A method is provided for diagnosing detrusor instability. The method includes using an insert member having a channel therethrough positioned distal of the urethral sphincter, creating a substantially fluid tight seal to substantially block fluid flow into or out of the urethral canal other than through the channel, infusing fluid from a fluid source through the channel in the insert member and into the urethral canal at a location distal of the urethral sphincter, and measuring a pressure within the urethral canal at a location distal of the urethral sphincter as the fluid is being infused therein. The infusing step further involves infusing fluid until the urethral sphincter opens, and thereafter until at least one detrusor contraction occurs.

Women account for more than 11 million of incontinence cases. Moreover, a majority of women with incontinence suffer from stress urinary incontinence (SUI). Women with SUI involuntarily lose urine during normal daily activities and movements, such as laughing, coughing, sneezing and regular exercise.
SUI may be caused by a functional defect of the tissue or ligaments connecting the vaginal wall with the pelvic muscles and pubic bone. Common causes include repetitive straining of the pelvic muscles, childbirth, loss of pelvic muscle tone and estrogen loss. Such a defect results in an improperly functioning urethra. Unlike other types of incontinence, SUI is not a problem of the bladder.
Normally, the urethra, when properly supported by strong pelvic floor muscles and healthy connective tissue, maintains a tight seal to prevent involuntary loss of urine. When a woman suffers from the most common form of SUI, however, weakened muscle and pelvic tissues are unable to adequately support the urethra in its correct position. As a result, during normal movements when pressure is exerted on the bladder from the diaphragm, the urethra cannot retain its seal, permitting urine to escape. Because SUI is both embarrassing and unpredictable, many women with SUI avoid an active lifestyle, shying away from social situations.
SUI is categorized into three types. Type I and Type II are directed to urethral hypermobility. Type III is directed to intrinsic sphincter deficiency (ISD). Diagnosis of ISD requires urodynamic evaluation. Urodynamic evaluation involves complex and invasive equipment and often requires referral to a specialist trained in urodynamic evaluation.
Existing diagnostic systems all require a catheter be passed trans-urethraly to measure pressure, such as Leak Point Pressure (LPP) or Urethral Pressure Profile (UPP). An exemplary system is disclosed in publication (WO 0023127). Detection of LPP requires that a pressure sensor and catheter be passed trans-urethrally. The bladder is filled, and pressure is recorded. Fluid leakage from the urethral opening (meatus) corresponds to the maximum pressure the urethral sphincter can resist, or LPP. During the UPP measurement procedure a pressure sensor tipped catheter is placed trans-urethral into the bladder and then withdrawn at a constant velocity. The pressure profile along the urethra, from bladder neck to meatus is recorded.
Other parameters may also be measured, such as abdominal pressure and urinary flow. A cystometrogram (CMG) is a pressure study that simultaneously measures intra-abdominal, total bladder, and true detrusor pressures. Uroflometry measures urine flow rate visually, electronically, or via a disposable system. Video Urodynamic Systems also exist that simultaneously measure parameters, as described above, with radiographic visualization of the lower urinary-tract.
Existing urodynamic evaluation systems are complex, expensive, and require extensive training. Furthermore, existing urodynamic systems often require at least 30 minutes to complete a test. This exceeds the time available for most standard physician office visits and results in referral to a specialist. No urodynamic system exists that can quickly and inexpensively record useful urodynamic measures, without passing a catheter or instrument trans-urethraly.
Other than SUI, urge incontinence also accounts for a great number of cases of urinary incontinence. Urge incontinence is caused by overactive bladder muscles. Detrusor instability is one cause of urge incontinence. Detrusor instability involves spontaneous and unprovoked involuntary contractions of the detrusor muscle (the muscles that make up the bladder wall) during filling of the bladder that cannot be suppressed. Currently, diagnosis of detrusor instability similarly involves the use of invasive and uncomfortable transurethral catheters. The bladder is filled with fluid using such catheters, and the pressure is monitored to detects spikes in pressure, which indicate detrusor muscle contractions. Diagnosis using transurethral catheters is often complicated by the fact that the catheter often aggravates the delicate muscle structures of the urethral sphincter and bladder neck. Thus, the transurethral catheter actually aggravates and disrupts the very structures that the measurements seek to evaluate, potentially giving misleading results.
With regard to urge incontinence, there remains a need for an improved system and method for assessing detrusor instability.

System and method for assessing detrusor instability


Methods for lower latency connections using speculative DNS resolution are provided. In one aspect, a method includes receiving a request at a client for a web resource to be sent to a hostname. The method also includes obtaining a speculative Domain Name System (DNS) resolution of the hostname from a source local to the client. The method also includes initiating a connection to the hostname using the obtained speculative DNS resolution of the hostname. Systems and machine-readable media are also provided.

Field
The present disclosure generally relates to the transmission of data over a network, and more particularly to the connection of a computing device with another computing device.
Description of the Related Art
In order for a client to receive content from a hostname, a connection must be established. Establishing a connection on the internet typically requires two steps: resolving a hostname to an IP address, and then contacting the hostname at the IP address to establish the connection. In order to resolve a hostname to an IP address, the client asks a Domain Name System (DNS) resolver for the IP address for a given hostname. Once the client has obtained the IP address, the client is then able to contact the hostname at the IP address to establish the connection.

Lower latency connections using speculative DNS resolution


A surface mount electronic component that includes a resin case, metal terminals, and a sealing metal plate that are molded integrally by insert molding. A hollow casing part and a through hole are formed in the case. The through hole leads from the hollow casing part to a surface of the case. The metal plate seals the through hole. The metal plate has a coefficient of linear expansion that is different from a coefficient of linear expansion of the case so that deformation to unseal the through hole occurs when heated.

With the advancement of high-density mounting in electronic equipment, various surface mount electronic components are used these days. Some electronic component chips need hermetic sealing. To encase such an electronic component chip, a surface mount electronic component including a resin case that has a hollow casing part has been used in the art.
FIG. 8 is a perspective view that illustrates the mounting structure of a surface mount electronic component disclosed in the patent literature (PTL) 1 shown below. A surface mount electronic component 1001 is mounted on a substrate 1002. Electrodes 1003 and 1004 are formed on the substrate 1002. The metal terminals 1005 and 1006 of the surface mount electronic component 1001 are bonded to the electrodes 1003 and 1004 by means of solder blobs 1007 and 1008, respectively. A reflow soldering method is used for the bonding.
The surface mount electronic component 1001 has the following structure: a top cover member 1010 is bonded to an open-topped case body 1009; a bonding material 1011 is sandwiched between the cover 1010 and the case 1009 to fix them to each other. Therefore, the surface mount electronic component 1001 has a casing structure that includes an inner space functioning as a casing space. An electronic component chip that is not illustrated is encased in this hollow casing part. The metal terminals 1005 and 1006 are connected to the electronic component chip.
When the surface mount electronic component 1001 is mounted to the substrate 1002 by using the reflow soldering method, solder is heated to a temperature at which it melts, for example, approximately 260° C. The internal pressure of the surface mount electronic component 1001 increases due to heating. In order to prevent the case from being damaged due to the increase in the internal pressure, a through hole 1012 is formed as illustrated in FIG. 9. The hole 1012 is formed through a sidewall of the case body 1009. The metal terminal 1005 extends from inside the through hole 1012 onto the bottom surface of the case body 1009 by way of the side surface thereof. In the process of the rising of the internal pressure due to heat applied at the time of reflow soldering, air escapes from the inside of the case body 1009 to the outside through the through hole 1012. By this means, it is possible to prevent the internal pressure of the case from increasing significantly. After heating during the process of reflow soldering, the mounted component is allowed to cool to room temperature. In the cooling step, the solder 1007 that is in a molten state hardens. As a result, as illustrated in FIG. 9, the metal terminal 1005 and the electrode 1003 become bonded to each other. Since a part of the solder 1007 in the molten state flows into the through hole 1012, the through hole 1012 gets sealed as a result of the solidification of the molten solder. Therefore, the case that has been subjected to reflow soldering is hermetically sealed.
PTL 1: Japanese Unexamined Patent Application Publication No. 2006-294757


Methods for measuring and controlling the methanol concentration in a methanol fuel cell such as a direct methanol fuel cell or fuel cell stack are disclosed. Processors and memory storage containing programs which execute instructions to control the methanol concentration in the fuel cell or fuel cell stack are also disclosed.

A direct methanol fuel cell (DMFC) has an anode, a cathode and an electrolyte interposed between the anode and the cathode. In fuel cells, electricity is produced from the electrochemical reactions which take place at the anode and the cathode. At the anode, methanol is electrochemically oxidized with water to produce electrons, protons and carbon dioxide. The electrons travel through an external electronic circuit to the cathode. At the cathode, oxygen electrochemically reacts with electrons and protons, which migrate through the electrolyte from the anode to cathode. During these electrochemical reactions, electrons pass through an external circuit and may be used as an energy source for electronic devices. The electrolyte used in the direct methanol fuel cell can be acidic or basic. An acidic proton exchange membrane (PEM) such as the perfluorosulfonic acid (PFSA) membrane Nafion produced by DuPont may be used as an electrolyte for the DMFC.
A DMFC system also has a fuel tank for storing concentrated or pure methanol, and supplies a mixture of methanol and water as fuel to the anode. The methanol can crossover (a phenomenon in which fuel passes through the membrane) through Nafion and other PEMs if the concentration of methanol is high in the mixture. This fuel crossover increases as a function of temperature, concentration of methanol and the thickness of the PEM. For example, higher operating temperature, higher fuel concentration, and thinner (or higher conductance) PEMs increase the fuel crossover rate. The higher fuel crossover causes negative effects on fuel utilization, performance, and durability.
Fuel concentration is an important factor affecting the performance of a fuel cell. Therefore, controlling the fuel concentration is necessary to ensure optimum performance and proper fuel utilization by the fuel cell.
Many methods have been used to determine the concentration of methanol in the mixture of methanol and water which is fed to the anode. In one such method, a small amount of the methanol mixture is separated and heated until boiling, and the boiling point is measured to determine the fuel concentration. Other methods include measuring the capacitance of the methanol mixture, the speed of sound in the methanol mixture, the refractive index of the methanol mixture, the heat capacity of the methanol mixture, the viscosity of the methanol mixture, the kinematic viscosity of the methanol mixture and the electrochemical properties of the methanol mixture. An example of the latter is disclosed in US Patent Publication 2012/0009495.
Many of these methods are time consuming and require the use of complex and/or expensive equipment. Further, the reliability of some of such methods to accurately measure methanol concentration due to potential measurement errors has been called into question. See Investigation of Direct Methanol Fuel Cell Voltage Response for Methanol Concentration Sensing by William J. Harrison, Master of Science Thesis, University of Florida, 2012: http://ufdc.ufl.edu/UFE0044418/00001.
Accordingly, there is a need for methods and means to reliably measure and control the methanol concentration in methanol mixtures in DMFCs in a manner that reduces the cost and complexity of manufacture of the DMFC. An additional benefit of stably controlling the methanol concentration is improved durability of the fuel cell or fuel cell stack.

Method for measuring and controlling methanol concentration in a methanol fuel cell


In various embodiments, a two stage shock strut for use in a landing gear assembly may comprise a first cylinder, a fill port, a first stage piston head, a second cylinder, a second stage piston head, and a bleed tube. The first cylinder may define a first volume. The fill port valve may be in fluid communication with the first cylinder and configured to receive hydraulic fluid. The first stage piston head may be in fluid communication with the first volume. The second cylinder may comprise a metering pin. The metering pin may be in fluid communication with the first volume and a second volume defined by the second cylinder. The metering pin may be configured to receive the hydraulic fluid from the first volume and purge gas from the second volume. The second stage piston head may be in fluid communication with the second volume.

Typically, an aircraft includes landing gear having wheels and shock struts. Many of these shock struts are now dual stage shock struts. These dual stage shock struts may include hydraulic fluid that benefits from servicing from time to time. To service typical dual stage shock struts, the aircraft is lifted above the ground so that the shock strut can be in the fully extended position for servicing. Alternatively, the shock strut may be cycled multiple times in attempt to fully remove any trapped gas internal to the shock strut during servicing. Both of these options are time consuming and costly.

Dual stage shock strut with removable second stage fluid chamber


A computer-implemented method of simultaneously providing a plurality of unique and dynamic messages on a user interface page is provided. A first software object may be built having a plurality of rows, and corresponding job request values being stored in a corresponding one of the plurality of rows. The first software object may be parsed and a dynamic message framed for each row of the first software object. A second software object may be build including a row for each of the framed dynamic messages and added to a session context being persistent across a first and second user interface pages. The second user interface page is displayed with a plurality of dynamic messages therein using a static message and a unique URL stored in each of the rows of the second software object.

1. Field of the Invention
The present invention relates to the field of computer-implemented messaging methods and systems. More particularly, the present invention relates to computer-implemented methods for displaying multiple dynamic messages on a user interface.
2. Description of the Prior Art and Related Information
When the user is called upon to initiate a function, confirm some action or otherwise interact with an application on a user interface (hereafter, UI), the application conventionally causes a message to be displayed on the UI. The application conventionally causes a message box to be displayed on the UI to display the message. Such a message box may be used to display a variety of user-related messages such as, for example, an error message, a confirmation message, a warning message or an informational message, to name but a few possibilities. Such messages, therefore, are often displayed as a result of the user carrying out some action on the web UI. For example, a user may be transferring $100 from one account to another account at his or her bank. In this example, a confirmation message may be generated in a message box, which message box may be rendered on the current web page or on another web page.
The message box may display a standard and static message such as, for example, "Your requested action has been performed and completed." Such a standard and static message may be utilized for many different user actions, but is not very informative or precise. Alternatively, the message box may display a dynamic message that is customized to the user's action that is the subject of the message. Such a custom and dynamic message may take the form of, for example, "$______ successfully transferred from account number ______ to account number ______. Your confirmation number for this transfer is ______", where the blanks are dynamically replaced with the pertinent information of the user's just completed transfer.
However, as it may be appreciated, some instances require more than one dynamic message to be displayed in a single message box. Such dynamic messages may be as simple as name/value pairs, optionally with HTML tags to control the appearance of the message. Conventionally, for such dynamic messages to be displayed, a corresponding plurality of message boxes must be generated and rendered, each displaying a single dynamic message. Such multiple message boxes each displaying a single dynamic message, whether displayed on the same or different UI pages, are cumbersome for the user and do not make efficient use of the UI real estate.
However, no mechanism is available that allows a single message box to display multiple different dynamic messages. For example, no available mechanism or method currently allows a single message box to display, in one step, a plurality of dynamic messages of the form, for example:                1. $______ transferred from bank account number ______ to bank account number ______;        2. $______ transferred from bank account number ______ to bank account number ______;        3. $______ transferred from bank account number ______ to bank account number ______, and        4. $______ transferred from bank account number ______ to bank account number ______.where each of the blanks is dynamically replaced with its corresponding unique data from the transaction.
From the foregoing, it may be appreciated that improved computer-implemented methods and systems for enabling VIs (such as JAVA web pages, for example) to display a plurality of dynamic and unique messages (say, n dynamic and unique messages) each with different values in a single message box are needed. Such computer-implemented methods and systems would find utility in any instance wherein it is needed to generate ill web pages to display multiple dynamic messages related to user-submitted jobs and/or requests.

Methods and systems for displaying multiple unique dynamic messages on a user interface


A case (100), a rotor (200) that is freely rotatably supported in the case (100), and stators (110) for rotating the rotor by magnetic force are provided. The stator (110) contains a core (111) mounted at the outside of the case (100), and a magnetic coil (112) wound around the core (111). An end face of the core (111) constituting a magnetic pole is formed of at least non-laminate ferromagnetic substance, and exposed to the inner surface of the case (100) so as to form a part of the inner wall of the case (100).

A vacuum motor is known as an actuator used for a driving source such as a vacuum pump, a turbo molecular pump or the like. The vacuum motor is equipped with a rotor and a stator comprising an electromagnet for rotationally driving the rotor. As well known, the electromagnet is formed by winding a magnetic coil around a core. A laminate steel plate is used as the core constituting the electromagnet. The laminate steel plate is constructed by adhesively attaching plural thin steel plates to one another with resin adhesive agent.
It is required for the vacuum motor to keep the inside of the case to a high-vacuum atmosphere. In the conventional vacuum motor, a rotor and a stator are disposed in the case (JP-A-10-288191), and also a laminate steep plate is used as the core of an electromagnet constituting the stator, so that it is difficult to keep a high vacuum atmosphere in the case due to an effect of gas discharged from resin adhesive agent sandwiched between laminate steels.
Furthermore, when the vacuum motor is required to be operated under high temperature, a large amount of gas is discharged from resin adhesive agent sandwiched between laminate steel plates, it is further difficult to form a high-vacuum atmosphere.
The present invention has been implemented in view of the foregoing situation, and has an object to provide an actuator that can form a high-vacuum atmosphere in a case and also hold sufficient durability under operation at high temperature.


A shielding member includes a shielding plate for covering a part of a heat exchanger, heat transfer tube engagement sections for engaging with heat transfer tubes of the heat exchanger, fin engagement portions for engaging with fins of the heat exchanger, a bypass preventing rib for preventing air from being directed to the part of the heat exchanger, and a mismounting preventing portion for preventing the shielding member from being mounted on a heat exchanger that does not require blocking of air flow. The heat exchanger in which the part covered with the shielding member has no heat exchanging function is manufactured with the same components as those of a heat exchanger on which the shielding member is not mounted and the whole of which has a heat exchanging function.

The present invention relates to a shielding member used for an indoor unit of an air conditioner and an indoor unit of an air conditioner using the shielding member.
Conventionally, in a plurality of indoor units of an air conditioner, which have different cooling/heating capacities, there has been proposed to use a single casing and provide heat exchangers having different sizes (e.g., see Patent Document 1: JP 7-42010 Y2). Thereby, the casing is shared among the indoor units having different cooling/heating capacities to reduce the number of components, thus reducing manufacturing cost.
However, in the conventional indoor units of the air conditioner, since it is required to manufacture heat exchangers with different sizes depending on their cooling/heating capacities, the number of components is still large and the manufacturing cost is relatively higher.
In the conventional indoor units of the air conditioner, since heat exchangers with different sizes depending on their cooling/heating capacities are used, for example, if outdoor units are exchanged for larger ones than the originals so as to increase their cooling/heating capacities, it is also required to exchange indoor units for larger ones, because it is not possible to increase their heat exchanging capacities with the original heat exchangers. That is, it is difficult to increase the cooling/heating capacities of the indoor units of the conventional air conditioner.

Shielding member and indoor unit of an air conditioner


The invention illustrates a caliper body (1) for a disc brake, suitable for being arranged astride of a disc (40) for a disc brake, said disc (40) defining a first braking surface (41) and a second braking surface (42) opposite the first braking surface (41); said caliper body (1) comprising a first half-caliper (2) and a second half-caliper (3), which are obtained by casting without machining and are suitable for being connected together at respective contact surfaces (4′, 4″) defining a joining plane (P) of the half-calipers; said first half-caliper (2) comprising a wheel-side elongated portion (5), extending in a tangential direction, which is suitable for facing an axially inner surface thereof towards the first braking surface (41), and at least one first projecting portion (11), projecting in an axial direction provided with a first contact surface (4′) suitable for connecting with the second half-caliper (3); said second half-caliper (3) comprising a vehicle-side elongated portion (6), extending in a tangential direction, which is suitable for facing an axially inner surface towards the second braking surface (42), an attachment portion (7) suitable for being connected to a support for the caliper and at least one second projecting portion (12), projecting in an axial direction provided with a second contact surface (4″) suitable for connecting with the first half-caliper (2); the first projecting portion (11) and the second projecting portion (12) being suitable for being connected together at the respective contact surfaces (4′, 4″) so as to form at least one bridge astride of the disc (40); each of said first projecting portion (11) and said second projecting portion (12) being provided with a radially inner surface (13′, 13″) suitable for facing the disc (40) that forms an angle α of between 90° and 92° with the respective contact surface (4′, 4″); in which the first projecting portion (11) extends farther in the axial direction with respect to the second projecting portion (12) so that said half-caliper joining plane (P) is axially closer to the vehicle-side elongated portion (6) with respect to the wheel-side elongated portion (5).

Generally, in disc brakes, the brake caliper is arranged astride of the outer peripheral edge of a brake disc. The brake caliper usually comprises a body having two elongated elements that are arranged so as to face opposite braking surfaces of a disc. Between each elongated element of the caliper and the braking surfaces of the brake disc there are friction pads. At least one of the elongated elements of the body of the caliper has cylinders suitable for receiving hydraulic pistons capable of exerting a thrusting action on the pads, abutting them against the braking surfaces of the disc to exert a braking action on the vehicle.
The brake calipers are usually fixedly connected to a support structure that remains fixed to the vehicle, like for example an axle-journal of a vehicle's suspension.
In a typical arrangement, one of the two elongated elements has two or more attachment portions of the body of the caliper to the support structure, for example providing slots or eyelets, for example arranged axially, or through holes, for example arranged radially, suitable for receiving screws for fixing the caliper that, with their ends are received in threaded holes provided on the support of the caliper.
In a typical construction of a caliper body, the elongated elements arranged facing the braking surfaces of the disc are connected together by bridge elements arranged astride of the disc.
A caliper body of this type is described in EP-A-2022999. FIG. 1 of EP-A-2022999 shows a caliper body of the fixed caliper type. This caliper body is of the monoblock type comprising two elongated elements the ends of which are connected together by bridges. Stiffening shafts extend between the elongated elements and between the two bridges forming a cross structure.
Typically, the body of the caliper is made from metal like for example aluminium, or aluminium alloy or cast iron. The body of the caliper can be obtained by casting, but also by chip-removal machining, as well as by forging.
The body of the caliper can be produced in a single piece or monoblock, but also in two half-calipers typically connected together along a plane that usually coincides with a middle plane of the disc on which the caliper is arranged astride.
In the case in which the driver of an automobile wishes to brake or slow down the movement of the vehicle, he applies a force on the brake pedal. Such a force on the brake pedal, through a brake pump, exerts a pressure on the brake fluid that, through a duct, is applied to the brake fluid present in the hydraulic circuit arranged inside the body of the caliper until the cylinders are reached where the pressure is exerted on the surface of the bottom of the pistons, forcing them to clamp against the pads that, in turn, abut against the braking surfaces of the disc.
The pressure action of the brake fluid also acts on the bottom wall of the cylinder causing a reaction in the caliper body that axially deforms it away from the surfaces of the disc. This deformation of the caliper body leads to an increase in the stroke of the pistons and therefore to an increase in the stroke of the brake pedal.
The body of the caliper also deforms as a function of the torque, exerted by the action of the pistons that abut the pads against the braking surfaces of the disc, which applies a deformation moment in directions that form torque arms with respect to the attachment points of the caliper body to its support. Such a torque deforms the caliper body also in a tangential and radial direction with respect to the disc.
Moreover, in cases in which the caliper body comprises two half-calipers, a high tension zone is created at the joining plane of the two half-calipers, which, as stated earlier, usually coincides with the middle plane of the disc on which the caliper is arranged astride.
At such a middle plane, both in monoblock caliper bodies and in caliper bodies comprising two half-calipers, there is a build-up of the tensions due to the aforementioned torque effects and the tensions generated by the pressure of the pads i.e. by the axial deformation. In the case of caliper bodies comprising two half-bodies, these tensions are added to by the tension caused by the screw tightening at the same plane. In other words, the screw that joins the two half-calipers generates a pulling tension at the joining plane of the two half-calipers that adds to the aforementioned tensions, creating a critical zone.
The caliper body must therefore have a sufficient structural rigidity, so as to ensure that the deformation of the caliper body caused by the braking action is kept within tolerable values, so as to avoid damaging the braking system and not to give the driver the feeling of having a non-responsive braking system, determining an extra stroke of the lever or pedal of the braking system and creating a feeling of a "spongy" system. This requirement pushes towards having extremely rigid structures for the caliper bodies and thus increasing their bulk and weight, especially in the most critical areas.
On the other hand, the caliper body, being fixedly connected to the vehicle's suspension and being arranged astride of the disc, is one of the non-suspended masses that it is wished to reduce as much as possible to increase the performance of the vehicle.
Such considerations are extremely important when the vehicle is a racing vehicle and the user wishes to have a braking system that is extremely responsive to his commands and at the same time is extremely light so as not to penalise the performance of the racing vehicle.
There is therefore a need for a caliper body for a disc brake that has improved structural characteristics for the same weight of the caliper body, or else one with the same structural characteristics that is lighter than the solutions of the prior art.
There are known solutions for caliper bodies specially studied to increase the characteristics of structural rigidity. For example, the aforementioned patent application EP-A-2022999, international patent application PCT/EP2005/050615 and American patent U.S. Pat. No. 3,183,999 all have solutions for caliper bodies equipped with reinforcement elements, for example arranged around the caliper bodies. In some of these known solutions the caliper body is of the symmetrical type according to planes passing through the axis of the disc or through the middle of the disc. In other solutions the caliper body has large and distributed windows, possibly passing right through, which form elongated reinforcement elements arranged longitudinally to the caliper body.
Although satisfactory from various points of view, these known solutions do not allow achieving structures that maximise the structural rigidity of the caliper body, reducing its weight and at the same time keeping the bulk as low as possible so as to facilitate the mounting of the caliper body also inside rims and wheels on which brake discs having a large diameter are mounted.


A denitrification reactor with a culture fixed to an organized plastic-type support is combined with an installation for the nitrification and elimination of the carbon-based pollution The reactor is supplied with a mixture of the raw effluent to be treated and of the effluent originating from the installation for the nitrification and elimination of the carbon-based pollution. The reactor includes two denitrification compartments (3, 4) arranged in parallel and operating altenatingly between a filling phase (denitrification and self cleaning-out of the excess biomass); and an emptying phase (denitrification and drainage of the excess biomass). A system for supplying the mixture of effluents consisting of a rotary arm (11) which alternately supplies the mixture to each of the compartments.

It is known that the treatment of nitrogen in waste-water is carried out in two steps:                a nitrification step during which the oxidation of the ammoniacal nitrogen, present in the effluent, to nitrite and then to nitrate is carried out by means of a biochemical reaction due to the action of autotrophic bacteria, and        a denitrification step during which the nitrate nitrogen is reduced to a lower oxidation state by means of a biochemical reaction using heterotrophic bacteria.
Each of these two steps requires a certain number of conditions to be observed:                the nitrification step requires: a high sludge age, since the autotrophic biomass has a slow growth rate; a pH of between 6 and 8 with an optimal value of the order of 7, given that the growth rate of nitrifying bacteria decreases outside these pH values, and a dissolved oxygen content maintained at between 2 and 4 mg/l;        the denitrification step requires the following constraints to be observed: a low sludge age, given that the heterotrophic biomass exhibits rapid growth; a pH of between 6 and 8, with an optimal value of the order of 7; a very low dissolved oxygen content (anoxic conditions), given that the presence of oxygen inhibits denitrification, and a BOD5 sufficient to satisfy the organic carbon needs.
It results from these constraints that the nitrification and denitrifications phenomena are entirely contradictory. It is the reason for which constructors of wastewater treatment plants have based their technique on spatial and/or temporal alternation of the aeration (nitrification) and anoxic (denitrification) phases.
It is known, moreover, that the denitrification rate depends on two essential parameters: firstly, the temperature, and secondly, the organic carbon available in the biological sludge, and therefore on the amounts of organic carbon provided by the effluent to be treated (at 15° C., the values are close to 2.5. to 3 g N—NO3/kg VSS/h).
At the current time, the denitrification process can be carried out in three different ways:                in an anoxia zone in free culture. The anoxic tank is located at the head of the treatment system and it is responsible for the denitrification. The supply of NO3− is provided by recirculation of the mixed liquor originating from the aeration tank, and the organic carbon needs are satisfied by the inlet of pretreated water. The denitrifying biomass is recirculated from the clarifier to the anoxic tank. The aeration tank ensures the nitrification and the additional elimination of the carbon-based pollution. The drawback of this configuration comes from the fact that it requires a recirculation of the order of 150 to 400% of the raw water flow in order to recycle the nitrates to be eliminated and so as to observe a sufficient C/N ratio. In general, the volume of the anoxic tank represents 25% of the total volume required for purification;        in the aeration-syncopating aeration tank, temporal alternation allows nitrification-denitrification in a single tank. In this case, the following optimum conditions should be observed: a sludge age of more than 10 days; a 30% increase in the aeration compared with the requirements of only elimination of the carbon-based pollution; a minimum anoxia time of the order of 8 to 10 h/day, and a sludge content of approximately 4 g VSS/l;        in a fixed-biomass installation (biofilter) which, in the same way as an anoxia zone, can make it possible to provide denitrification on the condition that air is injected in order to guarantee a homogeneous and controlled detachment of the excess biomass.

Denitrification reactor with a fixed culture


In a data communication system such as a high capacity DBS system, dynamic mapping of broadcast resources is provided to exploit occasional redundancy in the program content of two or more input data streams, freeing at least one broadcast resource to carry alternate bitstreams, such as additional programs or existing programs at higher quality. Transmission maps defining the correspondence between input data streams and broadcast resources, and reception maps defining the correspondence between broadcast resources and output data streams, are updated as needed to dynamically modify broadcast resource mapping to increase effective utilization of available bandwidth. Beneficial n:n-y:m mapping in a high capacity consumer DBS entertainment system is provided. Apparatus and methods for efficiently generating, maintaining and updating allocation maps with reduced overhead requirements, are disclosed.

The present invention relates in general to the processing of high data rate information signals. In particular embodiments it relates to processing of video, audio and/or data information in a direct broadcast satellite (DBS) consumer entertainment system.
The information carrying capacity of any data network is limited by, among other things, its effective bandwidth. Limitations in available bandwidth, resulting from technical limitations of the processing and transmission elements (e.g. transmission line limitations), from government limitations (e.g. limited RF spectrum allocation), or otherwise, restrict the amount of information which can be carried by the related system. This may result in a limitation on the quantity or quality (or both) of the services which may be provided by the system, often requiring compromises or tradeoffs.
Transmission of television programming to home viewers has long been subject to the these limitations and tradeoffs. Terrestrial RF broadcasts are limited in a given locality to a few frequency bands (channels) allocated by government authority for television transmission, and selected to be noninterfering over the limited range of the transmission. The frequency band allocated to each channel was selected to accommodate the then-standard transmission scheme employed (e.g. NTSC in the United States), and to minimize or avoid out-of-band interference. Although additional frequencies (e.g. UHF in the United States) were later allocated, restrictions on available RF spectrum have long limited the number of programs which could be made available to the consumer.
Distribution of program material via cable networks provided additional bandwidth to broadcasters (i.e. cable operators), overcoming in part the restriction imposed by scarcity of available RF spectrum. However, cable systems are technically limited to the useable bandwidth of the network, including the transmission line and associated electronics.
Advances in signal processing technology have permitted more programming information, improved quality, and new services (e.g. data services) to be transmitted within a given available bandwidth. For example, digital processing of both video and audio signals, together with advances in encoding and compression techniques (e.g. MPEG and MPEG-2), have permitted a reduction in the bandwidth required for transmission of video and audio signals of acceptable quality, and/or transmission of higher quality video and audio signals. Together with advances in the associated transmission and reception equipment allowing greater utilization of available spectrum, a dramatic increase in the amount of user programming that can be transmitted over a given medium is possible. In addition, systems have been developed to utilize alternative delivery systems and other portions of the RF spectrum. For example, direct broadcast satellite (DBS) systems provide entertainment and information broadcasts directly to consumers, in some cases by means of high power satellite transponders and small (e.g. 18-inch) consumer receiving dishes. Although one such system is today capable of transmitting over 175 channels of video, audio and/or data programming at higher quality levels than previously known, there remains a desire to provide additional transmission capability and to fully utilize all available bandwidth for benefit of the consumer.
Distribution systems, whether broadcast (satellite or terrestrial), cable, optical, or otherwise, typically provide a plurality of accessible broadcast resources. In an early model, a terrestrial television broadcast system included a number of individual channels or frequency bands, selectable by the consumer. Taking the television system as a whole, each channel available in a given locality provided a broadcast resource accessible by the users in that region and capable of carrying a single video/audio program. Similar frequency division multiplexing on known analog cable systems provides a generally larger number of broadcast resources in the system, again each typically carrying a single program including both video and audio, selectable as a viewer channel. In a digital DBS system, frequency and phase division multiplexing (e.g. multiple transponders operating within assigned frequencies and with LHCP and RHCP polarization) and time division multiplexing (e.g. TDM within a given frequency) may be used. In this context, each individually addressable bitstream (i.e. each selectable time slot on each selectable frequency and phase) may be considered as a separate "broadcast resource." Where different satellite locations or different delivery media are also employed in an extended system, selection of the desired satellite and transmission media, etc., is also part of identifying an individual broadcast resource.
A broadcast service will therefore have available to it a limited number of broadcast resources. If the quality of individual transmissions can be acceptably reduced, additional broadcast resources might be supported within a given RF spectrum allocation. However, the number of broadcast resources available for transmitting high quality video, audio and data programming remains limited.
A broadcaster or service provider desires to transmit to its customers (e.g. subscribers) the maximum number of programs possible utilizing the available transmission system, at the highest relative quality. As used herein, "programs" shall include video programming, audio programs, and/or data transmission of various types (e.g. software, control codes, multimedia content, digitized pictures, data, etc.). A program may include more than one form of data, such as video and one or more audio, and in some embodiments, associated data. Each of these data streams may, in preferred embodiments, be transmitted over separate broadcast resources.
A large number of content providers exist today and make available to broadcasters one or more content streams comprising programs and related content (e.g. program IDs, commercials, etc.). Many of these streams are continuous or substantially continuous, and are distributed by the content provider through various distribution media (e.g. satellite, cable, or prerecorded media) to, among other potential recipients, other broadcast services for retransmission to their viewers. For example, numerous regional sports networks exist which assemble program streams containing sporting events, often with sports-related "filler" in the times between individual sporting events.
Although content providers often generate original programs (e.g. by covering a live sporting event), it is common in the industry for one content provider to purchase programs or filler from another content provider. For example, a sports network might purchase retransmission rights to a sporting event being covered by another service provider. In these cases, the purchasing provider receives a program feed from the distribution medium (e.g. satellite) utilized by the originating provider, then retransmits this signal to its customers (e.g. cable system operators for further retransmission to consumers, or directly to consumers). The purchasing provider may insert its own commercials or identity, or may elect to use the purchased feed in its "raw" form. Often several service providers will purchase and carry the same programming originated by another provider.
A multi-channel broadcast system will typically purchase a number of input program streams from a number of content providers, for retransmission to viewers or subscribers of that system. In a digital transmission system, each individual program stream can be viewed as a continuous input data stream, where the data represents video, audio, or other (e.g. multimedia or data) information, and will be referred to herein as an "input data stream." A given program may comprise one or more than one input data streams (e.g. one or more video inputs, one or more associated audio inputs, and associated data relating to the program content). Transmitting a given number of input data streams to a number of viewers, such that each data stream is potentially available to users at all times, has typically required at least an equal number of broadcast resources.
In particular, at the transmission end each input data stream is typically assigned to an available broadcast resource. Each input data stream is therefore allocated or "mapped" to a unique broadcast resource. The correspondence matrix identifying the input stream-to-broadcast resource relationships may be considered as a "map". Because the map used at the transmission end is remote from the user (e.g. subscriber), it will be referred to herein as a "remote" map.
At the receiving end, a similar map has been used to allocate the data streams received from the broadcast resources to unique, selectable outputs. Each individual output bitstream, corresponding to a particular broadcast resource bitstream, may be referred to as an "output data stream." When a user selects a particular channel (e.g. channel 101) they expect to receive a particular program at a particular time. The receiving device accomplishes this by maintaining a complimentary receiver or "local" map which specifies the correspondence between broadcast resources and selectable outputs. In some instances, where the desired output consists of information carried over just one broadcast resource, the local map will specify correspondence between that broadcast resource and the selected output, which will consist of a single output data stream. For example, if the video and audio components of a program are encoded into a single input data stream, then selection of a program or viewer channel requires mapping of only one data stream, with the components being separated by other processors. In other instances (e.g. a movie having one or more video options, a plurality of selectable high quality audio, and/or optional related data), selection of a desired output may require mapping multiple output data streams to the corresponding broadcast resources. In these instances, the user selects a desired "viewer channel" (e.g. channel 101) and makes any optional selections (e.g. alternate audio), and the local map identifies the necessary output data streams and maps them to appropriate broadcast resources. These output data streams may be directed to an appropriate processing or performance device, such as (without limitation) a television display, audio processor, or computer. Where options are available (e.g. alternate audio), the selected option may be mapped to an output corresponding to a related processor based on a user select input, or all of the options may be mapped to a processor which itself isolates the appropriate output. In specific embodiments, components of different programs (e.g. video from a first program and audio from a different source) may be locally mapped to an output viewer channel, thereby creating a hybrid derived output.
It is important that both the remote and local maps correspond at any given time, so that selection by the user of a viewer channel will map the receiving circuitry to the correct broadcast resource(s) which, in turn, are mapped to the input data stream(s) desired by the user. It is known to modify the allocation maps from time to time. This may be done, for example, when a broadcast resource becomes unavailable, or when a reallocation of bandwidth provided by individual resources is required, such as when new input data streams are added to, or old ones removed from, a system. Such map changes have been infrequent, however, typically one to three times per day.
It is also known to locally generate derivative output data streams or viewer channels which do not correspond to any single input data stream. For example, a local processor may map a particular viewer channel to a first set of one or more broadcast resources during a first time period, then map that viewer channel to a different set of broadcast resources during a subsequent time period. In this manner, a processor has been able to provide viewers with a greater number of viewer channels than the number actually broadcast.
For purposes of the ensuing description and claims, the following notation convention may be useful. The numerical correspondence between individual input data streams and individual broadcast resources (related to the remote map), and the numerical correspondence between those broadcast resources and individual output data streams (related to the local map), may be given as IN:BR:OUT, where IN equals the number of discrete input data streams, BR represents the number of discrete broadcast resources, and OUT represents the number of discrete output data streams. In the simplest 1:1:1 correspondence, n input data streams are mapped to n broadcast resources, which are in turn mapped to n output data streams, or n:n:n. As previously noted, it is also known to generate derivative channels, which may be represented as n:n:n+x correspondence or mapping, where n and x are integers greater than or equal to one. In this example, although a 1:1 correspondence exists between input data streams and broadcast resources, a 1:>1 mapping is performed by the local map, resulting in x derivative output channels.
Although revision of the maps to accommodate infrequent changes in the input data streams or active broadcast resources, and n:n:n+x mapping to locally generate derivative channels, have provided a useful degree of flexibility in the operation of existing systems (e.g. high capacity DBS), it would be useful to reduce the amount of bandwidth required to carry desired programming, thereby allowing additional services and/or higher quality services to be carried by the same broadcast resources.
Finally, it is known that certain control and configuration information must be transmitted, in addition to the desired input data streams. Using channel maps introduces difficulties in generating and maintaining an accurate local map which reflects the current utilization of broadcast resources. Changes in the utilization of resources over time require the local map to be updated, typically by transmitting or downloading a new map to a viewer's receiver such as (for a typical DBS system) an integrated receiver/decoder (IRD). For a system having a large number of channels (i.e. 175 or more), the local map may comprise a matrix of several thousand bytes of data listing the appropriate broadcast resources for each viewer channel, for one or more time periods. Such "overhead" data transmission requires bandwidth which is therefore not available for delivery of desired consumer services. In the case of infrequent map updates, this overhead has been tolerable, although not desired. If the complexity or size of the local map were increased, or if revisions to the local map were frequent, the amount of overhead bandwidth required could become unacceptably large.
Transmission of local map data also requires time, the amount of which depends on the amount of map data and the allocated effective baud rate. Other sources of delay in generating and activating an updated map may also exist. For example, an IRD ordinarily continues to use a map until it determines the complete transmission of a more recent, updated map. Typically the IRD checks for the existence of an updated map at only predetermined intervals. Thus, another source of delay is introduced in activating a new local map.
The time delays involved with transmitting updated local maps to IRDs have also made maintaining updated maps cumbersome. The transmission of updated maps has thus been typically limited to a fixed number of predetermined times during the broadcast day, e.g. two or three times per day. Changes in the utilization of broadcast resources are therefore limited by the practical ability to update the local map. Improved flexibility in updating channel maps would allow greater flexibility in maximizing the utilization of broadcast resources.


Compounds of formula I

This invention relates to derivatives of 5,5-disubstituted pyrimidine-2,4,6-triones. These compounds show a marked antitumor and antimetastatic activity.
In normal tissue there is an equilibrium between synthesis and degradation. Extracellular matrix is degraded by proteinases which belong to at least three groups of matrix metalloproteinases. These are the collagenases, gelatinases and stromelysins. Normally there are specific inhibitors for these catabolic enzymes such as xcex12 macroglobulines and TIMP (=tissue inhibitor of metalloproteinases (MMP)) so that an excessive degradation of extracellular matrix does not occur. Adamalysins are a related group of proteinases. A prominent member of the adamalysins is TACE (TNF-xcex1-converting enzyme).
At least 17 different and yet highly homologous MMP species have been characterized, including the interstitial fibroblast collagenase (MMP-1, HFC), the neutrophil collagenase (MMP-8, HNC), two gelatinases, stromelysins (such as HSL-1) and HPUMP (for a recent review, see Birkedal-Hansen, H., Moore, W. G. I., Bodden, M. K., Windsor, L. J., Birkedal-Hansen; B., DeCarlo, A., Engler, J. A., Critical Rev. Oral Biol.Med. (1993) 4, 197-250. These proteinases share a number of structural and functional features but differ somewhat in their substrate specificity. Only HNC and HFC are capable of cleaving type I, II and III native triple-helical collagens at a single bond with the production of fragments xc2xe and xc2xc of the native chain length. This lowers the collagen melting point and makes them accessible to further attack by other matrix degrading enzymes.
However, the uncontrolled excessive degradation of this matrix is a characteristic of many pathological states such as e.g. in the clinical picture of rheumatoid arthritis, osteoarthritis and multiple sclerosis, in the formation of tumor metastases, corneal ulceration, inflammatory diseases and invasion and in diseases of bone and teeth.
It can be assumed that the pathogenesis of these clinical pictures can be favourably influenced by the administration of matrix metalloproteinase inhibitors. In the meantime a number of compounds are known from the literature (see e.g. the review article of D. E. Levy, A. M. Ezrin Emerging Drugs 2,205-230 (1997), M. Whittaker, P. Brown, Curr. Opin. Drug Discovery Dev. (1998), 1(2), 157-164. or are described in the patent literature, mainly with a hydroxamic acid residue, a thiol or phosphine group as a zinc binding group (see e.g. WO-A-9209563 by Glycomed, EP-A-497 192 by Hoffmann-LaRoche, WO-A-9005719 by British Biotechnology, EP-A-489 577 by Celltech, EP-A-320 118 by Beecham, U.S. Pat. No. 459 5700 by Searle, WO 97/20824 by Agouron Pharmaceuticals, WO 96/15096 by Bayer Corporation among others).
Some of these compounds show a high activity as inhibitors of matrix metalloproteinases but their oral availability is very low. Also such compounds often show broad spectrum inhibition of metalloproteinases which may be associated to undesired side-effects and toxicity.
Pyrimidine-2,4,6-trione derivatives have been described in EP0869947 generically as inhibitors of matrix metalloproteinases. However, there is still a high need for new compounds having low toxicity, no side-effects and a marked inhibitory activity against metallo-proteinases, especially as candidates for a chronic treatment against tumor growth and metastasis.
It has now been found that the claimed pyrimidine-2,4,6-trione derivatives have improved activity as matrix metallo-proteinase inhibitors over the compounds claimed in EP0869947 and also show good oral availability.
The present invention concerns compounds of the formula I
in which
R1 represents a phenyl, phenoxy , phenylthio, phenylsulfmyl, phenylsulfonyl , phenylamino or phenylmethyl residue, wherein the phenyl moiety is unsubstituted or substituted by one or more halogen atoms, hydroxy, C1-C6 alkoxy, C1-C6 alkyl cyano, or nitro groups, and R2 represents an unsubstituted or substituted aryl or hetaryl group.
When the phenyl moiety of R1 is a substituted phenyl moiety, it is preferred that there are one or two substituents in the para and/or meta positions.
The present invention also encompasses pharmaceutically acceptable salts or prodrugs of the compounds of formula I as well as the use of these compounds to produce pharmaceutical agents.
It has now been found that the pyrimidine-2,4,6-trione derivatives of the present invention, have improved activity as matrix metallo-proteinase inhibitors over the compounds claimed in EP0869947 and also show good oral availability.
The aryl group of R2 consists of a phenyl ring. The hetaryl group is a cyclic unsaturated or saturated ring system consisting of 5 to 7 ring atoms which can be selected from one or more carbon, nitrogen, oxygen or sulfur atoms. Preferred are electron deficient hetaryl residues such as the nitrogen containing 6 membered rings like pyridines, pyrimidines, pyrazines or 1,3,5-triazines or its N-oxides. Most preferred are the hetaryl residues pyrimidinyl or pyrazinyl.
The aryl or hetaryl rings may be substituted by one or more substituents selected from halogen, hydroxy, alkoxy, amino, dialkylamino, cyano, lower alkyl, lower alkenyl, lower alkinyl, lower acyl, lower alkylthio, lower alkylsulfonyl, lower alkylaminocarbonyl, aminocarbonyl, SO2NR3R4, nitro, lower alkoxycarbonyl, carboxy, wherein R3 and R4, which can be the same or different represent hydrogen; C1-C6 alkyl, straight chained or branched, which can be substituted one or several times by OH, N(CH3)2 or which can be interrupted by oxygen, or represent CO R5, wherein R5 is an alkyl group which can be substituted by NH2. Preferred are substitutions in para and/or meta position by one to two of the above listed substituents.
Lower alkyl in residue R2 as such or in combinations with other residues denotes C1-C6-alkyl, preferred are methyl, ethyl, propyl, isopropyl or tert.-butyl.
Lower alkenyl denotes C2-C6 alkenyl, preferably allyl or pentadienyl. Lower alkinyl denotes C2-C6 alkinyl, preferably propargyl.
Lower acyl in the residue R2 above all denotes xe2x80x94C(O)xe2x80x94C1-C6-alkyl or xe2x80x94C(O)H, preferred for an acetyl group.
The alkyl residues in R2, can optionally be interrupted once or several times by heteroatoms (O, S, NH).
Halogen is understood as fluorine, chlorine, bromine, iodine, preferably chlorine or bromine.
If compounds of the formula I contain one or several asymmetric carbon atoms, the optically active compounds of the formula I are also a subject matter of the present invention.
Compounds of the formula I can be synthesized by well-known processes preferably in that compounds of the formula II
in which R1 has the above-mentioned meaning and T represents a leaving group such as Hal or OSO2R3 Hal denoting chlorine, bromine or iodine and R3, denoting an aryl or a methyl residue, are reacted with a compound of the formula III
in which R2 has the meaning stated above and optionally converted into pharmaceutically acceptable salts.
Compounds of the formula II can be synthesized by analogy to known literature procedures. Thus for example pyrimidine-2,4,6-triones brominated in the 5-position can be synthesized by reacting the appropriate bromomalonic acid dialkyl esters with urea (e.g. Acta Chim. Acad. Sci. Hung. 107 (2), 139 (1981)). The corresponding brominated or chlorinated compounds of the formula II can be obtained by reacting pyrimidine-2,4,6-triones substituted by R1-Phenyl in the 5-position with bromine (analogous to J. Prakt. Chemie 136, 329 (1933) or J. Chem. Soc. 1931, 1870) or sulfuryl chloride (J. Chem. Soc. 1938, 1622) or N-bromo-succinimide or similar brominating agents. Such procedures are also described in EP0869947.
Amines of the formula III are commercially available or are usually known in the literature or in analogy to the described methods in the experimental part.
Pyrimidine-2,4,6-triones of formula II with T representing hydrogen can be prepared according to known methods by reacting malonic acid esters with urea (see for example J. Med. Chem. 10, 1078 (1967) or Helvetica Chim. Acta 34, 459 (1959), Pharmacie 38 (1), 65 (1983)) or EP0869947. The reactions are usually carried out in alcohols such as methanol, ethanol or butanol in the presence of an appropriate sodium alcoholate at temperatures between 40xc2x0 C. and 100xc2x0 C.
The malonic acid esters which are needed for the preparation of pyrimidine-2,4,6-triones are known from the literature or can be produced according to processes known from the literature. A convenient process for the preparation of malonic acids where R1 has the above mentioned meaning is described in the following scheme:
Examples for these reactions can be found in Houben-Weyl Vol E5/2, J. Org. Chem. 46, 2999 (1981) and Arch. Pharm. 323, 579 (1990).
Compounds of the formula I can contain one or several chiral centres and can then be present in a racemic or in an optically active form. The racemates can be separated according to known methods into the enantiomers. Preferably diastereomeric salts which can be separated by crystallization are formed from the racemic mixtures by reaction with an optically active acid such as e.g. D- or L-tartaric acid, mandelic acid, malic acid, lactic acid or camphorsulfonic acid or with an optically active amine such as e.g. D- or L-xcex1-phenyl-ethylamine, ephedrine, quinidine or cinchonidine.
Alkaline salts, earth alkaline salts like Ca or Mg salts, ammonium salts, acetates or hydrochlorides are mainly used as pharmaceutically acceptable salts which are produced in the usual manner e.g. by titrating the compounds with inorganic or organic bases or inorganic acids such as e.g. sodium hydroxide, potassium hydroxide, aqueous ammonia, C1-C4-alkyl-amines such as e.g. triethylamine or hydrochloric acid. The salts are usually purified by reprecipitation from water/acetone.
The compounds of formula I and salts thereof according to the invention can be administered enterally or parenterally in a liquid or solid form. In this connection all the usual forms of administration come into consideration such as for example tablets, capsules, coated tablets, syrups, solutions, suspension etc. Water which contains additives such as stabilizers, solubilizers and buffers that are usual in injection solutions is preferably used as the injection medium.
Such additives are e.g. tartrate and citrate buffer, ethanol, complexing agents (such a ethylenediaminetetra-acetic acid and non-toxic salts thereof), high-molecular polymers (such as liquid polyethylene oxide) to regulate viscosity. Liquid carrier substances for injection solutions have to be sterile and are preferably dispensed into ampoules. Solid carrier substances are e.g. starch, lactose, mannitol, methylcellulose, talcum, highly dispersed silicic acids, higher molecular fatty acids (such as stearic acid), gelatins, agar-agar, calcium phosphate, magnesium stearate, animal and vegetable fats, solid high-molecular polymers (such as polyethylene glycols); suitable preparations for oral application can optionally also contain flavourings and sweeteners.
The dosage depends on various factors such as manner of administration, species, age and/or individual state of health. The doses to be administered daily are about 10-1000 mg/human, preferably 100-500 mg/human and can be taken singly or distributed over several administrations.
Prodrugs of the compounds of the invention are such which are converted in vivo to the pharmacological active compound. The most common prodrugs are carboxylic acid esters.

Pyrimidine-2,4,6-trione derivatives, processes for their production and pharmaceutical agents containing these compounds

Abstract: Compounds of formula I

Abstract: in which

Abstract: R1 represents a substituted or unsubstituted phenoxy, phenylthio, phenylsulfinyl, phenylsulfonyl, phenylamino or phenylmethyl residue, and

Abstract: R2 represents an optionally substituted aryl or heteroaryl residue, with metallo-proteinase inhibitor activity.


An adjustable seat back assembly for a wheelchair of the type having a frame with an upwardly extending rear frame portion and an adjustable angle seat support which includes a pivotable front end and a rear end which is secured to said rear frame portion at any of a plurality of different positions. A seat back support is mounted to pivot on the seat support from adjacent its rear end. A link connects the seat support to a slider on the rear frame portion to maintain the position of the slider relative to the seat back support pivot as the seat angle is adjusted. A releasable seat back angle adjuster secures the seat back support to the slider at any of a plurality of positions. When the seat back angle adjuster is released, the seat back support may be folded down towards said seat support.

Adjustable wheelchairs are frequently used by persons requiring wheelchairs who are involved in action sports such as basketball, tennis and other sports. As taught, for example, in U.S. Pat. No. 5,509,893, various settings of a wheelchair may be made adjustable, including the wheel location relative to the center of gravity, the wheel camber, and the seat angle.
The seat, for example, may be mounted to top rails or supports on side frames for the wheelchair. The top rail on each side frame is pivoted from near the front of the frame over an arc on a back frame member for seat angle adjustment. Quick release pins may be provided to secure the top rails to the back frame member at any of a plurality of discrete locations to provide a number of discrete seat angles. The lower end of seat back supports are hinged to each top rail. The back supports also are each connected to a slider which slides on the back frame member as the seat angle is adjusted. Consequently, the seat back moves up and down with the back of the seat as the seat angle is adjusted. The seat back angle will remain substantially constant as the seat angle is adjusted. There has been no provision for easily changing the angle of the seat back to accommodate the needs of a user or to permit the seat back supports to be easily folded down for storage or transport without the use of tools.

Adjustable seat back assembly for a wheelchair


The present invention provides a coil spring, in which a corresponding portion is provided at an end portion in a direction of a coil axis, the corresponding portion having a whole size in the direction of the coil axis of the plurality of wire materials adjacent to each other in the direction of the coil axis equal to a maximum value of a gap in the direction of the coil axis between wire materials adjacent to each other in the direction of the coil axis of the coil spring, a gap in the direction of the coil axis between the corresponding portion and a wire material adjacent to the corresponding portion on an inner side in the direction of the coil axis is smaller than a wire height in an active coil portion of the coil spring, and at the end portion of the direction of the coil axis, a gap in the direction of the coil axis between a portion extending around the coil axis from the corresponding portion to a distal end portion side of the wire material and a wire material adjacent to the portion on the inner side in the direction of the coil axis gradually decreases from the corresponding portion toward the distal end portion side of the wire material around the coil axis.

In related art, a coil spring formed by winding a wire member around a coil axis has been widely used.
In this type of coil spring, when a plurality of coil springs are accommodated together at random, the coil springs become entangled with each other, and for example, there is a possibility of reduction in production efficiency.
In the coil spring shown in the following Patent Document 1, a plurality of densely winding portions formed by abutting or approaching wire members in a direction of the coil axis are provided. This prevents the densely winding portion from entering a gap (hereinafter referred to as a wire member gap) in the direction of the coil axis between the wire members adjacent to each other in the direction of the coil axis of another coil spring.


A sialon composite and fabrication method thereof in which the phase of a surface layer thereof is modified differently from that of the bulk. The surface layer is modified to .alpha.-sialon or .alpha.-.beta. sialon composite but the bulk is .beta.-sialon. Also, the surface layer is modified to .beta.-sialon or .alpha.-.beta. sialon composite but the bulk is .alpha.-sialon.

1. Field of the Invention
The present invention relates to the surface modification of sialon ceramics and surface modified sialon ceramics prepared thereby, wherein the phase of the surface layer in sialon ceramics has the different phase from the bulk phases.
2. Description of Prior Art
Si.sub.3 N.sub.4 has two different structural modifications, .alpha. and .beta.. The solid solution in .beta.-Si.sub.3 N.sub.4, formed by simultaneous equivalent substitution of Al--O for Si--N called .beta.-sialon and the solid solution in .alpha.-Si.sub.3 N.sub.4 called a-sialon.
The general mechanical and thermal properties of sialon ceramics are summarized at Table. 1.
TABLE 1 ______________________________________ The General property comparison of .alpha.- and .beta.-sialon ceramics Properties .alpha.-sialon .beta.-sialon ______________________________________ Hardness (Hv, kg/mm.sup.2) .about.2000 .about.1500 Strength (MPa) 500.about.900400 Fracture Toughness (MPam.sup.1/2 ) 3.about.5 4.about.10 Thermal Oxidation Resistance good ______________________________________
The general formula of .beta.-sialon is, Si.sub.6-z Al.sub.z O.sub.z N.sub.8-z where z varies 0 to 4.2 within solubility range.
The general formula of .alpha.-sialon is M.sub.p Si.sub.12-(m+n) A.sub.(m+n) O.sub.n N.sub.16-n, where p, m and n are variable numbers. M denotes metal ion where, Li, Mg, Ca, Y, Er, Nd, Gd, Dy, Na, Ce, Sm, and Be. In a case of M=Y, Y-.alpha.-sialon(yttrium stabilized alpha sialon), m value varies 1.0 to 2.4 and n varies zero to 1.7 in relation to p-m/3.
In order to fabricate sialon ceramics, additives are usually used such as AlN, Al.sub.2 O.sub.3, Y.sub.2 O.sub.3, MgO, CaO, Li.sub.2 O.sub.3, Sm.sub.2 O.sub.3, Er.sub.2 O.sub.3, Yb.sub.2 O.sub.3, Dy.sub.2 O.sub.3, Gd.sub.2 O.sub.3, wherein positive metal ion penetrate into a network structure of Si.sub.3 N.sub.4 for forming .alpha.-sialon.
Sialon ceramics can be obtained from the powder mixtures of AlN, Al.sub.2 O.sub.3, Y.sub.2 O.sub.3, Si.sub.3 N.sub.4, and the amounts of each powder determine the phase ratio of the .alpha.- and .beta.-phase.
In general, the microstructure of .alpha.-sialon ceramics shows the equiaxed grains with high hardness, better wear and oxidation resistance, while .beta.-sialon ceramics by their elongated grains with better flexural strength and fracture toughness. To combine advantages in physical properties of both sialons, .beta.-.beta. sialon composite has long been studied. For example, comparing with pure .beta.-sialon, .alpha.-.beta. sialon composite shows improved hardness and oxidation resistance with reduction of flexural strength and fracture toughness. These properties vary almost linearly with the formation of added sialon.
The surface modification is another technique to improve the properties of ceramics. The surface modification provides opportunities of introducing surface compressive stresses which result from the difference in thermal expansion coefficient between a surface layer and bulk. Some previous results showed that the surface nitridation of dense SiC could improve surface-sensitive mechanical properties because of the thermally induced compressive stresses at the surface of sialon ceramics.

Method of producing a surface modified sialon composite


Mobile station equipment for a mobile communication system includes a decision section for deciding accuracy of data of a first signal transmitted from a base station, and a first signal strength measuring section for measuring a signal strength of the first signal. The mobile station equipment further includes an inquiring section for transmitting a permission request signal for a stand-by state process to the base station according to at least one of the decided accuracy and a comparison result of the measured signal strength of the first signal and a first given threshold value. And, in the mobile station equipment, a stand-by control section waits for permissible information to be transmitted from the base station equipment based on the permission request signal, and starts a stand-by state process upon receiving the permissible information.

1. Field of the Invention
The present invention generally relates to mobile station equipment, base station equipment, and a control method, and more particularly, to mobile station equipment, base station equipment, and a control method which are used to set a stand-by state of the mobile station in mobile communication systems.
2. Description of the Prior Art
In a mobile communication system such as a digital automobile telephone system, a variety of types of mobile station equipment such as a portable type, an on-vehicle type, and a portable on-vehicle-mountable type are used. In general, according to the type of the mobile station equipment, antenna configurations and transmission powers of the equipment are different. The portable and on-vehicle-mountable types of mobile station equipment may be moved to narrow spaces and into buildings to where the on-vehicle type of mobile station equipment cannot be moved. In this case, for the portable and on-vehicle-mountable types of mobile station equipment, a radio transmission path between a mobile station and a base station has a large transmission loss. And, a large multipath fading is caused by surrounding buildings and mountains, etc. As a result, a good transmission performance may not be necessarily obtained.
FIG. 1 shows a block diagram of a configuration example of conventional base station equipment. In FIG. 1, a transmit antenna 51 and a receive antenna 52 are respectively connected to corresponding antenna terminals of amplifier equipment 53. Ports of the amplifier equipment 53 are connected with transmitter/receiver shelves 55-1 to 55-3 through divider/combiner parts 54-1 to 54-3. Control inputs and outputs of the transmitter/receiver shelves 55-1 to 55-3 are connected to corresponding inputs and outputs of base-station control equipment 56. PCM-input-and-output terminals of the transmitter/receiver shelves 55-1 to 55-3 are connected to a PCM interface part 57. Further, the PCM interface part 57 is connected to synchronous terminal equipment 58 which is connected to a control center (not shown) through a transmission line.
The transmitter/receiver shelf 55-1 comprises transmitting-and-receiving parts 59-11 to 59-1N (N is a given number) which respectively correspond to a plurality of radio channels, and a shelf control part 60-1 generally controlling these transmitting-and-receiving parts 59-11 to 59-1N. The transmitter/receiver shelves 55-2, 55-3 also have the same configuration as that of the transmitter/receiver shelf 55-1.
FIG. 2 shows a block diagram of a configuration example of conventional mobile station equipment. In FIG. 2, an antenna 71-1 is connected to an antenna terminal of a transmit/receive duplexer 72, and a received signal from the antenna 71-1 is supplied to one input of a demodulator 74 through a receiving part 73-1. A received signal from an antenna 71-2 is supplied to the other input of the demodulator 74 through a receiving part 73-2. An output of the demodulator 74 is supplied to a TDMA part 75. The received signal passed through the TDMA part 75 is supplied to a codec (coder and decoder) 76 to be decoded. A decoded signal from the codec 76 is supplied to a speaker 77.
On the other hand, an output signal from a microphone 78 which forms a handset with the speaker 77 is supplied to the codec 76 to be coded. Coded signal from the codec 76 is supplied to a waveform-shaping part 79 through the TDMA part 75. A waveform-shaped signal from the waveform-shaping part 79 is supplied to a quadrature modulator 80, and modulates a carrier from a frequency synthesizer 82. The modulated carrier is supplied to a power amplifier 81, and is transmitted through the transmit/receive duplexer 72 and the antenna 71-1. Amplitude information of the waveform-shaped signal of the waveform-shaping part 79 is provided to the power amplifier 81 to control its operational point and increase its power efficiency. A receive local signal from the frequency synthesizer 82 is supplied to the receiving parts 73-1, 73-2. The TDMA part 75, the frequency synthesizer and the receiving parts 73-1, 73-2 are controlled by a control part 83, and specified signals of the control part 83 are supplied to a display/operation part 84.
In the above-mentioned base station equipment, a part of the transmitting-and-receiving parts installed in the transmitter/receiver shelves 55-1 to 55-3 is previously selected to be used for a control channel. Based on control from the base-station control equipment 56 and the shelf control part 60-1, through the control channel, broadcast information is transmitted repeatedly, and a radio channel is set. The previously selected transmitting-and-receiving part communicates and interfaces with networks through the PCM interface part 57 and the synchronous terminal equipment 59.
Next, an operation of the conventional mobile station equipment will be discussed. FIG. 3 and FIG. 4 show flowcharts of the operation of the conventional mobile station equipment shown in FIG. 2. In the control part 83 shown in FIG. 2, a single or a plurality of perch frequencies are previously set. In FIG. 3, when a power is turned on, one of the perch frequencies is set in the frequency synthesizer 82 by the control part 83 (step S1). The frequency synthesizer 82 generates the perch frequency thus set, and provides the local signal of the perch frequency to the receiving parts 73-1, 73-2 and quadrature modulator 80. The receiving part 73-1 measures receive signal strength L1 of a broadcast signal which is received from the base station on the radio channel of the perch frequency (step S2). The control part 83 compares the receive signal strength L1 with the minimum signal strength Lth1 (which is referred to as a threshold level, hereinafter) (step S3). The threshold level Lth1 is a reference level for a connection in a service zone defined by this base station. When the receive signal strength L1 is equal to or larger than the threshold level Lth1, the measured receive signal strength L1 and the perch frequency are stored in a memory (not shown) (step S4). And, when the receive signal strength L1 is smaller than the threshold level Lth1, such a storage process is omitted and the operation proceeds to the next step. The above-mentioned successive processes are repeated for all perch frequencies (step S5).
After the above processes in step S5 are completed, the control part 83 determines whether or not any perch frequency is stored in the memory (step S6). When the perch frequency is not stored in the memory, it is supposed that the mobile station is not in any radio zone (step S7). This condition is referred to as out-of-zone, hereinafter. In this case, the above-mentioned successive processes (step 1 to step 6) are repeated.
When any perch frequency is stored in the memory, the control part 83 sorts the perch frequencies stored in the memory in an order of higher receive signal strengths L1 (step S8). And, the control part 83 selects the perch frequency having the highest receive signal strength in a top priority from the sorted perch frequencies and sets the frequency synthesizer 82 to the a selected perch frequency (step S9). And, subsequently, with the receiving part 73-1, the control part 83 measures a receive signal strength L2 of the broadcast signal which is received on the selected perch frequency (step S10).
The receiving part 73-1 supplies the received broadcast signal to the demodulator 74. The demodulator 74 demodulates the broadcast signal, and generates a baseband signal. The TDMA part 75 analyzes the baseband signal based on a predetermined frame structure, and provides an analyzed result to the control part 83.
The control part 83 determines whether or not the broadcast signal is regularly received by examining data of the broadcast signal (step S1). When the control part 83 determines that the broadcast signal is not regularly received by the examination, the next higher-strength perch frequency in the order of the stored perch frequencies is set to the frequency synthesizer 82, and the successive processes of the steps S9 to S11 are repeated for that perch frequency (step S12). During these processes, when it is determined that the broadcast signal is regularly received by the examination of the data of the broadcast signal, the receive signal strength L2 of the broadcast signal is measured again through the receiving part 73-1 by the control part 83. And, the receive signal strength L2 is compared with the minimum signal strength Lth2 which permits a stand-by operation for receiving a call (step S11'). The minimum signal strength Lth2 is referred to as a down-link stand-by permission level.
When the control part 83 recognizes that the receive signal strength L2 is equal to or larger than the down-link stand-by permission level Lth2 in the above comparison, the process proceeds to the stand-by state mentioned later. When the control part 83 recognizes that the receive signal strength L2 is smaller than the down-link stand-by permission level Lth2, in the same way as the case that the broadcast signal is not regularly received, the frequency synthesizer 82 is set to the next higher-strength perch frequency in the sorted order of the perch frequencies. And, the processes of steps S9 to S11 are repeated in the sorted order until a condition L2.gtoreq.Lth2 is satisfied or a last frequency is set (step S12). The above-mentioned processes of the control part 83 from a power-on timing or the out-of-zone state to the stand-by state, steps S1 to S12 are referred to as an entering zone process, hereinafter.
In the stand-by state shown in FIG. 4, the control part 83 measures a receive signal strength L3 of the radio channel at a given time interval through the receiving part 73-1 (step S13). Then, the receive signal strength L3 is compared with the minimum signal strength Lth3 which permits the stand-by state to be continued (step S14). The least signal strength Lth3 is referred to a down-link stand-by degradation level, hereinafter. When the control part 83 recognizes that the receive signal strength L3 is equal to or larger than the signal strength Lth3 in the above comparison, the process is maintained at the stand-by state. When the control part 83 recognizes that the receive signal strength L3 is smaller than the signal strength Lth3, the mobile station is assumed to be out-of-zone, and the successive processes of steps S1 to S6 shown in FIG. 3 are carried out (step S7 shown in FIG. 3).
When the mobile station is in the stand-by state, the control part 83 supervises an operation from a user through the display/operation part 84. And, the control part 83 examines control information (for example, a selection calling command) which is received from the base station through the antenna 71, the transmit/receive duplexer 72, the receiving part 73-1, the demodulator and the TDMA part 75. Further, the control part 83 detects information (for example, a location registration request) for the mobile station transmitted from the base station based on the predetermined control procedures. Thereby, the mobile station may detect a call (step S15 in FIG. 4), and associated processes with the call are performed (step S16).
In the above processes, the control information (for example, a call request) generated in the control part 83 is put into the TDMA frame by the TDMA part 75. A bit sequence of the TDMA frame is filtered by the waveform-shaping process in the waveform-shaping part 79. And, a filtered signal from the waveform-shaping part 79 is converted to a .pi./4-shifted QPSK signal by the quadrature modulator 80, and is transmitted to the base station through the power amplifier 81 and the transmit/receive duplexer 71-1.
Next,an operation of the conventional base station equipment will be discussed. FIG. 5 shows a flowchart of the operation of the conventional base station equipment shown in FIG. 1. In the base station, the base-station control equipment 56 connected to the base station transmits and receives a variety of control information (for example, a selection calling command, a location registration request, a call request, etc.) with the mobile station equipment located in the radio zone defined by the base station through the base station equipment. And, when any control information from the mobile station equipment is received, the base-station control equipment 56 analyzes the control information (steps S17, 18 shown in FIG. 5), and processes adaptive to these analysis result of the predetermined plural processes are successively carried out (step S19).
In the above description, the down-link stand-by permission level Lth2 and the down-link stand-by degradation level Lth3 may be transmitted to the mobile station by the base station equipment along it with the broadcast information. However, to simplify the description, it is assumed that the mobile station equipment previously has the down-link stand-by permission level Lth2 and the down-link stand-by degradation level Lth3.
Next, a description will be given of disadvantages of the conventional mobile and base station equipment. FIG. 6 shows a conventional control sequence between the mobile station equipment and the base station equipment. In the conventional mobile station equipment, as shown in FIG. 6, when the broadcast information from the base station is regularly received on the control channel, and the receive signal strength of the control channel in the mobile station equipment (which is referred to as a down-link signal strength) is larger than the down-link stand-by permission level Lth2, the mobile station equipment is in the stand-by state on the control channel. The above process is carried out regardless of a level of a signal which the base station receives from the mobile station. Therefore, for the portable-type and the on-vehicle-mountable-type mobile station equipment in which the transmission power is relatively low, the receive signal strength detected in the base station (which is referred to as an up-link signal strength) may be extremely small as compared to the down-link signal strength in the mobile station.
Accordingly, a large difference between the transmission performance of the up-link and down-link radio lines between the base station and the mobile station occurs. In this case, the control signal may not be regularly transmitted and received between the base and mobile stations, and, thus, the radio transmission path for a call may not be established. Even if the radio transmission path is established, a sufficient speech quality of the call may not be obtained and a service quality may be degraded. Furthermore, by the degradation of the quality, a disconnecting process may be forcibly performed based on the control sequence.

Mobile station equipment and base station equipment and control method


The present invention provides a methodology that can develop a more excellent anti-cancer drug than conventional ones for various cancers. Specifically, the present invention provides a method for establishing an artificial cell, comprising treating a cancer cell with an expression vector for a foreign oncogene and then culturing the cancer cell treated with the expression vector under a condition which inhibits an expression or function of an oncogene that is inherent to the cancer cell, and an established artificial cell; a method of screening an anti-cancer drug, comprising evaluating whether or not a test substance inhibits a proliferation of the artificial cell; as well as a method for identifying an oncogene, comprising treating a cancer cell with an expression vector for a test gene and then culturing the cancer cell treated with the expression vector under a condition which inhibits an expression or function of an oncogene that is inherent to the cancer cell.

Currently, anti-cancer drugs are actively researched and developed. Effective techniques for research and development of the anti-cancer drugs may include (1) identification of an oncogene, (2) establishment of an oncogene-expressing cell, and (3) screening for an oncogene targeting drug.
(1) Identification of Oncogene
Anti-tumor effects of molecular targeting drugs that targets a particular oncogene (e.g., gefitinib) have attract attention, and the molecular targeting drugs having the anti-tumor effect have been developed. A method for identifying an oncogene that is promising as a novel molecule to be targeted is utilized in the development of such molecular targeting drugs. An example of such a method for identifying the oncogene is a method in which a gene library anticipated to include an oncogene is introduced into a cell and a gene introduced into the cell, which exhibits a transformation capacity, is selected as the oncogene (hereinafter a conventional identification method 1). For example, Non-patent Literature 1 discloses that a novel oncogene EML4-ALK was found by a transformation experiment utilizing a murine 3T3 cell (non-cancer cell).
Another example of the method for identifying the oncogene is a method in which gene expression is entirely analyzed between cancer cell or cancer tissue samples and normal cell or normal tissue samples using DNA chips or two dimensional electrophoresis and the oncogene is selected from the genes, expressions of which are different between the samples (hereinafter, conventional identification method 2).
(2) Establishment of Oncogene-Expressing Cell
A method for establishing an oncogene-expressing cell may include a method of isolating a cell line naturally expressing an oncogene from a subject as well as a method of introducing an oncogene together with a drug resistant gene (e.g., G418 resistant gene) into a cell and then selecting the cell carrying the oncogene using the drug (e.g., G418).
Patent Document 1 discloses that a cell line capable of proliferating in the presence of a ligand or a ligand-like substance and a drug corresponding to a drug resistant gene can be established by introducing a ligand receptor gene and the drug resistant gene into a cytokine dependent cell line (non-cancer cell), although the establishment of the oncogene-expressing cell is not focused.
(3) Screening for Oncogene Targeting Drug
An example of a method for screening an oncogene targeting drug using a cell is a method of using a cancer cell line naturally expressing an oncogene (hereinafter, conventional screening method 1).
Another example of the method for screening the oncogene targeting drug using the cell is a method of using a cell in which an oncogene has been introduced (hereinafter, conventional screening method 2). For example, Non-patent Literature 1 discloses that the EML4-ALK gene was introduced into a murine IL-3 dependent cell line (non-cancer cell line, Ba/F3 cell line) and effects of a molecular targeting drug that targeted the EML4-ALK gene was verified.
Patent Document 1 discloses that the ligand or the ligand-like substance can be screened by using the aforementioned cell line derived from the cytokine dependent cell line (non-cancer cell line), although the screening for the oncogene targeting drug is not focused.

Method for identifying oncogene, method for establishing oncogene-expressing cell, and method of screening oncogene targeting drug