number, and performing an erase operation so that threshold voltages of selected memory cells are less than the set target erase level.

1. Field of Invention
Various embodiments of the present invention relate to a semiconductor design technology and, more particularly, to an erase operation of a semiconductor device.
2. Description of Related Art
A semiconductor memory device, for example, a NAND flash memory, includes a memory cell array in which data are stored. The memory cell array includes a plurality of cell blocks. When program, erase and read operations are performed, a cell block may be selected from among the plurality of cell blocks included in the memory cell array, and corresponding operations may be performed on the selected cell block.
During an erase operation, 0V may be applied to word lines coupled to memory cells within a selected cell block, or the word lines may be floated while an erase voltage may be applied to a bulk of the selected cell block. The bulk is a region where a well within a substrate including the cell blocks is formed.
Recently, an erase operation is performed using an incremental step pulse erase (ISPE) method to reduce width of threshold voltage distributions of memory cells being erased. An erase operation using the ISPE method may be performed by repeating a plurality of erase loops.
An erase loop may include an operation of reducing threshold voltages of memory cells by applying an erase voltage to a bulk and an erase verify operation being carried out as to whether or not the threshold voltages of the memory cells in a selected cell block are reduced to a target level. During the erase verify operation, the target level may be determined depending on an erase verify voltage being applied to all of word lines coupled to the selected cell block. In general, in terms of the erase verify voltage, a voltage having a fixed level may be used.
As a result of the erase verify operation, if it is determined that there are memory cells having threshold voltages not reduced to the target level, the erase loop may be repeated until the threshold voltages of all the memory cells in the selected cell block are reduced to the target level while the erase voltage being applied to the bulk is gradually increased. The erase operation is completed when the threshold voltages of all of the memory cells in the selected cell block are reduced to the target level.
However, as an erase-program cycling number increases, the semiconductor memory device may be physically degraded due to physical properties thereof, and electrical characteristics of the semiconductor memory device may also be degraded. The erase-program cycling number refers to how many times a pair of a program operation and an erase operation is performed. In other words, a single set of program and erase operations may refer to a single erase-program cycling. As the erase-program cycling number increases, erase disturbance of memory cells may be more likely to occur. As a result, it may be more difficult to reduce threshold voltages of the memory cells to a target erase level during an erase operation, and an erase voltage with a higher voltage level may be required to reduce the threshold voltages of the memory cells to the target erase level. In addition, as the time taken to reduce the threshold voltages to the target erase level increases, stress on the semiconductor memory device may also increase.

Semiconductor memory device and method of operating the same


A fluid transport conduit for conveying ink-jet ink from a reservoir to a printhead in an ink-jet printer is provided. The fluid transport conduit comprises at least one inner layer, such as high density polyethylene, cyclic olefin copolymer, or polypropylene homopolymer, that is flexible and is a barrier to liquids, and at least one outer layer, such as nylon or polyvinyl alcohol, that is a barrier to air and is softer, or more compliant, than the inner layer, with the inner layer bonded to the outer layer. The two layers are advantageously co-extruded to form the fluid transport conduit.

The present invention is directed to ink-jet printers and, more particularly, to ink-jet printers employing an off-axis ink delivery system for replenishing on-axis print cartridges with ink.
In a conventional ink jet printer, ink is deposited on record media such as paper via a disposable pen, the pen being mounted on a carriage for reciprocation across the paper""s face. Ink is ejected through the pen""s printhead, the printhead being connected to a volume of ink which is stored in a reservoir onboard the pen. When the ink reservoir is depleted, the pen is removed from the carriage, discarded, and replaced with a new pen. An example of such a pen is disclosed in U.S. Pat. No. 4,771,295, which is entitled xe2x80x9cThermal Ink Jet Pen Body Construction Having Improved Ink Storage and Feed Capabilityxe2x80x9d, and which is commonly owned herewith. The disclosure of that patent is incorporated herein by this reference.
In order to extend the useful life of ink jet pens, several off-axis ink supply approaches have been suggested whereby the pen""s onboard ink reservoir is refilled. These approaches have included the use of a second, off-board ink supply, generally in the form of a larger ink reservoir positioned at a location which is remote from the pen. As the pen""s onboard supply of ink is depleted, substitute ink is delivered from the off-board reservoir through an arrangement of one or more tubes. The larger ink reservoir thus allows for use of the pen beyond the duration of the its onboard ink supply, effectively extending the pen""s lifetime to coincide with the lifetime of the its associated printhead. An illustrative example of such an approach is provided in U.S. Pat. No. 4,831,389, which is entitled xe2x80x9cOff Board Ink Supply System and Process for Operating an Ink Jet Printerxe2x80x9d, and which is commonly owned herewith. The disclosure of that patent is incorporated herein by this reference.
Although known off-axis ink supply approaches generally have been effective in extending the lifetime of a printer""s pen, there remains room for improvement, particularly in the manner by which ink is delivered to the pen. In the past, ink has been delivered via flexible tubing which runs from the off-board ink supply to the reservoir within the pen. The tubing generally extends as a linear segment, each tube having a length which allows for reciprocation of the pen. As the pen reciprocates, and the distance between the pen and off-board reservoir changes, the tubing is bent over on itself so as to take up the resulting slack.
This tubing arrangement has led to a number of problems, due in large part, to the effects of tube bending during reciprocation of the pen. Such bending, for example, will often produce an unacceptably high stress on the tube, increasing tube fatigue, and correspondingly decreasing the lifetime of the tube. In addition, bending of the tubes may result in an undesirably high torque on the pen carriage, increasing the power required to drive the pen. Further, because the bending of tubes requires a significant amount of clearance, the use of off-axis ink supplies has resulted in a significant increase in the printer""s size. The latter problem is particularly troublesome where a multi-color pen is employed, it being necessary to run a plurality of tubes (one for each color) between the reservoir and the reciprocating pen.
In spite of the foregoing, other solutions, such as the use of a rigid tube, as disclosed, for example, in commonly-owned U.S. Pat. No. 5,691,754, entitled xe2x80x9cRigid Tube Off-Axis Ink Supplyxe2x80x9d, do not offer the potential advantages provided by flexible tubing, or conduit. Specifically, flexible conduit permits more facile movement of the print heads.
In addition to the foregoing, the conduit must also contain and deliver ink under various environmental conditions and usages. The conduit must balance the following requirements:
the conduit must be sized large enough to deliver the required amount of ink flow;
stiffness must not affect carriage dynamics, or pen seating;
bend diameters must be kept to a minimum for product size/layout;
the conduit must withstand five years of carriage cycles;
the conduit must maintain properties over shipping and operating temperatures;
the conduit must be able to withstand chemical attack from inks or other outside contaminants;
the conduit must be able to contain ink without letting air diffuse in or water vapor diffuse out;
the conduit must be able to bend in small arcs for routing in the product without kinking; and
the conduit must be consistently processable and cost effective.
Defining a material is challenging because several of these requirements pull material properties in opposite directions. Work on tubing solutions has been on-going for the past several years and has resulted in a number of solutions, but none have been totally satisfactory to date. The technologies and materials that have been available are limited and the products have had to make large sacrifices. One printer product was released with a Teflon-based material (polychlorotrifluoroethylene; PCTFE), which had fatigue issues, and then was changed to another Teflon-type material (fluorinated ethylene propylene; FEP), which had processing and diffusion issues. Another printer product started with Saran, which is polyvinylidene dichloride, which had processing and fatigue issues, and then was changed to low density polyethylene, which was a compromise to diffusion. The available options for materials that adequately satisfy the above-listed design requirements have, for the most part, been exhausted.
Thus, there remains a need for a fluid transport conduit that allows design freedom while using the existing material base and is impermeable to air and ink while retaining bending flexibility.
In accordance with the present invention, a fluid transport conduit for conveying ink-jet ink from a reservoir to a printhead is provided. The fluid transport conduit comprises an inner layer that is flexible and comprises a barrier to liquid and an outer layer that is a barrier to air and is more compliant than the inner layer, with the inner layer bonded to the outer layer.
Depending on the materials used for the inner layer and the outer layer, an adhesive may be used to bond the two layers together. Alternatively, the inner and outer layers may be bonded together naturally by a co-extrusion process. Further, either or both of the inner layer and outer layer may include more than one material for further tailoring the properties of the conduit.
Employing an inner layer that is flexible and is a barrier to liquid and an outer layer that is more compliant than the inner layer and is a barrier to air results in a fluid transport conduit that is flexible during movement of the printhead, yet protects the ink from the effects of air, while preventing leakage of ink into the printer.

Co-extruded tubing for an off-axis ink delivery system

Hewlett-Packard Development Company, L.P.


A stator coil of a slotless motor is disclosed in which the stator coil is formed in such a manner that respective both distal ends of two unit coil bodies, each unit coil body arranged to face each other, are respectively coupled to form a plurality of circular coil bodies, each circular coil body having a different inner diameter, and a circular coil body having a smaller inner diameter is sequentially inserted into an inner side of a circular coil body having a larger inner diameter, whereby a horizontal width of the plurality of unit coil bodies of U, V and W phases is equal there among to cause the strength of the magnetic field of U, V and W phases to be equal, and to allow the stator to be accurately manufactured, thereby catering to a designer's intention and markedly simplifying the assembly processes.

1. Field of the Invention
The present invention relates generally to electrical machines, and more particularly to a slotless motor.
2. Description of the Background
Typically, a motor is composed of a stator and a rotor. The stator is arranged at an inner side of a core formed with a plurality of slots, and stator coils are wound in the slots with insulated conductors. The rotor is arranged on a rotating axis with a permanent magnet, and is rotationally installed inside of the stator.
In a case a current is applied to a stator coil of the motor, a magnetic field is generated from the stator coil, and the rotor is rotated by inter-action of the magnetic field formed by the stator coil and the magnetic field generated by the permanent magnet of the rotor.
The stator, as mentioned above, is mounted with slots, each spaced at a predetermined distance, inside of the core, and the slot is arranged with a stator coil wound with insulated conductors. However, the core arranged with the slots there inside has a drawback in that it increases the manufacturing cost, and decreases the output efficiency of motor due to the difficulty in winding the insulated conductors thereon.
As a result, a slotless motor has been developed in which no slots are formed inside the core, insulated conductors are wound to form a plurality of units comprising a coil body (hereinafter referred to as unit coil body), and a stator coil comprising the plurality of unit coil bodies is arranged inside the core.
The slotless motor is structurally simple and is capable of reducing the manufacturing cost since no slots are arranged inside the core. Furthermore, the slotless motor has an advantage in that it is arranged with a plurality of unit coil bodies in a uniform high density such that vibration and noise caused by torque ripple are reduced and motor output efficiency is very high.
In manufacturing the stator coil of the conventional slotless motor, the insulating conductor windings are formed in a predetermined shape, such as a rectangular or trapezoid shape, to form a unit coil body, and a plurality of unit coil bodies are alternatively circumferentially arranged to allow one side of the unit coil body to be positioned back and forth. Furthermore, each of the plurality of unit coil bodies is arranged with an offset to allow both sides of a unit coil body to be positioned up and down.
However, the conventional slotless motor suffers from drawbacks in that accurate offset designing and manufacturing processes are required for a precise arrangement of the plurality of unit coil bodies, and a relative distance error between the plurality of unit coil bodies is generated to decrease an output characteristic of the motor in the course of continuously arranging the plurality of unit coil bodies.


An eye proptosing speculum that applies pressure to urge the eyeball outwardly is disclosed. The speculum includes a pair of blades and a pair of pressors. The pair of blades are opposingly situated and extend generally posteriorly. Each blade is shaped to engage the patient between one of the eyelids and the eyeball. The pair of pressors are also opposingly situated and extend generally posteriorly. One pressor extends from each blade and each pressor is shaped to engage and to exert pressure on the peripheral orbital contents. The pressure is transferred to the posterior orbital contents and then to a posterior region of the eyeball to proptose the eyeball outwardly. Each blade and each pressor, in combination, generally extend to follow the exterior surface of the eyeball, and each blade and each pressor is shaped to minimize extrinsic pressure directly on the eyeball. The eye proptosing speculum has a pair of arms attached to and cooperating with each other, with one blade being attached to each of the arms. Preferably, the speculum has an adjustment device for adjustably fixing the distance between the free ends of the arms.

When performing eye surgery, it may be necessary to hold back the upper and lower eyelids by way of an eye speculum. Such an eye speculum may comprise a two-armed instrument with an adjusting device for finely adjusting the angle of one arm with respect to the other. Additionally, such an eye speculum has a retractor or blade at the distal end of each arm that may comprise a scoop-shaped piece in cross-section. Each scoop is inscribed around and under a respective eyelid, and the eye speculum holds the eyelids back when the adjusting device is adjusted to open the angle between the arms. Normally, an eye speculum is designed and employed such that pressure is not exerted on the eyeball since pressure tends to distort the eyeball. Moreover, excessive pressure may cause protrusion of the ocular contents and thereby complicate intraocular surgery.
When performing certain surgical procedures on the eye which do not involve opening the eyeball, it is preferable to proprose the eyeball outwardly to expose more of the surface of and allow greater access to the eyeball. An example of such a surgical procedure is an automated lamellar keratectomy (ALK), where a relatively large vacuum fixation ring is applied to the front surface of the eyeball. As may be understood, the application of the ring is more easily performed when greater exposure of the front surface of the eyeball is provided.
Accordingly, it would be advantageous to provide a surgical instrument that safely and easily proproses the eyeball outwardly to allow greater access to the exposed surface of the eyeball during eye surgery.


Provided are an apparatus and a method for controlling an image in a mobile communication terminal. The apparatus includes a display for displaying an enlarged image; and a controller for, when an input for enlarging an image is detected, enlarging the image in a position in which the input for enlarging the image is detected, and displaying the enlarged image on the display. The apparatus controls the size of the image displayed on the display of the mobile communication terminal, allowing convenient access to data displayed on the display and the selection of menus on the enlarged image and convenience in selecting menus from a small display.

1. Field of the Invention
The present invention relates generally to an apparatus and method for controlling displaying of an image in a mobile communication terminal, and in particular, to an apparatus and method for controlling the enlarging/reducing and moving of a displayed image in a mobile communication terminal.
2. Description of the Related Art
Mobile communication terminals are indispensable items for modern consumers, regardless of gender and age, and demand for them is expected to increase. Consequently, service providers and terminal manufacturers are competitively developing new products and services to attract potential users.
For example, mobile communication terminals have phone directories, games, short message, e-mail, wake-up call alarm, Moving Pictures Experts Group (MPEG) Layer 3 (MP3), digital camera, wireless Internet, and a variety of other functions and services. Also, in addition to the above-described added capabilities, mobile communication terminals that use graphically appealing icons are increasingly being produced.
However, due to the main requirement of retaining portability, mobile communication terminals have a necessary size restriction for their displays (such as an LCD, etc.), so that the sizes of the icons outputted on the display are also restricted.
In order to solve the above problem, one scheme provides that when an icon is selected, an image is enlarged to a predetermined distance outward from the icon. However, this method enlarges the image only partially at the selected location, so that when one wishes to enlarge an image at another location, the location for the image to be enlarged must be changed and selected again. This method, however, can only be applied to mobile communication terminals with touch screen displays.
Accordingly, an apparatus and method capable of enlarging and moving a displayed image on the screen, and allowing the entire content of the image to be displayed on the screen, is required.

Apparatus and method for display control in a mobile communication terminal


A paddle board with flexible extended leads is provided. The paddle board includes a chassis and a flexible lead portion. The flexible lead portion has wire traces disposed therein for receiving a plurality of wires from a parametric test head. The paddle board may be connected to a socket of a testing assembly for testing the performance of a batch of storage media. The paddle board reduces the amount of damage or breakage to the wires extending from the testing head.

The present invention relates generally to testing equipment for rigid discs, and more particularly to a terminal connector for use with a magnetic recording head.
The demand for reliable, accurate and cost effective testing of rigid discs exists throughout the disc manufacturing industry. The rapid growth and technological innovation in the disc manufacturing industry over the last several years has created a demand for testers capable of accurately testing and evaluating the mechanical and read/write performance of the disc. The demand is particularly high in Lot Acceptance Testing (LAT), where a numerous amount of discs are tested in one batch prior to shipment to the disc supplier.
Several tests are known which verify the performance of a rigid disc, for example, a magnetic disc. One such test is glide height testing. This test verifies the mechanical performance at the surface of the disc. For example, defects such as blistering on the disc substrate may be found. Another known test is the certification test. In this test, the integrity of the magnetic layer is determined. For example, it is determined whether the magnetic layer can read or write data precisely and accurately to the desired threshold. In the glide height and certification tests, pre-designed testing heads are used. In particular, when these heads are manufactured, they are equipped with a pre-specified mechanical and wire configuration such that they are easily adapted to the disc testing equipment.
Another well-known test is parametric testing. Parametric testing determines the performance of the disc, for example, the signal-to-noise ratio of the recorded signals on the disc.
Generally in parametric testing, a signal is supplied as an input to the disc being tested in order to measure or determine an output signal. The output signal may be amplified in order to determine or monitor a characteristic of the tested item. In parametric testing, there is an AC (alternating current) and a DC (direct current) test.
In DC testing, the signal input and output vary over a broad dynamic signal range, but at relatively slow speeds. In this test, the transmission of signals is typically subject to problems such as line losses, extraneous signal pick-up, and ground and temperature differentials. In AC testing, the output and input signals operate over a narrow dynamic range, and at high speeds. Typically the output signal is affected by factors such as line loading and impedance effects.
Parametric testing heads are typically the same heads that are used in a head-disc assembly of a disc drive. These heads are manufactured in high volume with a given mechanical configuration and wire length. Thus, in many cases, the wire length is too short to connect with the testing assembly used in the parametric testing procedure. As a result, the wires are extended by splicing or adding additional wire. This splicing process can be expensive and may cause wire damage, breakage, or poor performance in the product head. In addition, such wires cause the input/output signals to suffer from the above-mentioned problems such as line loading and impedance effects.
During testing, the parametric heads are used to statistically test each loader disc prior to shipment, and also on receipt by the drive manufacturer. If the statistical sample passes a set of predetermined criteria, the entire lot is accepted or rejected. If a poor performing head is used, the lot may be rejected inadvertently. This results in the waste of magnetic discs, and adds to the manufacturer""s cost.
One method of extending the wire length of product heads is to solder an additional wire to the head. Another known method is to wirebond the wires to a flex circuit. One disadvantage to these methods is that the wire is easily broken (i.e., the wire is commonly 0.002 in diameter) causing the head to malfunction. In addition, protective tubing normally traverses the length of the wire. In the above methods, this tube must be removed which exposes the wire, thereby increasing the chance of the wire being damaged.
In general, the present invention is directed towards a paddle board having a flexible leads for connection to a plurality of wires of a testing head. The paddle board includes a chassis and a flexible lead portion. A plurality of wire traces are formed onto the paddle board to receive the plurality of wires from the testing head.
Accordingly, in one aspect, the paddle board includes a first portion and a second portion. A plurality of pads are formed on the first portion. The plurality of wire traces are formed onto the first and second portion to receive the plurality of wires from the testing head.
Implementations of the invention include one or more of the following. The first and second portion may be fabricated from the same material, for example, Kapton(trademark) or polyimide. The pads may be formed from gold, silver or copper. A second material may be added to the paddle board to increase its stiffness. A plurality of holes may be formed in the first portion. The plurality of wires from the test head may be attached to the wire traces by ultrasonic bonding, soldering, or thermo-compression. The test head may be an inductive head, a magneto-resistive head or a giant magneto-resistive head. The first portion may be connected to a testing system. One of the plurality of wire traces may transmit a read signal or a write signal between the test head and the testing assembly.
In another aspect, the invention is directed to a testing system which includes a testing assembly having a socket and a test head. A first portion of the paddle board is connected to the socket and a second portion of the paddle board is connected to the wires of the test head.

Paddle board with extended flexible leads


Disclosed is a toilet seat cover closure device responsive to the flow of water in a toilet tank during a flushing operation to operate a push pin to urge the cover from a substantially vertical position to a horizontal position over a toilet seat on a toilet bowl. In a first embodiment the push pin is operated by a bowden wire in response to the pressure of water filling the water tank. In a second embodiment the push pin is operated by a cable arrangement responsive to the lowering of the water in the toilet tank during the first part of the flushing operation. With both embodiments a dampening mechanism is provided to control the rate of descent of the cover, comprising a spring-biased cam element cooperating with cam faces on the cover pivot shaft connected to move with said cover. Also disclosed are quick release fasteners involving deformable elastic members which lock or release the toilet seat and the toilet seat cover to or from the toilet bowl without the need for tools, whereby the toilet seat and toilet cover may be quickly and easily removed for cleaning or replacement.

1. Field of the Invention
This invention relates to a device for closing a toilet seat cover, activated by the flushing of the toilet, and more particularly to a closure device which automatically lowers a fully raised toilet seat cover in a controlled manner when the user thereof actuates the flushing handle.
For safety reasons, it is desirable to have the toilet seat cover and seat in a closed position after use to prevent small children, pets and household articles from falling into the toilet. Even adults may be subjected to inconvenience, trauma, possible injury, and understandable irritation in attempting to use a toilet in the dark, thinking the seat is down when it is not. Additionally, it is esthetically desirable to have the toilet seat and cover in a closed position when not in use. The present invention provides a means for automatically closing the toilet seat cover upon activation of the toilet flushing lever, thereby insuring that both the seat and cover are in a closed position when not in use.
2. Description of Related Prior Art
Toilet seat cover closing devices are well known in the prior art. Also well known in the prior art are counterbalancing devices whereby the lowering of the seat and/or cover is at a controlled rate to minimize noise and/or damage to the seat and/or cover.
U.S. Pat. No. 1,907,826 issued May 9, 1933 to David Kapp discloses a mechanical arrangement actuated by the toilet flushing lever for releasing a catch holding a toilet seat cover in the open position, thereby allowing the toilet seat cover to fall in a controlled manner to the closed position, the control structure comprising a cam rotatable with the cover and acting against a leaf spring. There is no disclosure therein of water pressure or flow being used to initiate closure of the cover.
U.S. Pat. No. 4,402,092 issued Sep. 6, 1983 to Larry L. Smallwood discloses a spring mechanism for toilet seats which uses both a torsion spring and a friction clutch to lower a toilet seat from an upright position at a controlled rate of angular velocity. No structure is disclosed to automatically lower the seat and cover upon flushing of the toilet.
U.S. Pat. No. 4,491,989 issued Jan. 8, 1985 to John F. McGrail discloses a closure device which automatically releases and lowers a toilet seat or the seat and its associated cover together when the flushing handle of a commode or toilet is actuated. The device includes a releasable hinge-closing mechanism having a spring-biased latching lever and a dampening device mounted to the toilet cover. When the latching lever is actuated by the flushing of the commode, the seat or the seat and cover together are released and will move downwardly in a controlled manner by means of the dampening device. A latching pawl is located between the cover hinge member and the seat, whereby the seat and cover are coupled together when in a raised position so as to be lowered together upon being released. The dampening device comprises a cylinder member having means to move air from one chamber to another under pressure, thereby allowing the cover to be lowered at a controlled rate.
U.S. Pat. No. 4,639,147 issued Jan. 27, 1927 to Edward L. Schwarz discloses a friction pivot assembly which may be used with a toilet bowl lid to keep it from inconveniently falling down. The dampening structure includes friction bushings. There is no disclosure by Schwarz of any mechanical means to close the toilet lid.
U.S. Pat. No. 4,912,783 issued Apr. 3, 1990 to Steven E. Shafer discloses a toilet lid closing device for use on toilets of the type having a vertical tank with a flushing lever, a bowl, a seat and an overlying lid. As disclosed, a cable activated by the toilet flushing lever releases a locking means holding the lid upright, and an air cylinder provides a dampener controlling the lowering of the lid.
U.S. Pat. No. 4,914,757 issued Apr. 10, 1990 to Ortiz W. Johnson discloses an automatic toilet lid/seat control device which locks the lid or lid and seat in the upright position when in use and automatically lowers them gently when flushed. Dampening is achieved by means of a fluid cylinder connected to the lid, which starts its descent in response to operation of a flushing handle which depresses a flush rod connected to the lid.


A litter collecting bag is retained by a clamping device in an open-end of a tubular housing. Pawl means attached to a spring loaded handle slidingly mounted atop the housing engages a sliding toothed rod connected through the housing to the clamping device permitting the litter collecting bag to be drawn into an ejected from the housing. When the collecting bag is pressed by the housing onto a quantity of litter, the litter is driven into the collecting bag. The litter bag self-seals as it is fully retracted into the tubular housing and may be discharged later to dispose of the litter conveniently.

In many densely populated urban centers, most notably in New York, public pressure has resulted in recently enacted statutes which require the pet owner to clean up after his pet. This legislation has created a need for a convenient litter retrieving device which allows the pet owner to remove the offensive material with a minimum of effort and to do so as remotely as possible. Devices which are currently available have many drawbacks in their use. They cannot be used after the pet has littered without stooping. The danger exists that the litter would soil the retriever, his clothes, or unintended portions of the retrieving device. Disposal of the litter and/or litter bag again presents an opportunity to befoul oneself. The prior art litter devices generally require use of both hands to effect retrieval of the litter. Previous devices also develop odors if the retrieved litter could not be disposed of immediately after use. Notwithstanding the array of currently available pet litter retrieving devices, there remains a need for a simple, efficient device which eliminates these failings of the prior art.


A device and method for moving cargo on inclined, horizontal or vertical surfaces utilizes frictional forces selectively applied through the use of induced mechanical vibrations on a loaded, platform in conjunction with the force of gravity acting on the platform. The platform is vibrated to pivot or shift the platform relative to a support structure, engaging a portion of the platform secured to the platform with the support structure. At the furthest extent of this motion, the platform is pulled against the support structure by gravity, disengaging the portion from the support structure. In turn the pivot point for the device is shifted to the point of engagement between the platform and the support structure, which enables the portion of the platform to move upwardly along the support structure. The alternation of this engagement of the platform with the support structure causes the platform to move along the support structure.

Known transport devices that can move around freely on oriented surfaces are disclosed in Russian Patent No. NQ2042558 which contains two platforms connected to each other. The first platform is provided with indexing mechanism and is designed as a horizontally mounted thereon cylinders. At the ends of the rods, pneumatic cylinders installed sliding support with lifting and lowering devices. The second vacuum gripper is provided with a platform mounted on the support member and provided with a mechanism for rotation of the platform about a vertical axis.
The disadvantages of this design is its complexity, poor performance, low maneuverability and mobility. This is due to the presence of special gear design, which provides a change of direction, the four pneumatic cylinders. Furthermore, the presence of the electric motor in the turning mechanism weigh down the whole structure.
Another example of a invention in the field of the invention is disclosed in Russian Patent No. NQ2042559. The disclosed device comprises a housing and a stepping movement mechanism which is designed as a bilateral cylinders. These cylinders are arranged perpendicular to each other and connected with each other and the housing, and a sliding bearing. The disadvantages of this device are the complexity of design, large dimensions, weighting device (four air cylinder), a large number of units of the air distribution system, complex design device management system.
To solve the technical problem in the prior art, the invention lies is a design and implementation of a fundamentally new way of lifting and moving a vibrating load platform for an inclined, vertical and horizontal support surface as a result of the interaction of a vibrating platform loaded with a ballast weight with a support structure.
A device for cargo moving on inclined, horizontal and vertical surfaces utilizes frictional forces selectively applied through the use of induced vibrations on a loaded platform in conjunction with the force of gravity acting on the platform. The platform is vibrated in a manner that pivots or shifts the platform relative to a support structure, engaging a portion of the platform secured to the platform with the support structure. When the portion is engaged with the support structure, the vibrations of the platform cause the platform to move upwardly relative to the support member, with the platform portion functioning as a pivot point for the movement. At the furthest extent of this motion, the platform is pulled against the support structure by gravity, disengaging the portion from the support structure. In turn the pivot point for the device is shifted to the point of engagement between the platform and the support structure, which enables the portion of the platform to move upwardly along the support structure. The alternation of the engagement of the platform and portion with the support structure caused by the vibration of the platform in this manner causes the platform to move along the support structure.

Lishanski vibrating transport device and associated method for movement of objects on vertical, horizontal and inclined basic surfaces


A platelet/leukocyte interaction assay method and reagent therefor are provided using the presence of a solid-phase stimulus, such as magnetic or non-magnetic particles or mixtures thereof, having bound to the surface thereof one or more ligands that interact directly with platelets, leukocytes or both, for providing a fast, reliable point-of-care assessment of platelet/leukocyte interaction.

1. Field of the Invention
The present invention relates to a platelet/leukocyte interaction assay allowing for point of care assessment of interaction of platelets and leukocytes, and the reagents therefor.
2. Discussion of the Background
Platelets are known to interact with leukocytes both as a consequence of contact during normal blood flow (Stone and Nash, British Journal of Haematology, 105:514-22, 1999; Lorenz et al, Blood Coagulation and Fibrinolysis, 9:S49-59, 1998) and as a consequence of various pathological processes (Rinder et al, Journal of Cardiovascular Surgery, 118:460-6, 1999; Pevton et al, Journal of Vascular Surgery, 27:1109-15, 1998; Stuard et al, International Journal of Artificial Organs, 21:75-82, 1998; Gawaz et al, European Journal of Clinical Investigation, 25:843-51, 1995).
Pathological conditions such as Unstable Angina, Coronary Artery Disease (CAD), and Stroke are characterized by high levels of platelet and leukocyte activity. Measurement of platelet/leukocyte interaction can be predictive of these pathological states, particularly in combination with other diagnostic factors. Also, measurement of platelet/leukocyte interaction can be used as a means of monitoring therapy directed toward altering platelet and/or leukocyte function.
Exposure of flowing blood to artificial surfaces has been shown to enhance platelet/leukocyte interaction. The cell types involved and the extent of the interaction vary with the composition of the artificial surface in contact with the blood (Gawaz et al, Artificial Organs, 23:29-36, 1999).
Although platelet/leukocyte interactions have been quantified using various techniques (Hendricks et al, U.S. Pat. No. 5,503,982; Rinder et al, Blood, 78:1760, 1991;), assessment of the interaction has relied upon measurement of circulating platelet/leukocyte complexes. Measurements, to date, have taken the form of evaluating pre-existing platelet/leukocyte interactions in a blood sample.
In some pathological conditions (e.g. Acute Myocardial Infarction, AMI; post Angioplasty, PTCA; etc.) platelet/leukocyte complex formation is associated with interaction with damaged subendothelium, whether directly (plaque formation) or indirectly (release of biochemical markers such as ICAM-1, see Hendricks et al, U.S. Pat. No. 5,503,982).
Current assay systems used to assess platelet/leukocyte interactions, as exemplified by Hendricks et al (U.S. Pat. No. 5,503,982), evaluate pre-existing (circulating) platelet/leukocyte complexes and do not utilize a component representative of the vessel subendothelium (i.e. extracellular matrix) or other solid-phase stimulus. Moreover, the threshold at which discrete platelets and leukocytes interact could vary depending on the activation status of these cells at the time of testing. It is known in the art that platelet and/or leukocyte activation is a necessary prerequisite of platelet/leukocyte binding. It is also known in the art that certain pathological conditions are associated with upregulation of platelet and/or leukocyte activity. However, the upregulation in cellular activity associated with the pathological process may be insufficient to support platelet/leukocyte complex formation without additional stimulation and moreover, may not be detectable using conventional systems, which lack a stabilizing solid-phase support upon which the platelet/leukocyte complex could be maintained. (A solid-phase stimulus could be used as a means of localizing pre-existing platelet leukocyte complexes and/or inducing complex formation and localization in cells predisposed to do so.)
It is desirable that assay systems designed to incorporate the use of a solid-phase component such as immobilized subendothelial/extracellular matrix be facile, rapid and of reasonable cost to be useful in detecting platelet/leukocyte interaction in a clinical setting.
The present invention addresses shortcomings of previous methods and technologies by using microparticles of various compositions coated with plasma proteins and/or extracellular matrix proteins, either singly or in combination, to facilitate rapid assessment of platelet/leukocyte binding.
Platelets can interact with leukocytes through various mechanisms, such as contact during normal blood flow (Lorenz et al, Blood Coagulation and Fibrinolysis, 9:S49-S59, 1998), or as a consequence of a pathological process associated with platelet hyperactivity (Spanygenberg, Thrombosis Research, 74:S35-S44, 1994; Rinder et al, Journal of Cardiovascular Surgery, 118:460-6, 1999) or due to an inflammatory process (Gawaz et al, European Journal of Clinical Investigation, 25:843-51, 1995). Receptors found on the platelet surface interact with receptors found on various leukocytes through direct bridging or through an indirect linkage involving intermediary molecules (Weber and Springer, Journal of Clinical Investigation, 100:2085-93, 1997). Upregulation of platelet and/or leukocyte activity favors enhanced platelet/leukocyte interaction (Rinder et al, 1999; Stone and Nash, British Journal of Haematology, 105:514-22, 1999; Konstantopoulos et al, 1998; Gawaz et al, 1995; Spanenberg, 1994).
Individuals with Coronary Artery Disease (CAD), Diabetes or Cerebrovascular Ischemia demonstrate both platelet hyperactivity and an ongoing inflammatory process (Michelson and Furman, Current Opinion in Hematology, 6:342-8, 1999). Treatment of patients with CAD has involved the use of anti-platelet agents and anti-inflammatory medications (Vorchheimer et al, JAMA 281:1407-14, 1999; Mannaioni et al, Inflammation Research, 46:4-18, 1997).
Platelet/monocyte (Hendricks et al, U.S. Pat. No. 5,503,982) and platelet/neutrophil (Gawaz et al, European Journal of Clinical Investigation, 25:843-51, 1995) interaction have been suggested to be predictive of acute myocardial infarction (AMI) and inflammation, respectively. A corollary to platelet/leukocyte interaction in various pathological conditions is involvement of the vessel wall, whether in plaque formation for example, or a localized inflammatory reaction.
Platelet function assessment using immobilized extracellular matrix proteins has been described by Shaw and Stewart (U.S. Pat. No. 5,427,913). The authors demonstrated that von Willebrand factor (VWF) immobilized on polystyrene beads could be used to activate platelets and thereby determine the functional status of platelets from patients with platelet function defects. In addition, the authors also demonstrated that the effects of agents designed to alter platelet function could be monitored using bead-immobilized VWF as a stimulus. The results of these studies underline the importance of evaluating a normal hematological interaction or the hematologic consequence of a pathological state in the presence of an agent that mimics components of the vessel wall.
Although Shaw and Stewart describe methods and compositions of determining platelet function, there is no description or suggestion of using their method for evaluating platelet/leukocyte interaction.
CVDI""s TAS(trademark) analyzer measures the kinetics of fibrin polymerization following activation of the coagulation pathway in a patient""s blood sample. The TAS(trademark) analyzer and disposable were designed for use with whole blood in a point-of-care setting. Paramagnetic iron oxide particles (PIOP) are an essential component of the detection system for each of the tests developed for the TAS(trademark) analyzer. The PIOP and other lyophilized ingredients for a particular test are located in the shallow reaction chamber of the TAS test card disposable. In addition to PIOP, the test reagent may contain buffers, stabilizers, fillers and specific coagulation pathway activator or agents. A test is initiated by insertion of a dry-chemistry test card into a slot of the TAS(trademark) analyzer that automatically positions the test card reaction chamber above an electromagnet. This chamber is also illuminated with infrared light from a light emitting diode. The instrument measures reflected infrared light from the surface of the test card by means of a solid state photodiode detector. A test is automatically initiated when the analyzer photodetector measures a change in reflected light intensity when blood or plasma is added to the sample well of the test card and, through capillary action, is pulled into the reaction chamber. The activators present in the reaction chambers stimulate the coagulation cascade in the patient""s sample to produce thrombin, which in turn catalyzes the formation of the fibrin clot.
During a clotting test the TAS(trademark) analyzer electromagnet oscillates on and off every second. The magnetic particles stand up when the electromagnet is on, causing more light to be reflected to the detector, and fall down when it is off, causing less light to be detected. This movement of PIOP produces an alternating current (AC) signal from the photodetector. As the test proceeds, more and more fibrin polymerization occurs and the PIOP movement is less. The analyzer in accordance with predetermined algorithms interprets the signal produced by the relative movement of the PIOP and reports an endpoint (clotting time) appropriate for each test.
Although PIOP is an integral component of the TAS(trademark) detection system, it does not participate directly in activation of the coagulation cascade or fibrin polymerization. To prevent undesired interactions between PIOP and activators within the reaction chamber of a test card, the PIOP is coated or blocked with bovine serum albumin (BSA). BSA is a protein commonly used by those skilled in assay development to prevent unwanted interactions between surface components of a test and its active ingredients. The TAS(trademark) system was designed to monitor fibrin polymerization and not interactions between platelets and leukocytes.
Accordingly, one object of the present invention is to provide an assay for platelet/leukocyte interaction that can be used with a variety of blood products as the sample, including whole blood, with ease of detection.
A further object of the present invention is to provide an assay for platelet/leukocyte interaction that can be used on the TAS(trademark) system for rapid determination of platelet/leukocyte interactions.
A further object of the present invention is to provide a platelet/leukocyte interaction assay reagent, preferably in a dry chemistry test card format that can be used in the assay of the present invention.
A further object of the present invention is to provide a method for diagnosis of conditions resulting in platelet/leukocyte interactions using the assay of the present invention.
A further object of the present invention is to provide a method for determination of platelet and/or leukocyte hyperactivity using the assay of the present invention.
These and other objects of the present invention have been satisfied by the discovery of a method of assessing platelet/leukocyte interaction, comprising:
contacting a whole blood or blood-derived sample with a solid-phase stimulus, wherein said solid-phase stimulus has bound to a surface thereof a ligand selective for binding platelets or leukocytes, and
detecting formation of one or more platelet/leukocyte/solid-phase stimulus complexes, and the reagents for performing the method, as well as the use of the method for detection of the occurrence of platelet/leukocyte interaction caused by various disease conditions and the predisposition of subjects to those conditions.

Platelet/leukocyte interaction assay and reagent therefor


An improved electrostatic coalescence system is provided in which independent AC and DC hydrophilic electrodes are employed to provide more complete dehydration of an oil emulsion. The AC field is produced between an AC electrode array and the water-oil interface wherein the AC electrode array is positioned parallel to the interface which acts as a grounded electrode. The emulsion is introduced into the AC field in an evenly distributed manner at the interface. The AC field promotes drop-drop and drop-interface coalescence of the water phase in the entering emulsion. The continuous oil phase passes upward through the perforated AC electrode array and enters a strong DC field produced between closely spaced DC electrodes in which small dispersed droplets of water entrained in the continuous phase are removed primarily by collection at hydrophilic DC electrodes. Large droplets of water collected by the electrodes migrate downward through the AC electrode array to the interface. All phase separation mechanisms are utilized to accomplish more complete phase separation.

This invention relates generally to systems for removing water from an oil emulsion by electrostatically promoting coalescence of water droplets into sizes large enough to gravitate from the oil. More specifically this invention relates to an improved electrostatic coalescence system for separating a dispersed water phase from a continuous oil phase in which independent AC and DC electric fields are employed together with hydrophilic electrodes to take advantage of a number of phase separation mechanisms to accomplish more complete phase separation.
In the petroleum industry electrostatic coalescence techniques have been employed for resolving water-in-oil emulsion. Generally, an AC electric field is used when the electrical conductivity of the continuous oil phase is between 10.sup.-8 to 10.sup.-10 ohm.sup.-1 cm.sup.-1, and a DC electric field is used when the electrical conductivity of oil is less than 10.sup.-10 ohm.sup.-1 cm.sup.-1. The conductivity is generally dependent on the amount of water in the crude oil.
Not only is water present naturally in crude oil, but water is added and vigorously mixed with crude stock to aid in the process of desalting of the crude prior to refining. Desalting is a process in which salts, water and solid particles are removed from the crude oil through the separation of the salt and solid-laden water phase from the continuous oil phase. The presence of salts, water and solids in crude causes various problems in the operation of an oil refinery. It causes the formation of sludge in crude storage tanks which reduces the storage capacity. Sludge may also accumulate in distillation columns and cause serious operation problems. Salt deposition in equipment such as heat exchanger tubes in crude furnaces leads to plugging and fouling of the process equipment. Salts also catalyze the formation of coke in the furnace. Coke deposition reduces the heat transfer coefficient, causing localized heating and eventually leading to blistering or rupture of the tubes.
Further, salts in crude oil cause corrosion because they lead to evolution of hydrochloric acid in distillation equipment. The severe corrosion from the combination of sulfur-containing compounds with hydrogen chloride, is caused by oxidation reduction reactions. The units most susceptible to corrosion from hydrogen chloride are those where moisture may be present, such as in condensers.
When the crude feed contains salts, the solubility and ductility of asphalt products can be affected. Salts also cause fuel oil to have excessively high ash content. Gas turbine fuel must be salt-free, otherwise fused salts can seriously damage the turbine blades.
Thus, it will be seen that salts in crude oil must be removed prior to charge into crude distillation units. Water and solid particles are also removed as the result of extraction of salts with water. It has been recognized in the art that the fastest method of water extraction from crude feed is through the use of electrostatic coalescence methods.
Generally, systems employing electrostatic coalescence methods have used either DC or AC electric fields only. One system is known in which a pulsed DC field is employed to simulate a combination AC and DC coalescing system. Details of this system may be had by referring to the following patents:
1. U.S. Pat. No. 3,772,180 issued to Floyd L. Prestridge for "Electric Treater," Nov. 13, 1973.
2. U.S. Pat. No. 3,847,775 issued to Floyd L. Prestridge for "Process for Electrical Coalescing of Water," Nov. 12, 1974.
Briefly, the referenced system employs a single set of electrodes mounted above the emulsion-water interface in the treater containment. The positive and negative electrodes are alternately pulsed to produce a generally uniform DC field between the electrodes and a simulated non-uniform AC field between the electrodes and the interface which acts as a ground electrode. The field gradients vary depending upon the dispersed phase volume fraction of the emulsion introduced at the interface. Thus, since the AC and DC fields are produced using common electrodes, the dispersed phase volume entering the DC field region controls both the AC and DC field components. Non-uniformity in the fields can cause very high localized electric field gradients which produce water droplet breakup, redispersing the water phase and reducing the efficiency of the unit. Further, the AC and DC fields cannot be independently controlled for selected AC and DC electric field gradients for most efficient operation. The DC electrode spacing is dictated by spacing requirements for producing the simulated AC field. For more complete phase separation it has been found that the spacing between the DC electrodes, through which the continuous oil phase passes after the bulk of the water is removed by the AC electrodes, should be small to provide short drop residence time required for the removal of small dispersed water drops from the continuous oil phase. This allows collection of small drops of water at hydrophilic electrodes which is the primary DC phase separation mechanism of the present invention. Drop-drop coalescence, settling of coalesced drops, and drop contact charging are secondary phase separating mechanisms provided by the independent DC electrode arrangement contemplated by the present invention.
Therefore, it is an object of the present invention to provide an improved electrostatic coalescence unit for removal of water dispersed in crude oil with independent AC and DC electrode structures which provides more complete separation.
Yet another object of this invention is to provide an electrostatic coalescence unit as set forth in the above object in which multiple-phase separation mechanisms are utilized to enhance more complete phase separations.
Other objects and many of the attendant advantages of the present invention will be obvious to those skilled in the art from the detailed description of the invention which follows hereinbelow.

Electrostatic coalescence system with independent AC and DC hydrophilic electrodes

The United States of America as represented by the United States Department of Energy


An inductive plasma applicator comprises a ferromagnetic inductively coupled source and an electrode with a hole pattern centered with respect to the plasma source. Such plasma applicator provides an efficient energy transfer to the plasma. The plasma applicator is preferably manufactured using a technology for producing electrical circuits. The electrode and a coil of the ferromagnetic inductively coupled plasma source are metal track portions formed on an insulating substrate. For example, the plasma applicator is manufactured using printed circuit board technology.

The present invention relates to an inductive plasma applicator, a vacuum vessel comprising this inductive plasma applicator, and a surface treatment device comprising the vacuum vessel.
Plasma treatments are widely used in the industry for many purposes, such as surface activation, in particular for polymer-based materials, material thin film deposition, layer etching, etc. Many applications also require that the plasma treatments are performed on large area substrates, ranging from about one square-centimeter to several square meters. For example, architectural glazings implement thin film stacks that are deposited on glass panels of about 20 square-meters. Thin film stacks are also deposited on continuous polymer-based sheets in roll-coaters.
According to a well-known implementation mode of plasma treatments, the plasma is energized with a RF frequency magnetic field. The magnetic field is produced in a plasma volume using a coil which is supplied with an AC current. The AC magnetic field produces in turn an electric field which transfers energy to the plasma.
Actually, a processing time for such plasma treatment depends on physical parameters of the plasma which is implemented. For example, the magnetic field in the plasma volume is an important parameter, as well as the separating distance between the surface to be treated and the location where the plasma density is the highest. So, a plasma treatment device should be designed taking into account values for such parameters which are optimized for the treatment and the application of concern. Therefore, there is a need for supplying plasma treatment devices with design and geometry parameters which can be varied easily on order.
Another need relates to large area plasma sources, which are suitable for performing uniform treatments of wide substrates. In particular, such large area plasma sources should be suitable for implementation in vacuum devices  with fixed or moving substrates.
A further need is to provide plasma generating devices which are suitable for being installed easily in many vacuum vessels, with short installation time.
A further need is also to provide plasma generating devices with unit cost which is reduced with respect to the plasma sources currently available.
Therefore, an object of the present invention is to provide a plasma source which meets at least one of these requirements.

Centre National de la Recherche Scientifique-CNRS


Detectable warning areas (DWAs) and methods of forming the same are provided. A mat template having one or more holes can be placed over a substrate, and a dome-forming material can be filled in the mat template by pouring the dome-forming material over the mat template and working the dome-forming material into the one or more holes of the mat template. The mat template can remain in place until the dome-forming material is completely cured, and then the mat template can be removed. DWAs formed according to this method display improved properties, including increased bond strength.

Detectable warning areas (DWAs) are integral surface features built in or applied to walking surfaces or other elements to warn individuals with visual impairments of hazards on a circulation path. DWAs are often standardized and typically include raised features, such as domes. DWAs are generally found along a sidewalk, near a curb, before a road or door at an airport or train station, or along other circulation paths.
Truncated domes are a uniform standard that have been chosen by the federal government over all others as the only approved surface texture allowed under specified criteria such that "continuity" of design for the visually impaired is maintained. According to the Americans with Disabilities Act Accessibility Guidelines (ADAAG), truncated domes are to be placed around hazardous vehicular ways, access ramps, transit platform edges, and where predetermined edge protection is required.
Existing methods to form DWAs include using an epoxy-based dome material in a relatively rigid, re-usable template made of hard rubber. The dome material is applied to the template using a squeeze bottle, and then the template is removed almost immediately and the dome material is allowed to cure after the template is removed. While curing, the dome material can rise, such that it no longer takes the same shape as the template.

Advantageous detectable warning area and methods of forming the same


Disclosed are compounds useful as inhibitors of the Wnt signalling pathway. Specifically, inhibitors of Porcupine (Porcn) are contemplated by the invention. In addition, the invention contemplates processes to prepare the compounds and uses of the compounds. The compounds of the invention may therefore be used in treating conditions mediated by the Wnt signalling pathway, for example, in treating cancer, sarcoma, melanoma, skin cancer, haematological tumors, lymphoma, carcinoma, and leukemia; or enhancing the effectiveness of an anti-cancer treatment.

The Wnt genes encode a large and highly conserved family of secreted growth factors. During normal development, transcription of Wnt family genes is tightly regulated both temporally and spatially. To date, 19 Wnt proteins have been discovered in humans. All of the Wnt proteins are 38- to 43-kDa cysteine-rich glycoproteins. Wnts have a range of roles during development, governing cell fate, migration, proliferation and death. These include body axis formation in zebrafish and xenopus, wing and eye development in drosophila and brain development in mice (Parr, et al. (1994) Curr. Opinion Genetics & Devel. 4:523-528, McMahon A P, Bradley A (1990) Cell 62: 1073-1085). In adults the role of Wnts is thought to be linked to maintaining tissue homeostasis with aberrant signalling implicated in a variety of cancers.
Wnt-mediated signalling occurs through binding of Wnt ligand to frizzled (Fzd) proteins, seven-transmembrane receptors. These receptors contain an N-terminal cysteine rich domain (CRD) which serves as the Wnt binding domain. Binding is stabilised by low-density-lipoprotein receptor-related proteins 5 and 6 (Lrp5 and Lrp6) (He, et al. (2004) Dev April; 131(8):1663-77). Fizzled ligation by Wnt is known to activate at least three different signalling pathways including the "canonical" β-catenin pathway, "non-canonical" planar cell polarity (PCP) and calcium pathways. Wnt signalling is further regulated by alternative receptors, including Ror2, secreted antagonists, such as WIF-1 (Hsieh, et al. (1999) Nature April 1; 398(6726):431-6) and alternative Wnt receptors, such as Dickkopf (DKK) (Niehrs C (2006) Oncogene December 4; 25(57):7469-81).
When inactive, β-Catenin is rapidly turned over by a conglomeration of several proteins known as the "destruction complex". The complex consists of Axin, adenomatous polyposis coli (APC), casein kinase (CK)-1a and glycogen synthasekinase (GSK)-3β (Hamada, et al. (1999) Science 12; 283(5408):1739-42). In this state, β-catenin is phosphorylated on serine-threonine on the amino terminus leading to ubiquitination (Behrens, et al. (1998) Science 280: 596-599). In the canonical pathway of Wnt activation, Wnt-ligated Fzd binds to and activates cytoplasmic Dishevelled (Dvl) (Chen, et al. (2003) Science 301:1391-94). Wnt-ligated Lrp5 and Lrp6 directly bind to cytoplasmic Axin, inhibiting its function as a destruction complex stabiliser (Zeng, et al. (2008) Dev. 135, 367-375). These associations lead to a destabilisation of the destruction complex and cytosolic accumulation of β-catenin. Stabilisation and accumulation of β-catenin leads to nuclear translocation where it complexes with T cell factor/lymphoid enhancer factor (TCF/LEF) high mobility group transcription factors and promotes transcription of target genes such as Cyclin D1, p21 and cMyc.
Oncogenic mutations in the β-catenin gene CTNNb1 exclusively affect specific serine and threonine and surrounding residues vital for targeted degradation by APC (Hart, et al. (1999) Curr. Biol. 9:207-210). This interaction is especially apparent in colorectal cancer, where the majority of tumours present with APC mutations and an increased proportion of the remainder express CTNNb1 mutations (Iwao, et al. (1998) Cancer Res Mar. 1, 1998 58; 1021).
Many recent studies have investigated compounds targeting β-catenin or other downstream Wnt pathway proteins. Recent research suggests that modulating Wnt-Wnt receptor interaction at the cell surface is effective in reducing cell oncogenicity. This has been shown in systems with tumourgenicity driven by Wnt ligand overexpression (Liu, et al. (2013) PNAS 10; 110(50):20224-9) and where Wnt expression is driven by downstream pathway activation (Vincan et al., Differentiation 2005; 73: 142-153). Vincan et al transfected non-functional Frd7 receptor into a SK-CO-1 cell line with a homozygous APC mutation driving Wnt pathway activation. These cells demonstrated modulated morphology and reduced tumour-forming efficiency compared to parental cells in a xenograft model. This data suggests that modulating Wnt ligand-mediated signalling may have a beneficial effect even in malignancies with downstream Wnt pathway mutations.
The described invention is proposed to inhibit Wnt-mediated signalling. This includes paracrine signalling in the tissues surrounding tumours and autocrine and paracrine signalling in cancer cells.
Wnt proteins undergo post-translational modification, shown in several mutation experiments to be vital for effective protein trafficking and secretion (Tang, et al. (2012) Dev. Biol 364, 32-41, Takada, R. et al (2006) Dev. Cell 11, 791-801). Palmitoylation of Wnt proteins occurs at several conserved amino acids (C77, S209) and is performed by porcupine, an O-acetyltransferase, in the endoplasmic reticulum. Mutations in porcupine have been shown to be the cause of developmental disorders, including focal dermal hypoplasia, through impaired Wnt pathway signalling (Grzeschik, et al. (2007) Nat. Genet, 39 pp. 833-835). The dependence of Wnt ligand signalling on porcupine and the body of evidence linking Wnt pathway signalling to cancer has led to porcupine being identified as a potential anti-cancer target.
US 2014/0038922 discloses compounds that inhibit the Wnt signalling pathway and the use of these compounds in the treatment of Wnt signalling-related diseases. Similarly, WO 2012/003189 and WO 2010/101849 disclose compounds and methods for modulating Wnt signalling pathway.
An aim of the present invention is to provide alternative or improved Wnt signalling modulators. For example, an aim of the present invention is to provide alternative or improved Wnt signalling inhibitors, optionally inhibitors of porcupine.
Furthermore, it is an aim of certain embodiments of this invention to provide new compounds for use in: Wnt mediated diseases, such as secreted Wnt ligand mediated diseases which may be treated by inhibition of porcupine; treating cancer, sarcoma, melanoma, skin cancer, haematological tumors, lymphoma, carcinoma, and leukemia; or enhancing the effectiveness of an anti-cancer treatment.
It is an aim of certain embodiments of this invention to provide new cancer treatments. In particular, it is an aim of certain embodiments of this invention to provide compounds which have comparable activity to existing treatments, ideally they should have better activity. Certain embodiments of the invention also aim to provide improved solubility compared to prior art compounds and existing therapies. It is particularly attractive for certain compounds of the invention to provide better activity and better solubility over known compounds.
It is an aim of certain embodiments of this invention to provide compounds which exhibit reduced cytotoxicity relative to prior art compounds and existing therapies.
Another aim of certain embodiments of this invention is to provide compounds having a convenient pharmacokinetic profile and a suitable duration of action following dosing. A further aim of certain embodiments of this invention is to provide compounds in which the metabolised fragment or fragments of the drug after absorption are GRAS (Generally Regarded As Safe).
Certain embodiments of the present invention satisfy some or all of the above aims.

N-pyridinyl acetamide derivatives as Wnt signalling pathway inhibitors