A method of electrochemical analysis involves contacting fluid samples of first and second different types in a mixed sequence with an electrochemical sensor, and also contacting the sensor with a standard fluid, in order to measure the values of an analytical item, e.g. ionic activity, in the samples with reference to a standard value of the same analytical item in the standard fluid. To improve response of the sensor, at each change in the sequence from the first sample type to the second sample type, the sensor is contacted with a second fluid having a value of the analytical item closer to the mean value of the analytical item in the second sample type than the value of the analytical item in the standard fluid. The method is applicable for example to analysis of blood serum and urine using an ion selective electrode.

1. Field of the Invention
This invention relates to a method and apparatus for electrochemical analysis of fluid samples, and also to an aqueous solution useful in such method and apparatus. The invention is especially applicable in the medical field, but is not limited thereto. The invention will be described below particularly in relation to the analysis of blood serum and urine samples, but is applicable to the analysis of a wide variety of other samples.
2. Description of the Related Art
In electrochemical analysis, the response time of an electrochemical sensor in which ion transport takes place is often relatively slow. It is generally sought to improve the response time and thus the sensitivity of the sensor. One known form of sensor is the ion selective electrode in which a sample to be measured contacts an ion selective membrane containing ligands which specifically transport the ion being measured. An internal solution of the electrode, which typically contains an electrolyte of the gel type, also contains the ion being measured. An electromotive force (emf) is generated in the cell as a result of the concentration gradient across the ion selective membrane, and this emf is measured in order to measure the concentration of the selected ion in the sample solution. Strictly speaking, it is the ionic activity in the sample solution which is measured, not the concentration, but the two are related.
Such ion selective electrodes are used for example in blood serum analyzers. Typically, the prepared sample of blood serum is passed consecutively through three ion selective electrodes, which measure the concentrations of sodium ions, potassium ions and chloride ions in the sample. Such analyzers are nowadays large machines which perform a large number of other analytical measurements on blood samples. For convenience, for example in a hospital, it is also desired to analyze urine samples in the same machine, in particular to measure the concentration of sodium, potassium and chloride ions in a urine sample using the same ion selective electrodes. The problem arises that while the characteristics of samples derived from blood, e.g. serum or plasma, are generally similar, the characteristics of urine in relation to the ion selective electrode are very different from those of samples derived from blood. Because the ion selective electrode has a relatively long response time, its response to a urine sample can be unacceptably slow.
One solution to this problem is to batch the samples, so that urine samples are presented to the ion selective electrodes separately from samples derived from blood. However, this is inconvenient for the operator of the machine, when presented with a large number of samples which arrive for analysis in a random order, or when a particular sample must be analysed urgently.
A further problem in the prior art can be the frequent need to perform a priming operation, i.e. to fill the whole flow passage of the apparatus with a diluting solution, e.g. to put it into a uniform condition. This takes time and consumes diluting solution. Particularly, if samples are batched according to type, priming after each batch is thought necessary.
One known form of blood analysis machine is the "TBA-50S" of Toshiba. To enable serum samples and urine samples in a random order, this machine is arranged to dilute urine samples preliminarily and for this purpose a special dilution line is added. See "TBA-50S Development of Urine Measuring System", Japanese Journal of Clinical Laboratory Automation, 12(4), page 78, 1987. Such analysis machines dilute all samples considerably for the electrochemical analysis, but the additional preliminary dilution of a urine sample leads to very low values of sodium and chloride ions, which then become difficult to measure. Furthermore, if the preliminary dilution is an additional step performed by the operator, this is inconvenient. If the machine performs the additional dilution, the machine must be larger and more complicated.
Another document describing analysis of serum using an ion selective electrode is JP-A-60-73359 (1985), which describes a process in which the ion selective electrode is contacted first with a solution for calibration, i.e. an internal standard solution, then with the serum sample, and then with a cleaning solution which has characteristics similar to those of the internal standard solution. Measurements are taken for the calibration solution and the sample. Attention is also drawn to U.S. Pat. No. 4,680,270 which describes the use of ion selective electrodes in the analysis of blood samples.

Method and apparatus for electrochemical analysis and an aqueous solution for use therein


A mushroom compost compacting system and method includes a roller assembly mounted to a compost receptacle to form a nip, and a web or conveyor to convey mushroom compost to the nip. Mushroom compost is compacted at the nip from an initial compost height to a final compost height. The roller assembly has a roller, a shaft, and fixtures coupled to each end of the shaft. The fixtures are adjustable to define the roller nip height. In one embodiment, the fixtures are mounted to sleeves that engage the sidewalls of the compost receptacle. In another embodiment, the ends of the fixtures are mounted to a support, which may be a joist or a separate channel extending under the floor portion of the compost receptacle, or which may be a post that forms support structure for the compost receptacle.

1. Field of the Invention
The field of the invention is mushroom compost compacting systems, and particularly those systems for composting Phase II or Phase III mushroom composts.
2. Background
Mushroom farming comprises generally six steps: (1) Phase I composting; (2) Phase II composting; (3) spawning; or (2a/3a) Phase III composting; (4) casing; (5) pinning; and (6) cropping. The most used and least expensive mushroom compost is straw-bedded horse manure to which nitrogen supplements and a conditioning agent, such as gypsum, are added. After the compost ingredients have been mixed, watered and aerated in Phase I for a requisite number of days, the compost is pasteurized in Phase II. Pasteurization kills insects, unwanted fungi or other pests that may be present in the compost.
Preparing Phase II mushroom compost can be difficult. One reason for the apparent difficulty with this phase is that pasteurization can last up to two weeks, depending upon the production system used. The time required, as well as other difficulties in maintaining temperature control and eliminating pests during this phase have led many mushroom farmers to purchase pre-pasteurized compost. In many cases, the Phase II compost is pre-mixed with mushroom spawn. Alternatively, Phase III compost is pasteurized, pre-mixed with mushroom spawn and spawn run.
When commercial mushroom farmers purchase pre-pasteurized Phase II or Phase III composts, proper compaction of mushroom beds is still necessary to spawn and grow mushrooms. Moreover, regardless the type of receptacle in which the compost is stored during processing, uniform compaction and density of the compost is beneficial for mushroom cultivation. For maximum yield, mushroom beds should have Phase II and Phase III compost density and compaction that fosters gas exchange, keeps compost temperatures sufficiently low, and prevents spawn kill in the next phase of processing.
Presently, commercial mushroom farmers who purchase pre-pasteurized compost introduce the Phase II or Phase III compost into beds by conveyor and attempt to use spawning machines to compact the compost. These machines, however, are not designed to compact to the degree desired for mushroom cultivation. Furthermore, these machines are less than desirable for commercial mushroom farmers because during operation they also chop up the spawn incorporated into the compost, potentially interfering with the next step in mushroom farming.
Other known compacting systems and methods are impractical for commercial use. One such system uses an assembly with rollers and smoothing plates. In this system, mushroom compost is partially compacted after placement into the mushroom bed. The assembly is then horizontally positioned over the bed and manually guided by two operators located on each side of the bed. This system tends to compact only a surface layer portion of the bed. Compaction to some degree has also been performed by hand after placement of compost in the bed. These time-consuming manual systems and methods make clear the need for improved mushroom compaction systems.
While certain aspects of prior art mushroom compacting systems have been discussed, aspects of these systems are in no way disclaimed and it is contemplated that the claimed invention may encompass one or more aspects of the prior art devices discussed herein.

Mushroom compost compacting system and method


A composite item is fabricated in a device for infusing a layup. The device include a mandrel, vacuum cup and bagging film. The mandrel is to receive the layup. The mandrel includes a reinforcement receiving zone and a resin receiving zone substantially adjacent to the reinforcement receiving zone. The vacuum cup is in cooperative alignment with the resin receiving zone. The bagging film is to generate a gas tight envelope surrounding the reinforcement receiving zone and the resin receiving zone. The vacuum cup is sealed upon the bagging film to generate a chamber above the resin receiving zone.

Laminated materials such as, for example, composites are widely utilized to increase structural rigidity in a wide variety of products. For example, composites are generally utilized by the airplane construction industry to build airframes, structural members of airframes, wings, wing spars, and the like. In some of the most advanced aircraft, where high strength and rigidity and low weight are extremely important, composites may account for a significant portion of the airframe as well as the external surface or skin. Typically, these composites are constructed from a plurality of layers placed over a form. These layers are often referred to as partial or full plies. Each ply may be in the form of unidirectional fiber material, woven fibers in a fabric, braided, or a variety of other conformations. Plies of unidirectional fiber material are often placed in several direction or strand orientations such as, 0°, 90°, ±45°, and the like. The fibers may be made from any of a multitude of natural and/or "man-made" materials such as fiberglass, graphite, Kevlar®, and the like.
In a "dry layup," the plies of reinforcing material are placed on a form or mandrel and then saturated with a resin such as epoxy. If an excess of epoxy is present in the layup, the plies may "float" off the mandrel or create layers or pockets of epoxy that add weight to the layup without adding significant strength. However, if the plies are insufficiently saturated with epoxy, internal and/or external voids may occur. Such voids may result in undesirable material strength properties and/or surface imperfections. While conventional methods and devices have been employed to overcome these issues, these conventional solutions have not been fully successful.
Accordingly, it is desirable to provide a system, apparatus and method for infusing resin into a layup that is capable of overcoming the disadvantages described herein at least to some extent.

Controlled delta pressure bulk resin infusion system


An electrode electrolyte system is provided that is capable of operating in slope sensors in a wide range of temperatures. The eletrolytic system is characterized by a stable conductivity at high temperature and by low toxicity. The slope sensor can be installed in a system containing an Nal solution in propylene carbonate, combined with platinum electrodes.

The present invention relates to new fluid electrode system and in particular a fluid electrode system for use in resistive slope sensors. This fluid electrode system consists of a mixture of an electrolyte and a solvent, and due to its favorable properties, permits a wide variety of technical applications.
A resistive slope sensor, in particular one for the automotive area, is described in DE 19512374 as having a housing which is partially filled with an electrically conducting fluid. The housing contains electrodes for recording measuring signals which are conducted through the housing wall to the outside, where the measuring signals are fed to a plotting unit. That invention proposes that polyether be used as a fluid to serve the function of a sensor. However, because of the toxicity of the proposed materials, their mass application may be fraught with problems.
FR-A2668824 describes fluid-filled sensors, containing as sensor fluid, mixtures based on ethylene glycol and water in equal parts. As the lower working limit for these sensors, the temperature is given as xe2x88x9231xc2x0 C., thus, also ruling out these sensors as a possible solution, since the automotive area requires a working temperature range of  less than xe2x88x9240 to 120xc2x0 C., as well as a flash point  greater than 100xc2x0 C.
Furthermore, WO 96/27892 and DE 19507610 describe fluids which contain as a main component, at least triethyleneglycodimethylether, a compound having mono- or multi OH-functional groups, and a salt which is dissociated within the mixture. Further mixtures that are suitable as electrolytes are described in U.S. Pat. No. 2,852,646, U.S. Pat. No. 2,387,313 and in U.S. Pat. No. 2,927,987.
The sensor fluid described in DE 19597610 represents the best solution to the problem as stated for that sensor and is based on the marginal conditions for its application described in DE 19512374.
However, the disadvantages of that particular sensor fluid are, possible health hazards effected through triethyleneglycodimethylether (see in connection therewith: RTCS No.: XF0665000 2,5,8,1,1-tetraoxadodecane); a likely formation of peroxide when coming in contact with oxygen, and the difficulty of handling the fluids based on the strongly hygroscopic behavior they exhibit, in conjunction with undesirable changes of the electrical properties that occur with the uptake of water, which makes use of these sensors undesirable.
It is thus an object of the present invention to provide an improved sensor fluid-electrode system, obviating the afore-stated drawbacks. In particular, it is the object of the present invention to provide an improved sensor fluid-electrode system for use as a slope sensor which fulfills the marginal conditions as described above and which, at the same time, lacks the problems such as, toxicity, incompatibility with water and formation of peroxide.
Furthermore, the electrode-fluid-system must be able to solve the following technical marginal conditions:
working temperature range xe2x88x9240 to +85xc2x0 C.
ratio of conducting capacity at the working temperature end points xe2x80x9cFactor Fxe2x80x9d
max. 22; computation: (conducting capacity +85xc2x0 C./conducting capacity xe2x88x9240xc2x0 C.)
lowest possible changes in viscosity and level of conductivity though thermal
alteration
no discharge at the electrodes.
In a fundamental solution to the object of the present invention namely, to provide the type of fluid component without the above described disadvantages it has been found that mixing an electrolyte with a solvent provides such an improved fluid-electrode system. Additional components, such as solvent facilitators, stabilizers etc. may also be introduced into the system. Furthermore, the sensor fluid can be made compatible with a particular electrode system of choice.
These objects, and others which will become apparent hereinafter, are attained in accordance with the present invention as further described.
At the outset, the selection of propylene carbonate as a solvent for a fluid component, as described in WO 96127892, is not considered a solution to the object of the invention, since propylene-based electrolytes do exhibit a comparatively large changes in conductivity relative to temperature (compare Example 1). Other fluid components listed there, are conditioned to a lesser degree on the conductivity changes relative to the temperature.
However, the addition of water to the sensor fluids, in particular, the triethyleneglycol dimethylether-based sensor fluids, causes a dramatic decrease in the conductivity condition, thus requiring water-free conditions for the production of the slope sensor, its application, and throughout the life of the slope sensor. Water free conditions poses high demands on the production effort of the slope senor, and in particular also on sealing of the housing, as described in DE-195 12374, since electrodes must be conducted through the housing and the conduits must be sealed. These adverse properties of the fluid systems are amplified further by the hygroscopic characteristics of the triethyleneglycol dimethylether.
It has surprisingly been found, that when propylene carbonate is used as a sensor fluid base, the addition of water causes only small changes in the conductivity condition between the outer limits of the temperature range as is shown in Example 1. This is surprising, since addition of water to various other organic solvents always leads to considerable changes of this condition. Propylene carbonate thus appears to mask available charge carriers (ions) at high temperatures for water.
Advantageously, it follows, that by using propylene carbonate as a solvent base of the fluid component according to the invention, the electrochemical properties, particularly the conductivity-temperature range condition, are very insensitive to contamination by water.
It appears, that a mixture of tetra-alkylammonium halogenides and propylene carbonate solves this object of the invention. These compounds are soluble within the temperature range from xe2x88x9245 to  greater than +100xc2x0 C. in propylene carbonate. These solutions exhibit electrical conductivity. For example, a 0.055% solution exhibits at xe2x88x9240xc2x0 C., a conductivity of 12.5 xcexcS cmxe2x88x921, at 85xc2x0 C., a conductivity of 260 xcexcS cmxe2x88x921. By varying the amount of tetraethylammonium halogenides to be used, conductivity may be adjusted within a wide range of requirements without extensive change of factor F.
To provide a complete solution to the object of the invention, a sensor fluid had to be found which, among others, behaves indifferent to thermal load. As Example 5 illustrates, this is not the case when tetra-alkylammonium halogenides are used as electrolyte.
It has surprisingly been found that the use of sodium iodide as electrolyte solves the above-stated object of the invention. This electrolyte is not taken into consideration at the outset, since electrolytes with metal cations possess the adverse property of reacting with possible disintegration products of the solvent (carbon dioxide) and thereby forming precipitations. However, these disadvantages are alleviated through limiting other conditions during use, and if necessary, by the addition of stabilizers. The examples below illustrate these relations. For example, precipitations occur, at a thermal load above 90xc2x0 C. over a longer period of time when more than 1.5% water is added to the mixture (compare Example 4). Thus, when dibenzo-18-crown-6 (Cas is added, a precipitation of sodium carbonate can be avoided.
One of the decisive criteria for the technical application of the electrolytes described here, the is the long term stability of the electrolyte. Only slight changes in its properties are permissible to occur during transport, storage, production and application of the electrolyte.
In accordance with the invention, no change occurs in a mixture of propylene carbonate and sodium iodide, unless there are outside influences relative to conductivity, factor F, viscosity, boiling point and flash point. The materials used are thermodynamically stable under the usual marginal conditions (usual storage and processing temperature max. 25xc2x0 C.).
When the fluid is used as a fluid component in resistive slope sensors in the automotive industry, it is exposed to a thermal load (up to 85xc2x0 C.) as well as an electrochemical load. A further load may occur during use when substances, such as water and oxygen, diffuse into the housing if the housing is not properly sealed, thereby causing possibly chemical reactions, that occur either directly with the electrolyte, or with the electrolyte-electrode system.
Example 5, compares the thermal load capacity of various electrolytes. As is shown in 5.3, the conductivity does not change at room temperature (measurement accuracy: +/xe2x88x920.5 xcexcScmxe2x88x921) thereby guaranteeing a storage stability. At 85/90xc2x0 C. over 1500h, the conductibilty of the tetra-ethylammonium chloride/propylene carbonate mixture diminishes by 28%, while the conductivity of the Nal containing electrolyte diminishes by only 2-3%.
As example 5.5-5.9 demonstrates, the thermal stability of the NAI is also provided at 120xc2x0 C. Additions to the electrolyte (compare. electrochemical stability, precipitations) have no quantifiable influence.
Any leakage in the housing may lead to the electrolyte coming into contact with water during its use and to react with propylene carbonate to produce 1,2 propanediol and carbon dioxide. Metal carbonate exhibits only little solubility in propylene carbonate. As shown in Example 4, conditions may exist which lead to formation of precipitation in the electrolyte. While no formation of precipitation could be detected under varying conditions with the use of TEtACI (4.1), however, the unsatisfactory thermal stability remains problematic.
Example 4.1-4.6 show, that when using Nal, a certain level of water concentration in the electrolyte should not be exceeded. In those cases where water uptake by the electrolyte cannot be ruled out, precipitation of sodium carbonate can be advantageously avoided by the addition of dibenzo-18-crown-6.
The fluid component according to the invention serves to conduct the alternating electrical current between the electrode system. In order to obtain a slope dependent signal that is stable over a long period of time, it is necessary, to combine the fluid component with an electrode system having long term stability. The sensor fluid-electrode system operates on the principle of measuring the resistance between two electrodes that are immersed only partially within a fluid. Thus a resistance signal with respect to the surface of the immersed part of the electrode is generated, and on the basis of this signal the location of the electrode can be determined.
The measurement of the resistance is effected by conducting an electrical current through the sensor fluid-electrode system, thus leading to a permanent electrical current load. As a basic requirement, the electrode segment, which is immersed in the sensor fluid, must not be changed by the electrical current. Likewise, no polarization layer must be allowed to build up over time, otherwise a variable signal is being measured while the slope position is steady.
In order to solve this problem, not only must electrodes be employed that fulfill these requirements, but also, the levels of electrical current and voltage that are required for measurement must be adjusted, so that a durable long-term system is effected. As a possible solution, non-polarizable electrodes, i.e. silver/silver iodide respectively, silver/silver chloride can be used. However, it cannot be ruled out, that any measuring instrument also measures portions of direct-current and there is always the danger with electrodes of this type, that changes occur in the electrode parts which are immersed within the sensor fluid, since, for example, silver halogenide is completely reducible.
Surprisingly, it has been found, that a long term stable system can be built with polarizable electrodes. Platinum has been proven to be especially suitable for use as electrode material. Likewise, platinum/iridium or ruthenium-mixed oxides are also suitable for use. It has been proven particularly advantageous to put these electrode materials onto a valve metal support, preferably onto a titanium wire, whereby advantageously, the mechanical stability of the valve metal are coupled with the electrochemical properties of the precious metal layer.
The fluid system must likewise be adjusted to the chosen electrode system. A variety of technical difficulties connected with this must be solved by the choice of fluid systems: portions of direct current may cause the formation of a basic border layer near the cathode, and an acidic border layer near the anode. In the presence of water, this can lead to a disintegration of propylene carbonate and subsequently,xe2x80x94when using sodium iodide as electrolytexe2x80x94to a precipitation of sodium carbonate. When using tetraethylammonium chloride, the tetra-ethylammonium ion likewise disintegrates in the vicinity of the anode. Furthermore, when measurement currents are too high, this can generally lead to cathodic and anodic disintegration of the fluid. Thus, it is shown that the use of ammonium salts will, in no case, lead to a satisfactory, long term stable system. It is shown that the object of the invention can only be solved by adjustment of the propylene carbonate-sodium iodide system.
The danger of having an acidic or basic milieu near the electrode can be suppressed through the use of the right electrical currents and voltages. By using a masking material, e.g. di-benzo-18-krone-6, a precipitation of sodium carbonate near the cathode can be suppressed. In accordance with the invention, the problem relating to disintegration by a too high charge level per phase, can be avoided by the addition of redoxactive material, e.g. BHT (2,6 ditert-butyl4-methylphenol). With the combination according to the invention of, at least sodium iodide and propylene carbonate in contact with the electrodes as described, surprisingly, all of the marginal conditions are solved and the properties of the slope sensors with respect to the factor F remain then also constant over long periods of use.
In technical applications, this is of particular importance, where it cannot be ruled out that water is present during use, either when the assembly parts are being filled or, through leakage of the sealing materials.
Furthermore, the fluid as claimed according to the invention exhibits a series of advantages which make them seem particularly suitable for the application in electrical and electronic building parts, to wit, the flash point of the mixture as described above is very high (123xc2x0 C.), the boiling point at 241-242. With the low melting point (xe2x88x9248xc2x0 C.), a broad temperature range for applications is thus provided. Also, the point of ignition of the above described mixture is very high at 510xc2x0 C.
An important advantage is also that the substance is generally recognized as ecologically and toxicologically safe for humans, the fluid being WGKO and neither toxic nor of low toxicity.
A further advantage is the low vapor pressure, thus leading to low rate leakage in sealed hollow bodies (sensors) over the duration of their use.
The electrolytes a described are characterized particularly through their steady conductivity at high temperatures over long periods of time. Furthermore, resistively functioning sensors that are operated by alternate current, require a certain tolerance against portions of direct current, which is advantageously provided with the electrolytes according to the invention.

Fluid electrode system for resistive slope sensors


Disclosed is an apparatus and method for battery management. The present disclosure may significantly reduce the likelihood that a fuse of a battery pack will be melted based on a voltage value of a battery cell to which an error has occurred. Accordingly, the present disclosure may avoid an economic loss and a time loss that may occur when the fuse is incorrectly melted and the battery pack becomes unusable.

Recently, the demand of portable electronic products such as laptop computers, video cameras, and mobile phones is dramatically increasing and development of electric vehicles, hybrid electric vehicle, energy storage batteries, robots, and satellites is briskly proceeding, and in keeping with this trend, studies are actively being conducted on high performance secondary batteries that can be recharged and used repeatedly.
Currently, available secondary batteries include nickel-cadmium batteries, nickel-hydrogen batteries, nickel-zinc batteries, lithium secondary batteries, and the like, and among them, lithium secondary batteries are gaining attention in many fields due to advantages of charging and discharging freely in the absence of a memory effect, a very low self-discharge rate, and a high energy density when compared to nickel-based secondary batteries.
Such a secondary battery may be used as a single battery cell, but for use in a high voltage and/or high capacity power storage device, may be used by connecting multiple battery cells in series and/or in parallel. Also, a secondary battery may be used in the form of a battery pack including a plurality of battery cells and various battery management apparatuses to control the overall charging and discharging operations of the battery cells.
In the research and development of the battery pack, safety improvement of the battery pack or the battery cells is sought to achieve. In the event of an electrolyte decomposition reaction and a thermal runaway phenomenon caused by heat generated due to an internal short circuit, overcharge, overdischarge, or other reasons, the battery cell may explode due to a rapid increase in internal pressure. Particularly, the battery management apparatus provided in the battery pack measures and monitors the voltage for each battery cell to prevent an explosion accident caused by overcharge. If the voltage of the battery cell exceeds a threshold voltage, that is, if the battery cell is overcharged, the battery management apparatus turns off a charge/discharge switch installed on a charge/discharge line of the battery pack to interrupt a high current path. Also, if this protection measure fails, a fuse installed on the charge/discharge line of the battery pack works to protect the battery cell from damage that may subsequently occur due to overcharge. That is, when the battery management apparatus determines that there is a risk of explosion in the battery cell due to overcharge, the battery management apparatus melts the fuse installed on the charge/discharge line of the battery pack to break a circuit to prevent the battery cell from being charged any longer.
The management apparatus transmits and receives data to and from an external device via a communication line to execute various control algorithms. Thus, the management system is generally manufactured in the form of an integrated circuit (IC). However, with the recent development of wireless Internet and use of a high output battery pack, noise or electromagnetic waves of various frequencies may affect the IC. As a result, an error may occur while the IC is measuring the voltage of the battery cell.
If the battery management apparatus determines that the battery cell is overcharged based on an incorrectly measured voltage value and melts the fuse installed on the charge/discharge line, the battery pack becomes unusable. In this case, to render the battery pack usable, a manufacturer or an operator should pick up the battery pack, check the state of the battery cell, and then replace the fuse.
As described in the foregoing, when the fuse included in the battery pack is melted to break a circuit based on an incorrectly measured voltage base, an economic loss and a time loss is considerable. Accordingly, there is a rising need for an algorithm that may reduce the likelihood that a malfunction will occur during a battery cell voltage measuring operation and even a fuse melting operation.

Apparatus and method for battery management with malfunction prevention algorithm


An insulative magnetic layer is disposed between a power source conductor layer and a ground conductor layer of a printed-wiring board. Two pieces of conductors are formed by cutting out a part of the power source conductor layer. Another two pieces of conductors are formed by cutting out a part of the ground conductor layer. The former conductors and the latter conductors are connected by five viaholes. A spiral coil inductor of a spiral form is formed in this way. This inductor has the strengthened inductance owing to the insulative magnetic layer provided therein.

1. Field of the Invention:
The present invention relates to a printed-wiring board, more particularly to a printed-wiring board comprising at least one electronic circuit and a substrate having two or more conductor layers for mounting said at least one electronic circuit.
2. Description of the Prior Art:
It is well known that a printed-wiring board mounted with a circuit element such as a transistor, an IC or an LSI often generates an electromagnetic noise, and hence a failure is sometimes caused in an electronic apparatus itself which has the built-in printed-wiring board or in other related electronic apparatus.
Among causes which generate the failure of the electronic apparatus of this like, the cause of particular large weight is a conductive or a radioactive electromagnetic wave produced by a current (a sneak current) which flows through the parasitic capacity or the parasitic mutual inductance of a circuit, called a common mode phenomenon. Since the generation mechanism of the electromagnetic wave of this kind is complex, an effective countermeasure near the failure generation source which is considered most effective has not been established. Therefore, a conventional countermeasure has been to control the conduction or the radiation of the electromagnetic wave by electromagnetically shielding the whole electronic apparatus with a metallic cover and providing a common-mode choke coil or core for the cable outwardly extending from the apparatus. On the other hand, with reference to the printed-wiring board of the conventional type, as shown in FIG. 2, high frequency capacitors C1-Cn are often connected between power supply terminals 3a-3n and ground terminals 4a-4n of electronic circuits Z1-Zn such as the IC, LSI (hereinafter simply called an electronic circuit) connected respectively to power supply line 1 which corresponds to power source conductor layer 1 and grounding line 2 which corresponds to ground conductor layer 2 of the printed-wiring board. The purpose of this arrangement is to flow the high frequency current, which flows in power supply line 1 accompanying the high frequency operation of electronic circuits Z1-Zn, in high frequency capacitors C1-Cn to decrease (that is, filtering) the high frequency fluctuation of the power source terminal voltage and to restrict the coupling (that is, decoupling) with other electronic circuit sharing power supply line 1. However, in particular, for effectively reducing the fluctuation of the power supply voltage, the conventional printed-wiring board is structured, as shown in FIG. 1, with power source conductor layer 1 made of all flat plate having no wiring in order to lower the impedance of the power supply line. The conventional printed wiring board is structured, as shown in FIG. 1, with insulative board layers 6, which are, e.g., typical resin substrates.
The above conventional printed-wiring board has a problem that a circuit designer can not control the high frequency current which flows in the power supply line accompanying the high frequency operation of said electronic circuit.
In other words, when the power conductor layer is made of a flat plate over the whole area without having wiring, the impedance of the power supply line is small, and hence even if a high frequency capacitor is connected between the power source terminal and the ground terminal of the electronic circuit, it is hard to control the high frequency power source current which flows out to the power supply line, and resultantly the high frequency power source current flows in the decoupling capacitor disposed in the vicinity of other electronic circuits which share the power supply line. Therefore, the analysis of the high frequency power source current with reference to the whole printed-wiring board is very difficult and hence it is unable to strictly select the decoupling capacitor to be used for each electronic circuit.
Further, the distribution of the high frequency power source current on the whole printed-wiring board is very complex. Depending on the arrangement of electronic circuits-on the printed-wiring board or on the operation state of the electronic circuits even if they are in the same arrangement, the high frequency power source current distributes in such a manner to form a large loop, having the probability of introducing the problem of electromagnetic radiation or immunity.
For example, as shown in FIG. 2, electronic circuits Z1 (a large current), Z2 (a medium current) and Zn (a small current) for different high frequency power source currents are connected respectively to both power supply line 1 and ground line 2. Mainly from the mounting and the cost restrictions, capacitors C1, C2 and Cn of capacitance corresponding to respective high frequency power source currents (large capacitance for Z1, medium capacitance for Z2, small capacitance for Z3) are connected to respective electronic circuits. When the electronic circuits on the printed-wiring board operate in this state, since capacitor Cn of small capacitance, connected between the power source terminal and the ground terminal of electronic circuit Zn for small high frequency power source current, has the impedance larger than that of other capacitors, the high frequency power source current of electronic circuit Zn flows into capacitor C2 of medium capacitance (having small impedance compared to that of Zn) connected between the power source terminal and a ground terminal of electronic circuit Z2 for a medium high frequency power source current, or into capacitor C1 of large capacitance connected between the power source terminal and the ground terminal of electronic circuit Z1 for a large high frequency power source current. Further, if the capacitors are of the same type, the frequency characteristic of the impedance becomes different according to each capacitance, and the impedance of the capacitor of small capacitance tends to become smaller than the impedance of the capacitor having the larger capacitance, in the region where the number of the high frequency exceeds some value. Therefore, when viewed in the broad frequency band, electric currents flow to and fro in a complicated way between electronic circuits on the printed-wiring board. As a result, the loop made by the high frequency power source current becomes large or the high frequency current of the common mode is made to flow into such as the cable connected from one printed-wiring board to another printed-wiring board, thereby increasing the conductive or radioactive electromagnetic waves.
These phenomena have caused the electromagnetic interference between the electronic apparatus, that is, EMC problem. Further, for example, high frequency power source voltage fluctuation with reference to one electronic circuit on the printed-wiring board sometimes becomes an issue. In this case, even if the capacitance of a decoupling capacitor in the vicinity of the electronic circuit is increased, it is not effective because the more the capacitance is increased, the more the high frequency power source currents of other electronic circuits flow into the circuit, and consequently it becomes hard to decrease the high frequency power source voltage fluctuation with the probability of failing in securing the high frequency operation of the electronic circuit.
Further, when the latest IC/LSI is used in a logical unit which operates at a low frequency, for preventing the generation of the unnecessary conductive or radioactive electromagnetic waves to be caused due to excessively fast rise time or fall time of a rectangular wave signal of the IC/LSI, sometimes a high frequency filter is inserted in the circuit to slow the rise time and the fall time of the rectangular wave signal of the IC/LSI. However, when the high frequency filter of this like is newly added as parts, the high density mounting efficiency on the printed-wiring board is disadvantageously affected.
Therefore, with the conventional printed-wiring board, it becomes necessary to electromagnetically shield the whole electronic apparatus with metal foil, as described above, to protect against the EMC problem and concurrently control the conduction of the electromagnetic waves by attaching a common-mode choke coil or core for the cable extending outwardly of the apparatus. Still further, with reference to the problem which hinders the high frequency operation of the IC/LSI, it is necessary to meet the problem by mounting capacitors of a required number or more on the printed-wiring board to control the high frequency power source voltage fluctuation of the whole wiring board.

Printed wiring board with integrated coil inductor


A battery is rendered to a consistent discharged state in a two-phase battery discharge operation. In a first of the two discharge phases, a constant discharge current is drawn from the battery until a threshold battery voltage is reached. In the second of the two discharge phases, executed after the threshold battery voltage is reached during the first-phase, a time-varying discharge current is drawn from the battery at a constant battery voltage until a threshold discharge current is reached.

The fully-discharged or "empty" state of a rechargeable battery constitutes a reference point for determining a number of critical characteristics, including the full capacity of the battery as well as the charge remaining (i.e., state of charge (SOC)) following a period of use or dormancy. The SOC itself is typically applied to determine other important battery characteristics, including the DC resistance (DCR), a measure of wear that may be applied, in turn, to quantify the state-of-health of the battery.
Unfortunately, the conventional approach to establishing a fully discharged battery—discharging a fully-charged battery at a constant current for a predetermined time—tends to yield inconsistent results depending, for example on the discharge current rate and battery temperature, as illustrated conceptually in FIGS. 1A and 1B.

Method of controlling battery state using constant-voltage discharge


A unique addition of hydraulic cylinders, valves, switches and a pump to assist the existing air brake system now used on todays tractor-trailer trucks without altering the basic function of the air brake system and provides independent, boosted intermittent braking without expelling the air.

The large tractor truck manufacturers striving to achieve better fuel economy are using redesigned diesel engines. The loads are larger and multiple trailers are being pulled. The requirements for compressed air is growing beyond the on board compressor's capacity. The addition of this hydraulic system not only can assist the existing air brake system, but provides intermittent brakes which has proven to be a much safer, shorter braking action without exhausting their valuable air during intermittent braking.

Combination air/hydraulic intermittent braking system


Cutting wheels equipped with knife assemblies suitable for performing size reduction operations on products, methods of operating cutting wheels, knife holders for such knife assemblies, methods of manufacturing knife holders, and slicing machines capable of utilizing such cutting wheels. The knife assemblies each have a leading edge that faces a direction of rotation of the cutting wheel, a trailing edge oppositely disposed from the leading edge, and a cutting edge on the leading edge. Each knife assembly further has a knife holder having a first surface that faces the products advanced toward the cutting wheel in a feed direction and a registration surface formed in the first surface. The registration surface is defined by at least a first recessed planar surface that is recessed a distance relative to the first surface and defines with the first surface at least a first step therebetween.

The present invention generally relates to methods and equipment for performing size reduction operations on products, including but not limited to food products.
Various types of equipment are known for reducing the size of products, for example, slicing, strip-cutting, dicing, shredding, and/or granulating food products. Certain types of equipment are sometimes referred to as transverse slicers that, as schematically represented in FIGS. 1 and 2, utilize a rotating cutting wheel 10 having radially-extending cutting knives or blades 12 that define a cutting plane through which products 16 are advanced, for example, on a conveyor belt 18, toward the wheel 10 in a feed direction. The cutting wheel 10 typically rotates about a horizontal axis 14 to define a vertical cutting plane. A particular cutting wheel disclosed in U.S. Pat. Nos. 5,992,284 and 6,792,841 is commercially known as the Microslice®, manufactured by Urschel Laboratories, and utilized in a variety of size-reduction machines offered by Urschel Laboratories. The blades of the Microslice® cutting wheel transversely slice products advanced through the cutting plane in a rapid manner to enable high volume production of product slices 20, for example, food slices, of substantially uniform thickness.
FIG. 3 depicts certain aspects of cutting wheels of the type disclosed in U.S. Pat. Nos. 5,992,284 and 6,792,841. Similar to the cutting wheel 10 of FIGS. 1 and 2, FIG. 3 represents a cutting wheel 22 having a rim portion 24 surrounding a hub portion 26, which together support truncated triangular-shaped cutting knife assemblies 28 by means of fasteners 30 so that each knife assembly 28 spans the radial distance between the rim and hub portions 24 and 26 of the cutting wheel 22. Each knife assembly 28 includes a knife blade 32 (shown with hidden lines) carried by a knife holder 34. As evident from FIG. 3, each knife holder 34 has a truncated triangular shape such that the holders 34 have wider and narrower ends, with their wider ends 44 connected to the rim portion 24 and their narrower ends 46 connected to the hub portion 26. Only the cutting edges 36 of the blades 32 are visible in FIG. 3, as the view is that of the side of the cutting wheel 22 facing products as they approach the wheel 22, with the rotation of the wheel 22 indicated by the arrow. Each knife holder 34 defines a registration surface 38 (also referred to as a gauging surface) against which products abut and register during slicing thereof. Each registration surface 38 terminates at a trailing edge 40 that is oppositely-disposed from the cutting edge 36 of the same knife assembly 28, faces the cutting edge 36 of the next adjacent (trailing) knife assembly 28, and cooperates with the cutting edge 36 of the trailing knife assembly 28 to define a gate 42 therebetween. The registration surface 38 and trailing edge 40 of each knife assembly 28 are offset from the cutting edge 36 of the trailing knife assembly 28 in the feed direction (perpendicular to the cutting plane of the wheel 22), such that the gate 42 therebetween defines a slice thickness gap that determines the thickness of a slice produced by the trailing knife assembly 28.
FIGS. 4 and 5 depict views of a knife assembly 28 of the type shown in FIG. 3, and FIGS. 6 through 9 depict various views of the knife holder 34 of the knife assembly 28. The knife holder 34 is generally planar, its trailing edge 40 is relatively blunt, and its oppositely-disposed leading edge 96 has a beveled surface 94. Other than the beveled surface 94 and the registration surface 38 (recessed as discussed below), the holder 34 has a uniform thickness, t1 between oppositely-disposed surfaces 64 and 66 thereof (FIGS. 7 through 9). The knife holder 34 includes fastener receiving apertures 98 through which appropriate fasteners may be received for securing the assembly 28 to the rim and hub portions 24 and 26 of the cutting wheel 22. A knife retainer or clamp 100 is provided, having fastener-receiving apertures 102 through which fasteners 104 extend for assembling the knife clamp 100 to the surface 64 of the knife holder 34 opposite the registration surface 38 and therefore facing away from products approaching the cutting wheel 22. The knife blade 32 is mounted on the beveled surface 94 of the knife holder 34 and secured by the knife clamp 100 and fasteners 104, which are received in threaded apertures 110 in the knife holder 34. The blade 32 preferably further includes apertures 112 that can be aligned with studs 114 on the knife holder 34 to accurately locate the blade 32 on the knife holder 34 and prevent movement of the blade 32 relative to the knife holder 34 after the knife clamp 100 has been secured on the knife holder 34 by the fasteners 104, as illustrated in FIG. 5. The knife clamp 100 may include bores 116 that accommodate the studs 114 and may also engage the studs 114 for alignment and securing purposes.
The registration surface 38 of the knife holder 34 is visible in FIGS. 6 through 9. Relative to the surface 66 at the ends 44 and 46 of the holder 34, the registration surface 38 is recessed in the holder 34 by machining or forming the holder 34 to slope progressively from the leading edge 96 of the knife holder 34 toward its trailing edge 40. The knife holder 34, as noted previously, includes a relatively wider end 44 and a relatively narrower end 46. In order to obtain a uniform slice thickness gap at the gate 42 (FIG. 3) adjacent the trailing edge 40 that will yield slices of uniform thickness produced by the following knife assembly 28, the thickness (t3) of the trailing edge 40 where it intersects the registration surface 38 must be uniform between the wider and narrower ends 44 and 46 of the holder 34. Therefore, the registration surface 38 tapers from the leading edge 96 toward the trailing edge 40 so that its depth (t2) is uniform at its intersection with the trailing edge 40 between the wider and narrower ends 44 and 46 of the holder 34 (FIG. 7). Consequently, the slope of the registration surface 38 must progressively increase from the wider end 44 (FIG. 9) toward the narrower end 46 (FIG. 8) due to the shorter distance that the slope traverses. As a result, the registration surface 38 does not lie in a flat plane, but instead is a twisted or curved surface whose curvature is important for proper and stable registration of products during the slicing operation. A technique for generating the progressively increasing slope of the registration surface 38 is to fixture the knife holder 34 so that a twist is induced in the holder 34 prior to machining the holder 34 to form the registration surface 38. The degree of twist is carefully established and maintained during machining of the holder 34 so that when the holder 34 is released from the fixture, the slope of the registration surface 38 progressively increases corresponding to the degree of twist during machining.
As shown in FIG. 10, unsliced products 48 are advanced on a conveyor belt 50 toward the wheel 22 in a feed direction. The products 48 are conveyed in a manner such that each product 48 is individually supported in a zone between a terminus of the conveyor 50 (the region of the conveyor 50 where the food product 48 separates from the conveyor 50 as it engages the cutting wheel 22). Within this zone, each product 48 is sliced by the blades 32 of the cutting wheel 22 while supported by a supporting surface 54, represented in FIG. 10 as being defined by an "apron" (or shear edge) member 52 that has a shear edge 56 at which the supporting surface 54 terminates. The aforementioned slice thickness gap defined by the axial offset between the registration surface 38 at the trailing edge 40 of one knife assembly and the cutting edge 36 of the blade 32 of the trailing knife assembly 28 is evident from FIG. 10, as is the uniform thickness of a slice 58 produced by the trailing knife assembly 28. As disclosed in U.S. Pat. No. 6,792,841, the apron member 52 promotes the ability with which the cutting wheel 22 is able to precisely and uniformly slice round products, in part as a result of its supporting surface 54 sloping downwardly away from the conveyor 50. It is believed that the downward-sloping supporting surface 54 enables gravity to assist in moving the products 48 toward the knife assemblies 28 and to maintain engagement between the food products 48 and the registration surfaces 38 of the assemblies 28 as the food products 48 leave the conveyor 50. The food products 48 are initially supported by the terminal end of the conveyor 50 and then progressively supported by the supporting surface 54 of the apron member 52 while the food product 48 moves downwardly toward the shear edge 56.
Refinements to the radial cutting blades of slicing machines of the type described above have enabled production of precise, thin, uniform-thickness slices of various products. However, certain challenges are encountered when larger cutting wheels are required for cutting relatively large products, for example, cabbages, lettuce, potatoes, and meat products exceeding about 10 cm. For example, slicing of large products requires a more positive registration of the product against the registration surface 38 of each knife assembly 28 because the linear speed at the outermost radial extent of a larger wheel 22 is relatively greater and the product plane face (the planar surface generated on the product once it is sliced) will need a larger registration surface 38 in order to maintain a high degree of precise slice thickness. Furthermore, the rate at which the slope of the registration surface 38 progressively increases is different for knife holders 34 sized for use in wheels 22 of different diameters, and the machining or forming of the registration surfaces 38 and their progressively increasing slopes incur manufacturing costs.

Methods of manufacturing knife holders of cutting wheels


A clothing system has removable leggings that have two legging portions. Each legging portion has an ankle end and a distal end; the distal end has at least one attachment mechanism and a seam of the distal end has elastic material there within. A shorts portion has a waistband and at least one mating attachment mechanism. A skirt portion is affixed to the shorts portion at the waistband. When worn, each of the legging portions is connected to the shorts portion by the attachment mechanisms and respective mating attachment mechanisms in the shorts portion and the shorts portion substantially covers and hides the distal end of each of the legging portions. When the skirt portion is deployed, the skirt portion substantially covers the shorts portion and, when the skirt portion is not deployed, the skirt portion is worn over the waistband to provide the appearance of a belt.

There are many situations in which one needs to convert to and from clothing that covers one's legs. Often, when moving from outdoors where temperatures require leg covering to indoors where temperatures do not require leg covering, perhaps during exercise, a conversion is desired. Many times, one wears shorts for indoor exercise and wears sweat pants over the shorts while traveling outdoors. This is sufficient for warmth, but requires undressing (removing the sweatpants) before exercise. Furthermore, many people prefer leggings over sweatpants for the way leggings shape their legs, provide support, and are conducive to exercising.
In a similar industry, cargo pants have been introduced with removable leg portions, typically attachable/detachable by a zipper that circumnavigates the bottom of the shorts and top of the leg portions at a location approximately mid-thigh. This type of article of clothing is well suited for outdoor exploration, for example, allowing the leg portion to be removed as temperatures increase during daylight hours, but this style does not bode well for exercise, due not only to the appearance, but to the bagginess of the cargo pants style. Furthermore, even though a flap is often provided to cover the zippers, the area at which the leg portion joins with the short portion provides a detraction from the overall style of the article.
There are many times when a person wishes to be stylish, yet quickly transition to workout dress. For example: squeezing in a power-hour workout during a lunch break; heading to the gym after work; heading to yoga after dropping off a child at school then a run on the beach; meeting friends for coffee or lunch before the gym; grocery shopping after a nice walk in the park with grandchildren; running errands after dance, gymnastics, or tennis; etc. All of these often require some sort of dress change.
Further, there are matters of style that individuals prefer, but often, it is difficult to mass-produce large numbers of color variations between sections of clothing. For example, some people prefer a solid color leg portion with a print pattern skirt or shorts while other people prefer a solid color skirt or shorts with a print pattern leggings, while other people prefer everything to be solid and still other people prefer everything to be of a print pattern, To provide all of these options to buyers, manufacturers would need at least four times the number of items for a given style.
What is needed is a system that will detachably join shorts/skirts to leggings without a visible seam to provide robust reconfigurations and multiple color combinations.


This invention relates to certain benzoxazepinones and benzothiazepinones useful as hypocholesterolemic agents, hypotriglyceridemic agents, antiatherosclerosis agents, antifungal agents, Alzheimer's agents or anti-acne agents.

This invention relates to squalene synthetase inhibitors, pharmaceutical compositions containing such inhibitors and the use of such inhibitors to treat hypercholesterolemia, hypertriglyceridemia, atherosclerosis, fungal infections, acne and Alzheimer's disease in mammals, including humans.
Plasma cholesterol levels have been positively correlated with the incidence of clinical events associated with coronary heart disease (CHD). Thus, pharmacological interventions that reduce cholesterol levels in mammals have a beneficial effect on CHD. In particular, decreased plasma low density lipoprotein (LDL) cholesterol levels are associated with decreased atherosclerosis and a decreased risk of CHD, and hypolipidemic agents used in either monotherapy or combination therapy are effective at reducing plasma LDL cholesterol levels and the subsequent risk of CHD.
Cholesterol metabolism in mammals involves a series of pathways including cholesterol absorption in the small intestine, cholesterol biosynthesis in numerous tissues (primarily the liver and small intestine), bile acid biosynthesis in the liver and reabsorption in the small intestine, synthesis of cholesterol-containing plasma lipoproteins by the liver and intestine, catabolism of the cholesterol-containing plasma lipoproteins by the liver and extrahepatic tissues and secretion of cholesterol and bile acids by the liver.
Cholesterol synthesis occurs in multiple tissues, but principally in the liver and the intestine. It is a multistep process starting from acetyl-coenzyme A catalyzed by a series of enzymes including hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase, HMG-CoA synthase, squalene synthetase, squalene epoxidase, squalene cyclase and lanosterol demethylase. Inhibition of catalysis of these enzymes or blocking HMG-CoA reductase gene expression is recognized as an effective means to reduce cholesterol biosynthesis (thus inhibitors thereof are referred to as cholesterol synthesis inhibitors) and can lead to a reduction in cholesterol levels. For example, there are known HMG-CoA reductase inhibitors (e.g., lovastatin, simvastatin, pravastatin, fluvastatin, atorvastatin, rivastatin) that are used for the treatment of hypercholesterolemia.
Recently adopted National Cholesterol Education Program guidelines recommend aggressive lipid-lowering therapy for patients with pre-existing cardiovascular disease or for those with multiple factors that place them at increased risk.
The term squalene synthetase inhibitor refers to compounds that inhibit the condensation of 2 molecules of farnesylpyrophosphate to form squalene, a reaction that is catalyzed by the enzyme squalene synthetase. Such inhibition is readily determined by those skilled in the art according to standard assays (Meth. Enzymol. 1969; 15: 393-454 and Meth. Enzymol. 1985; 110:359-373 and references contained therein). A summary of squalene synthetase inhibitors has been compiled (Curr. Op. Ther. Patents (1993) 8614). European patent publication 0 567 026 A1 discloses certain 4,1-benzoxazepine derivatives as squalene synthase inhibitors and their use in the treatment of hypercholesterolemia and as fungicides. European patent publication 0 645 378 A1 discloses certain condensed seven- or eight-membered heterocycles as squalene synthetase inhibitors and their use in treatment and prevention of hypercholesterolemia and fungal infections. European patent publication 0 645 377 A1 discloses certain benzoxazepine derivatives as squalene synthetase inhibitors useful for the treatment of hypercholesterolemia or coronary sclerosis. European patent publication 0 611 749 A1 discloses certain substituted amic acid derivatives useful for treatment of arteriosclerosis. European patent publication 0705607 A2 discloses certain condensed seven- or eight-membered heterocyclic compounds useful as antihypertriglyceridemic agents. PCT Publication WO 96/09827 discloses certain combinations of cholesterol absorption inhibitors and cholesterol synthesis inhibitors including benzoxazepine derivatives and benzothiazepine derivatives. European patent publication 0710725 A1 discloses a process for producing certain optically active compounds, including benzoxazepine compounds, having plasma cholesterol and triglyceride lowering activities.
Thus, although there are a variety of hypercholesterolemia therapies, there is a continuing need and a continuing search in this field of art for alternative therapies.


A stringed instrument including strings supported by bridges, which are fixed to a body, and a nut fixed to a neck. The strings are supported in a manner enabling vibration of each string. The nut includes a nut body and a fastener. The fastener is formed by pressing members and adjustment screws. The pressing members press the strings against the nut surface so that the strings are fixed to the nut surface. A projection projecting toward the strings is formed on an end portion of the nut. The strings are supported by the nut so as to contact the top surface of the projection. This enables each string to vibrate while being in constant contact with the projection and prevents each string from coming into contact with the nut or fastener. Thus, abnormal noise is not generated.

The present invention relates to a stringed instrument and to a stringed instrument nut for use in a stringed instrument such as an electric guitar.
Referring to FIG. 7, a typical electric guitar typically includes a body 61, a neck 62, and a plurality of strings 64. Tailpieces 63 and bridges 67 are arranged on the body 61 opposite to the neck 62. A stringed instrument nut (hereafter simply referred to as a "nut") 68 is arranged on the neck 62. Pegs 66, which form a tuning device, are attached to a head 65, which is set on a distal portion of the neck 62. Each string 64 has a basal end fixed to the corresponding tailpiece 63 and a distal end wound around and fixed to the corresponding peg 66. The bridges 67 and the nut 68 support the strings 64 in a state spaced from the surfaces of the body 61 and the neck 62. In this state constant tension, is applied to each string 64. When plucked, each string 64 vibrates in a state supported at contact points with the corresponding bridge 67 and the nut 68. When each string 64 vibrates, vibration in a basic-mode and vibration in wavelengths differing from that of the basic-mode vibration are mixed in a complicated manner to create a tone unique to a stringed instrument.
The electric guitar may be played using techniques known as arming and bending. Arming is a technique for changing the tones of the strings 64 by operating a tremolo arm and simultaneously changing the tensions of all the strings 64. Bending is a technique for changing the tone of each string 64 by individually changing the tension of each string 64. When the electric guitar is played using these techniques, the tension of each string 64 changes greatly. As a result, the position of each string 64 with respect to the nut 68 changes greatly. After the electric guitar is played with these techniques, the strings 64 may fail to return to their original positions because of friction resistance between the strings 64 and the nut 68. As a result, the strings 64 may go out of tune and affect the playing of the electric guitar. Each string 64 is tuned by turning the corresponding peg 66 to tighten or loosen the string 64 and adjust the tension on the string. A strong force may be applied to the peg 66 particularly when the string 64 is under high tension. This may reversely rotate the screw of the peg 66 and change the position of the peg 66.
To solve the above problems, Japanese Laid-Open Patent Publication No. 2003-122367 and U.S. Pat. No. 4,171,661 describe electric guitars that include a fastener for fixing strings to a nut. Referring to FIGS. 8 and 9, in the structures described in these documents, a surface 71 of a nut 68 is smoothly curved. Further, support walls 72 are formed on opposite ends of the nut 68. Each support wall 72 has a plurality of support grooves 73 for supporting strings 64. The support grooves 73 of one support wall 72 face the support grooves 73 of the other support wall 72. An inner bottom surface 73a of each support groove 73 is substantially flush with the nut surface 71. Each string 64 is received by two opposing support grooves 73 so as to restrict movement of each string 64 in the lateral direction of the neck 62.
Each string 64 is fixed in a state contacting the surface 71 of the nut 68 by a fastener 90. The fastener 90 includes pressing members 74 and adjustment screws 75. The pressing members 74 are arranged on the nut surface 71. The adjustment screws 75 fasten the pressing members 74 to the nut surface 71. A through hole 77 extends through the central portion of each pressing member 74. The adjustment screws 75 are inserted through the through holes 77. The adjustment screws 75, which are inserted through the through holes 77 of the pressing members 74, are mated with screw holes 76, which are formed in the nut surface 71. When the adjustment screws 75 are tightened, the pressing members 74 press the strings 64 against the nut surface 71 to securely fix each string 64. The fastener 90 prevents the electric guitar from going out of tune even when the electric guitar is played many times using the arming technique or the bending technique. The fastener 90 further prevents the position of each string 64 from changing after tuning.
However, when the strings 64 are securely fixed to the nut 68, stress may concentrate on points at which the strings 64 come in contact with the two ends 78a of each pressing member 74. In such a case, the strings 64 would have a tendency to break at these contact points. Accordingly, the curvature of the ends 78a of each pressing member 74 is smaller than the curvature of the other parts of the pressing member 74. This forms a clearance 79 between an end 78a of the pressing member 74 and the string 64 so that the pressing member 74 is slightly spaced from the nut surface 71. This structure reduces concentration of stress on each string 64. However, interference between each string 64 and the nut 68 may generate abnormal noise.
The nut 68 functions to stably support each string 64. It is thus preferable that the distal end of the nut 68 be sharp like a blade edge. However, when the nut 68 supports a string 64 with a sharp edge, only one point of the string 64 is supported by the edge. As a result, stress concentrates on the supported point of the string 64. This may easily break the string 64 or form a bending depression in the string 64 at the support point. Therefore, it is preferable that the nut 68 be formed so that its nut surface 71 is smoothly curved. More specifically, it is preferable that the nut 68 be formed so that the nut surface 71 extends, for example, along an arc. The nut 68 having the smoothly curved nut surface 71 enables a string 64 to be supported at one point and prevents stress from concentrating on that support point. However, when the nut surface 71 is smoothly curved, each string 64 approaches the nut surface 71 at locations close to the point of contact with the nut surface 71 and are gradually spaced from the nut surface 71 at locations farther from the point of contact. Accordingly, when vibrating, each string 64 has a tendency of coming into contact with the nut surface 71 and thus generating abnormal noise.
The generation of abnormal noise due to the nut 68 will now be described with reference to FIGS. 10(A) to 10(C). In the prior art, the nut 68 is shaped as shown in FIG. 10(A). The nut 68 minimizes the clearance formed between each string 64 and the nut surface 71. In this case, the angle a between the string 64 and the inner bottom surface 73a of the support groove 73 is substantially zero. Further, the string 64 is in contact with the nut surface 71 at an end portion of the nut 68 (as indicated by the ▴ symbol in FIG. 10(A)) when the string 64 is still. In this state, the pressing member 74 presses the string 64 against the nut surface 71 at a fixed point 80, as shown in FIG. 10(A). However, when the string 64 vibrates, the string 64 repeatedly comes into contact with and separates from the inner bottom surface 73a of the support groove 73 as shown in FIG. 10(B). In such a case, the string 64 may generate abnormal noise.
To solve this problem, the angle α between the string 64 and the inner bottom surface 73a of the support groove 73 may be changed so that it is greater than a predetermined value as shown in FIG. 10(C). In this case, the string 64 is supported in a state inclined relative to the nut 68. This keeps the point of contact between the string 64 and the inner bottom surface 73a of the support groove 73 located at the end portion of the nut 68. Referring to FIG. 7, the angle α is affected by various factors including the height of the bridges 67, the angle at which the neck 62 is connected to the body 61, the deformation amount of the neck 62, the shape of the surface to which the nut 68 is attached, and the method for fixing the nut 68. These various factors must be taken into consideration when determining the predetermined value angle α so that the point of contact between each string 64 and the nut 68 is maintained at the edge portion of the nut 68 not only when the strings 64 are still but also when the strings 64 are vibrating.
However, each string 64 is formed by a piano wire or by winding a metal wire around a piano wire, which serves as a core, in a coiled manner. The strings 64 formed from such a material are highly rigid and not flexible. It is thus difficult to extend the strings 64 along the nut surface 71 and bend the strings 64 at predetermined positions just by increasing the angle α between the strings 64 and the inner bottom surfaces 73a of the support grooves 73. As a result, the strings 64 separate from the nut surface 71 and form a gap between each string 64 and the nut surface 71. This may generate abnormal noise due to contact between each string 64 and the nut surface 71. For this reason, the fastener 90 is strongly required to minimize the generation of abnormal noise in addition to fixing each string 64 to the nut 68.

Stringed instrument nut and stringed instrument


An exemplary prism sheet includes a transparent main body. The transparent main body includes a first surface and a second surface. The first surface and the second surface are on opposite sides of the main body. The first surface of transparent main body is flat. The second surface defines a plurality of parallelogram microstructures. Each parallelogram microstructure defines four adjacent triangular pyramid depressions.

1. Field of the Invention
The present invention relates to a prism sheet, particularly to a prism sheet employed in a backlight module.
2. Description of the Related Art
Referring to FIGS. 7 and 8, a typical direct type backlight module 100 includes a frame 11, a plurality of light sources 12, a light diffusion plate 13 and a prism sheet 10. The light sources 12 are disposed in an inner side of the frame 11. The light diffusion plate 13 and the prism sheet 10 are disposed on the light sources 12 above a top of the frame 11 in that order. The light diffusion plate 13 includes a plurality of diffusing particles (not shown) configured for diffusing light. The prism sheet 10 includes a transparent substrate 101 and a prism layer 103 formed on a surface of the transparent substrate 101. The prism layer 103 forms a plurality of elongated V-shaped ridges 105.
In use, light from the light sources 12 enters the diffusion plate 13 and becomes scattered. The scattered light leaves the diffusion plate 13 to the prism sheet 10. The scattered light then travels through the prism sheet 10, and is refracted out at the elongated V-shaped ridges 105 of the prism sheet 10.
The refracted light leaving the prism sheet 10 is concentrated at the prism layer 103 and increases the brightness (illumination) of the prism sheet 10. The refracted light then propagates into a liquid crystal display panel (not shown) disposed above the prism sheet 10.
However, although light from the light sources 12 enters the diffusion plate 13 and becomes scattered, after the light leaves the prism sheet 10, strong light spots of the light sources 12 direct above the light sources 12 are often formed.
In order to reduce or eliminate the strong light spots of the light sources 12, the backlight module 100 should further include an upper light diffusion film 14 disposed on the prism sheet 10. However, although the upper light diffusion film 14 and the prism sheet 10 are in contact with each other, a plurality of air pockets may still exist around the boundaries of the light diffusion film 14 and the prism sheet 10. When the backlight module 100 is in use, light passes through the air pockets, and some of the light undergoes total reflection by the air pockets along one or another of the corresponding boundaries. In addition, the upper light diffusion film 14 may absorb a certain amount of the light from the prism sheet 10. As a result, a brightness of light illumination of the backlight module 100 is reduced.
Therefore, a new prism sheet is desired in order to overcome the above-described shortcomings.

Prism sheet having parallelogram microstructures


A pair of glasses comprises a frame. A first progressive addition lens in the frame comprises a distance portion and a near portion. Diopter power and base in prism gradually increase from the distance portion to the near portion. A second progressive addition lens in the frame comprises a distance portion and a near portion. Diopter power and base in prism gradually increase from the distance portion to the near portion. Base in prism in the first lens may be different from in the second lens. Amount of base in prism may vary in a range of about 0 to 1.5 diopters.

With normal vision, an individual is able to change focus for different distances. Ideally, an individual is able to focus on distant objects, referred to as distance vision, and on near objects, referred to as near vision. The optical system of the eye uses numerous muscles to focus for both distance and near vision. These muscles allow the eye to adjust focus when transitioning between distance vision and near vision. There are various responses involved in changing focus from distance vision to near vision. These include making the image clearer, the eyes turning in or out, and pupils changing size. If the eyes do not turn in enough with near vision, for example, then the individual would see double.
Presbyopia is a natural deterioration of near vision caused by loss of flexibility in the eye's lenses as one ages. This can be compensated by wearing "reading" glasses having lenses which correct refraction errors so that the eye does not have to focus as much. Often with presbyopia, the person does not need distance correction, but rather only near correction. To avoid continually taking the eyeglasses on and off, bifocals may be used. Bifocals enable the person to see at different distances. Particularly, bifocals are generally used when the eye can no longer correctly change focus from distance to near. Progressive addition lenses (PALs) include a distance portion and a smooth, graduating, continuous change in dioptic power to a near portion. PALs have no lines or edges visible between changes in dioptic power.
When a person transitions from looking through the distance portion to the near portion with bifocal lenses, the eyes do not need to focus to the same extent, because of the increase in dioptic power, as without the bifocals. As a result, there is a decrease in accommodative convergence, meaning that the eyes do not try to converge as much. This results in eye strain because the eyes subsequently use additional fusional convergence to converge for near.
The present invention is directed to solving one or more of the problems discussed above, in a novel and simple manner.

Multi-focal ophthalmic lens with base in prism


A wireless communication system for transmitting signals having a wireless positioning system being responsive to incoming signals for processing the same to generate coordinate information for determining the position of said wireless communication system, in accordance with an embodiment of the present invention. The wireless communication system further includes a phase controller module being responsive to said coordinate information for controlling the phase of the output signals for transmission in a specified direction by performing beamforming, said wireless communication system for performing beamforming to increase the range of transmission of said output signals.

1. Field of the Invention
The present invention relates generally to the field of remote wireless communication and particularly to a method and apparatus for beamforming with global positioning and orientation systems.
2. Description of the Prior Art
More recently and with the advent of wireless communication systems remote and wireless communication is gaining more popularity among common users. An example is a highway with several base stations. If a vehicle is within the range of a base station information regarding the location and neighborhood may be exchanged between the vehicle and the base stations.
Currently base stations employ beamforming to increase the range and bandwidth of communication systems. For example, in the conventional cellular phones, the base station performs beamforming to communicate with each of the clients resulting in a substantially large data base to track the numerous vehicles on the road. This is sufficient for cellular phone and other voice related communication systems since the bandwidth required is relatively narrow and the range is relatively long.
Alternatively, in a wireless local area network (LAN) the bandwidth is substantially wide but the range is relatively short. Since wireless LAN is often used indoor, such as in an office environment, the relatively short range is acceptable.
The conventional communication systems have reached theoretical limit. The more recent WIMAX communication systems have range and throughput in the middle. Thus, it is desirable to provide a means and apparatus for long range high throughput communication with dramatic broadband system improvements.

Beamforming with global positioning and orientation systems


A method of depositing a non-conductive barrier layer onto a metal surface wherein the resistance of the metal remains substantially unchanged before and after the non-conductive barrier layer deposition. The deposition process provides a low temperature processing environment so as to inhibit the formation of impurities such as silicide in the metal, wherein the silicide can adversely increase the resistance of the underlying metal.

1. Field of the Invention
This invention relates to integrated circuit processing and, more particularly, to a process for depositing a non-conductive barrier layer such as a nitride film onto a copper surface.
2. Description of the Related Art
A high density integrated circuit typically comprises numerous electrical devices and conductors formed on multiple layers of conducting and semiconducting material that are deposited and patterned in sequence onto a substrate surface. Additionally, insulating material is typically positioned between the individual devices so as to electrically isolated the devices from one another. In particular, intermediate insulating layers, better known as interlevel dielectrics (ILDs), are typically interposed between conducting layers in a circuit so as to electrically isolate components formed on adjacent layers. The insulating layers inhibit electrical shorts and preserve device integrity.
An integrated circuit is operable when its individual components are interconnected with an external source and with one another. In particular, designs of more complex circuits often involve electrical interconnections between components on different layers of the circuit as well as between devices formed on the same layer. Such electrical interconnections between components are typically established through electrical contacts formed on the individual components. The contacts provide an exposed conductive surfaces on each device where electrical connections can be made. However, in a multilayer, high density integrated circuit, the components are often buried in internal sublayers of the circuit where insulating material are deposited over the components making the establishment of electrical contacts difficult.
One method of creating electrical contacts on devices located in the sublayers of the circuit is by forming openings in the interlevel dielectrics (ILDS) that are deposited over the components. The openings, known as contact vias or holes, typically extend downwardly from a top surface of the ILD to the layer containing the electrical devices so that a top surface of the device is exposed. Furthermore, the openings are then filled with a conductive material, such as copper, which effectively establishes electrical contact for components located underneath the ILD.
In addition to contact vias, trenches can also be etched onto the surface of the insulating material in a desired pattern for a conductor layer in a process that is commonly known as the damascene process. In a typical damascene process, the trenches are etched on the surface of the insulating material comprising an ILD and subsequently metalized so as to produce integrated conductors. In particular, the trenches are metalized in a similar manner as that of the contact vias wherein the trenches are filled with a conductive material so as to establish a desired conductive path.
The metalization process generally involves depositing a layer of conductive material such as copper into the vias or trenches, thereby interconnecting electrical devices and wiring at various levels. In a multilayer integrated circuit assembly, an insulating layer is typically deposited onto the metalized vias or trenches so as to electrically isolated the metalized vias or trenches from additional circuit layers that will be formed in a stacked configuration above the vias or trenches. In particular, the insulating layer typically comprises an oxide material such as silicon dioxide wherein the oxide electrically isolates devices formed on adjacent circuit layers. Disadvantageously, however, the oxide layer will lose its insulating properties when copper or other conductive material diffuses from the underlying adjacent layer into the oxide layer. In particular, metal that migrates into an insulating oxide layer can effectively short out the devices electrically isolated by the layer.
To address this problem, a non-conductive barrier layer is generally interposed between the conductive layer and the adjacent insulating layer wherein the barrier layer inhibits metal from diffusing into the insulating layer. In particular, a non-conductive barrier layer typically comprises a nitride film and is preferably positioned between a top surface of a copper wiring layer and a bottom surface of an adjacent oxide layer so as to inhibit copper from migrating upwardly into the oxide layer. Furthermore, the nitride film can be deposited onto the copper surface by using well known deposition techniques such as evaporation, sputtering, chemical vapor deposition, or plasma enhanced chemical vapor deposition (PECVD).
However, one disadvantage of the standard nitride PECVD process is that the nitride film is known to react with a top surface of the copper layer during the deposition process and will consequently alter the electrical properties of the copper. In particular, the copper and nitride reaction is shown to substantially increase the copper line resistance, which in turn will delay signal transmission between devices. Slow signal transmission is not favored in most semiconductor devices, particularly in high speed, high density integrated circuits. Furthermore, high speed integrated circuits generally require conductors with low electrical resistance so as to facilitate current flow and signal transmission. Therefore, a reduction in copper line resistance is not only desirable but necessary in light of the constant demand for integrated circuits with higher speed and increased device density.
Hence, from the foregoing, it will be appreciated that there is a need for a process of depositing a non-conductive barrier layer so that any increase in the electrical resistance of the underlying conductive wiring or contact is reduced. To this end, there is a particular need for a process of depositing a non-conductive barrier layer wherein the barrier layer will not unfavorably increase the copper line resistance.
The aforementioned needs are satisfied by the method of forming a conductive interconnect integrated circuit of the present invention. In one aspect, the present invention comprises a method of depositing a layer of non-conductive barrier film onto a layer of conductive material wherein the deposition process does not affect the electrical resistance of the metal, so that the resistance of the conductive material remains substantially the same before and after the deposition of the non-conductive barrier layer.
In one embodiment, the method comprises depositing a silicon nitride non-conductive barrier layer onto a copper surface is provided wherein the method includes a low temperature plasma enhanced chemical vapor deposition process (PECVD) wherein the PECVD process temperature range is held between 150 C.-300 C. In particular, the low temperature range as disclosed in the present invention is shown to inhibit a reaction between the silicon nitride and copper that typically occurs during the standard high temperature (400xc2x0 C.) silicon nitride PECVD process. Such reaction between the silicon nitride and copper is generally not favored as it results in the formation of silicide in the copper, which in turn will unfavorably increase the line resistance of the copper.
Furthermore, the undesired silicide formation in copper is also known to occur in a reaction between the silane gas used as part of the PECVD process and the exposed copper surface when the PECVD process is conducted in a high temperature environment as taught by prior art. In contrast, the process parameter as disclosed by the preferred embodiment is shown to inhibit this particular reaction between the silane gas and copper so as to further inhibit the formation of silicide in copper. Alternatively, a layer of amorphous silicon carbide is also shown to be an effective non-conductive barrier layer that does not unfavorably increase the resistance of the copper. Preferably, the amorphous silicon carbide is deposited onto the copper surface using a similar PECVD process with a process temperature of approximately 400 C.
From the foregoing, it will be appreciated that the aspects of the present invention provide a method of depositing a non-conductive barrier layer onto a metal surface without increasing the resistance of the metal. In particular, the method provides a novel low temperature plasma enhanced chemical vapor deposition (PECVD) process wherein the low temperature processing environment is shown to inhibit the formation of silicide in the copper, thereby avoiding the undesired increase in copper line resistance that will otherwise result from using known PECVD process parameters. These and other objects and advantages of the present invention will become more apparent from the following description taken in conjunction with the following drawings.

Low temperature nitride used as Cu barrier layer


There is provided a beraprost sodium-containing nanoparticle that contains beraprost sodium among other prostaglandin I2 (prostacyclin) derivatives, which are therapeutic agents for pulmonary hypertension. The beraprost sodium-containing nanoparticle is obtained by making beraprost sodium hydrophobic using a metal ion and allowing the hydrophobic beraprost sodium to react with poly-L-lactic acid or a poly(L-lactic acid/glycolic acid) copolymer, and a poly-DL- or L-lactic acid-polyethylene glycol block copolymer or a poly(DL- or L-lactic acid/glycolic acid)-polyethylene glycol block copolymer. The beraprost sodium-containing nanoparticle excels in sustained release of an active ingredient, reduces a side effect, and furthermore, has an excellent drug retention in the blood. Therefore, the beraprost sodium-containing nanoparticle is quite outstanding particularly regarding the sustainability of the medicinal effect.

Pulmonary hypertension is a disease resulting from increased blood pressure in the pulmonary artery (pulmonary arterial pressure) that is caused by blood flow damaged by a stenosis of the lumen of a pulmonary arteriolar located in the periphery of the vessel for sending blood from the heart to the lungs (pulmonary artery).
The treatment of this disease is performed by administration of a pulmonary vasodilator, which secures blood flow and reduces the pulmonary arterial pressure, thereby reducing the workload of a dilated heart or a thickened pulmonary vessel. Various prostaglandin I2 (prostacyclin) derivatives are clinically used.
The first pharmaceutical agent whose clinical application became possible is epoprostenol, which is prostaglandin I2 (prostacyclin) derivatives. Epoprostenol is a biosynthesized form of a substance that naturally occurs in the living body and has a pulmonary vasodilation effect. Prostacyclin activates adenyl cyclase via a prostacyclin receptor on vascular smooth muscle and increases the concentration of cAMP, and thereby relaxes the vascular smooth muscle and exerts the pulmonary vasodilation effect.
Furthermore, this pharmaceutical agent is believed to have an antiplatelet effect and a growth inhibitory effect on smooth muscle as well. In previous studies, the three-year survival rate for an untreated primary pulmonary hypertension group was about 40%, while that for a group treated with epoprostenol was about 70%. This demonstrates that epoprostenol improved a vital prognosis remarkably. Thus, the therapeutic effect of this pharmaceutical agent may be considered practically established.
The above-mentioned epoprostenol has a very short half-life in blood of about 2 to 3 minutes. Furthermore, epoprostenol has a chemical half-life of only about 10 minutes, wherein the chemical half-life serves as a measure of chemical stability. Therefore, a continuous intravenous administration of epoprostenol is required to achieve a stable therapeutic effect. Additionally, at the time of its administration, the continuous intravenous administration has to be performed by dissolving epoprostenol using a liquid to dissolve it and by using a combination of a special catheter that is inserted into a central vein and an infusion pump. This infusion pump (small precision pump for infusion of a pharmaceutical agent) can secure administration rate of 2 ng/kg epoprostenol per one minute. Therefore, epoprostenol is a pharmaceutical agent that gives a highly negative impact to a patient's QOL.
However, the therapeutic effect of epoprostenol on pulmonary hypertension is very remarkable. Accordingly, various prostacyclin derivatives have been recently under development, and development of more stable prostaglandin I2 (prostacyclin) derivatives has been under investigation. As a result, beraprost sodium, which has a relatively long half-life, has appeared as one of the more stable derivatives.
The above-mentioned beraprost sodium is a prostacyclin derivative developed in Japan. Beraprost sodium has a great advantage over other prostacyclin derivatives in that it has a biological half-life of about 1.1 hours and moreover a long chemical half-life of about 10 days, and its oral administration is possible.
Beraprost sodium was originally approved as a therapeutic agent for arteriosclerosis obliterans. Later, clinical trials for primary pulmonary hypertension and pulmonary hypertension that developed as a complication of a collagen disease were performed, and it was found that treatment by administrating beraprost sodium for three months significantly decreased the pulmonary vascular resistance. Consequently, beraprost sodium was approved as a therapeutic agent for primary pulmonary hypertension and presently is widely used as a first-line drug for pulmonary hypertension.
However, a prostacyclin-based pharmaceutical agent tends to show its vasodilation effect relatively concentration-dependently, based on the experiences of using epoprostenol as a therapeutic agent for continuous intravenous infusion. Therefore, in order to achieve a sufficient therapeutic effect, it is necessary to keep the blood concentration of beraprost sodium stable and as high as possible.
It has been published that the time to reach the maximum blood concentration (Tmax) is 1.42 hours and the maximum blood concentration (Cmax) is 440 pg/mL after conventional oral administration of 100 μg of a beraprost formulation. Therefore, although the blood concentration of beraprost sodium increases relatively rapidly and its vasodilation effect is exerted after this pharmaceutical agent is taken, its medicinal effect disappears quickly since the half-life of the blood concentration is only 1.1 hours, which is problematic. Furthermore, since an increased blood concentration of this pharmaceutical agent leads to a side effect such as decreased blood pressure, an intravenous administration that was expected to be efficacious was not possible.
Therefore, there is an urgent need to develop a formulation that keeps a sufficient and lasting blood concentration of beraprost sodium for a long time.
Aside from this, the present inventors have previously carried out various studies aimed at encapsulating a drug in a microparticle or a nanoparticle made by using a poly(lactic acid/glycolic acid) copolymer (that may also be referred to as "PLGA" hereinafter) or a poly lactic acid (that may also be referred to as "PLA" hereinafter).
For example, the present inventors have applied a patent relating to a drug-containing nanoparticle that excels in the targeting of an affected area and sustained release, and moreover, that reduces hepatic accumulation of the drug and enhances the drug retention in the blood (Patent Literature 1). This drug-containing nanoparticle is obtained by making a low molecular weight drug with a negatively charged group hydrophobic using a metal ion and allowing the hydrophobic drug to react with a poly lactic acid-polyethylene glycol block copolymer or a poly(lactic acid/glycolic acid)-polyethylene glycol block copolymer, and a poly lactic acid or a poly(lactic acid/glycolic acid) copolymer, thereby encapsulating the drug into the resultant nanoparticle.
Furthermore, the present inventors improved the above-mentioned technique further and have provided a nanoparticle containing a low molecular weight drug with a negatively charged group, wherein the nanoparticle excels in sustained release. This nanoparticle targets the low molecular weight drug with a negatively charged group to an affected area efficiently, excels in sustained release of the drug, and reduces the side effect of the drug by reducing its hepatic accumulation (Patent Literature 2).
The present inventors assumed that such a nanoparticle formulation that is obtained by applying the techniques described in these patent literatures to a prostaglandin I2 (prostacyclin) derivative and making a nanoparticle containing it would excel in sustained release of the drug and keep a lasting blood concentration of the drug. Thus, the present inventors investigated the preparation of a nanoparticle of a prostaglandin I2 (prostacyclin) derivative.
Consequently, the present inventors successfully prepared a nanoparticle of beraprost sodium highly efficiently, although they failed in preparing a nanoparticle of epoprostenol, which is an early therapeutic agent used for pulmonary hypertension. The present inventors confirmed that the obtained nanoparticle excelled in sustained release of the beraprost sodium encapsulated in the particle and had the drug retantion in the blood, and therefore led to a continuous onset of a pharmacological effect, thereby accomplishing the present invention.