The present invention provides a micro-resonator including a plurality of waveguides forming optic junctions therebetween, with adjacent waveguides having different core permittivities and different cladding permittivities. Adjacent waveguides are mode-matched through adjustments of the core permittivities and the cladding permittivities of the waveguides to reduce or eliminate junction radiation, thereby providing high performance.

As is known in the art, high data rate optical fiber communication is achieved by subdividing the transmission spectrum of the fiber into many separate channels and then transmitting data rates compatible with electronic devices on each channel. This process is known as wavelength division multiplexing (WDM) and requires the use of optical filters, known as wavelength division multiplexers, in order to combine the lower data rate signals at the fiber input and to separate the data signals at the output. The current state of the art in WDM technology is what is commonly referred to as an arrayed waveguide grating (AWG). AWGs exhibit a competitive advantage over traditional thin film filters and bulk gratings since the AWGs are integrated on a chip, and are thus considerably smaller, more stable, and provide a greater degree of functionality.
In spite of the advantages listed above, AWGs have some limitations. Primarily, AWGs occupy large chip areas (>>10 cm2) and provide only moderate spectral efficiency. Integrated resonant devices such as ring resonators and photonic bandgap (PBG) or standing wave resonators occupy much smaller areas (<<10−3 cm2) and hold potential for greatly increased spectral efficiency. Resonators are essential optical devices for many other important optical components including lasers and nonlinear switches. A resonant cavity is characterized by its modal volume V and its quality factor Q where Q is a dimensionless lifetime, the time for the mode energy to decay by e−2π. Many useful devices require cavities that exhibit a very large Q and small volume V.
Three dimensional photonic bandgap (PBG) structures with singular defect sites have been shown to exhibit infinite quality factors while occupying small modal volumes. Similarly, the theoretical Qs of ring resonators can be very high. However, on account of the difficulty in fabricating the complicated geometries associated with three-dimensional PBG structures and ring resonators, considerable interest has been directed toward the simple one-dimensional case. Yet, upon reducing the dimensionality, PBG structures have been shown to radiate, which results in vastly diminished Qs, thereby limiting the devices' utility and effectiveness.
In view of the foregoing it would be desirable to provide integrated optic resonators that either minimize or totally eliminate radiation in one-dimensional PBG structures. It would be further desirable that the integrated optic resonators are manufacturable by planar fabrication techniques.


A light conversion member includes a surface of incidence which includes a recessed portion and on which a laser beam is incident and an output surface in which a wavelength of the laser beam is converted and the laser beam having the converted wavelength is output. The recessed portion has a shape corresponding to a wave front shape of the laser beam.

1. Field
The present application relates to a light conversion member and a lighting device including the same.
2. Background
A luminous element is a device which converts electricity into light. A light emitting diode (LED), a laser diode (LD), a laser and the like are representative luminous elements. As the demand for highly efficient low-power light sources has increased, active study on lasers, LDs and the high-power LEDs is in progress.
Generally, a highly efficient low-power light source emits excitation light having a wavelength of 500 nm or less, and the excitation light may be converted into visible light by a light conversion member such a phosphor and a quantum dot for use in a lighting device. However, some of the excitation light may be lost while incident on the light conversion member by Fresnel reflection of the surface of incidence.

Light conversion member and lighting device including the same


A fluid conduit has a longitudinal flow passage which includes a transverse cross section that is configured as a polygon, such as a convex or a concave polygon.

Prior art flow conduits typically comprise flow passages having circular cross sections. Such conduits are relatively simple to manufacture and are sufficiently strong for most applications. However, fluid conduits having circular flow passages are susceptible to erosion, especially when used to convey fluids at high velocities and/or containing abrasive particles.
The problem with erosion in fluid conduits having circular flow passages is particularly prevalent in pipe bends, such as pipe elbows. Pipe elbows of any angle are notorious for eroding in the presence of high velocity fluids containing abrasive particles such as sand, slurries or any other particles which are generated from upstream wear in the piping system or are introduced into the piping system in applications such as fracking, mining and coal and hydrocarbon transport. Pipe elbows are one of the main sources of erosion-related failures in fracking and hydrocarbon transport.
The prior art has attempted to solve the problem of erosion in pipe elbows by, among other approaches, modifying the geometry of the flow passage, which is typically round, to minimize the effects of erosion due to particles in the fluid impinging on the walls of the flow passage as the fluid changes direction. For example, the flow passage may be given an oval configuration with spiral round area changes. Other approaches to reducing erosion of pipe elbows have included adding baffles or deflectors to direct the flow away from the walls of the flow passage or coating the walls with various materials to better resist abrasive wear. Although these solutions help to reduce erosion, they are limited and short term. In addition, they reduce the flow area of the elbow, thus sacrificing elbow size and performance for less erosion.

Low erosion fluid conduit with sharp section geometry


In a nonvolatile semiconductor memory device, an interpoly dielectric film composed of a nitrogen-introduced CVD SiO2 film is used as the gate oxide films of MOS transistors in a low voltage region of a peripheral circuit region. Gate oxide films of MOS transistors in a high voltage region of the peripheral circuit region are composed of a laminate of the SiO2 film and a nitrogen-introduced CVD SiO2 film. This arrangement improves transistor characteristics and reliability of gate oxide films of the peripheral circuit MOS transistors. It is also possible to realize miniaturization and low voltage operation. Further, simplification of the production process is made possible.

Flash memory, which is a typical example of nonvolatile semiconductor memory device, is rapidly expanding its market as a memory unit for small-sized portable information devices such as cellular phones, digital still cameras, etc., as it is handy to carry, shock-proof and also capable of electrical bulk erasing on board.
This flash memory, as for instance illustrated in FIG. 18, usually consists of memory cells M which store data and MOS field effect transistors P constituting peripheral circuits for selecting the programming/erasing or read bits or generating a necessary voltage in the chips.
Unitary memory cell M comprises a set of MOS field effect transistors each consisting of a silicon (Si) substrate 201 having source and drain diffusion layers (not shown), a P well 204a formed on said Si substrate, a floating gate 207 and a control gate 209 both of which comprise mainly a polycrystalline Si film, an interpoly dielectric film 208 separating said gates 207 and 209, and a tunnel dielectric film 206 separating said floating gate 207 and P well 204a, and a plurality of such memory units are arranged as a matrix. As the interpoly dielectric film separating the floating and control gates of each memory cell, there is usually used a so-called ONO film which is a stacked film comprising a silicon nitride (Si3N4) film sandwiched between the SiO2 films, said ONO film being higher in permittivity and smaller in leakage current than the SiO2 film.
Peripheral circuit P consists of a combination of MOS field effect transistors each comprising a P well 204b and an N well 205 formed in an Si substrate 201, source and drain diffusion layers 212a and 212b, and a gate electrode 211 mainly comprising a polycrystalline Si film formed on the well with the interposition of a gate insulating film 210. Gate insulating film 210 usually comprises a SiO2 film formed by thermal oxidation method.
Each unitary memory cell M and peripheral circuit transistors P are usually separated by an isolation region 202 comprising a thick oxide film. The quantity of charge accumulated in the floating gate is controlled by biasing the positive or negative voltage generated by the peripheral circuit to the control gate 209, and the threshold voltage of the memory cell transistors is varied accordingly to thereby discriminate "0" and "1" of data.
However, increase of density of said nonvolatile semiconductor memory device has given rise to the new problems over the MOS transistors P for peripheral circuits and the memory cells M.
One of such problems is deterioration of characteristics and reliability of the MOS transistors for peripheral circuits due to degradation of the gate oxide film.
In flash memory, a high voltage, such as, for example, 18 V, is applied to the word line at writing/erasing. For the MOS transistors for peripheral circuits exposed to such high voltage, the gate oxide film thickness is increased to, for instance, around 25 nm so that the film can withstand such high voltage. However, in case the shallow groove isolation method is applied in place of the conventional selective oxidation method (LOCOS) for isolation between the peripheral MOS transistors for the purpose of miniaturization of the elements, if the thick (such as 25 nm) gate oxide film is formed by the thermal oxidation method, there arises a situation in which the thickness of the gate oxide film adjacent to the shallow groove isolation region becomes excessively small in comparison with the active region. This gives rise to some serious problems such as "kink" of current-voltage characteristics of the MOS transistors and lowering of breakdown voltage of the gate oxide film.
The second problem is difficulty in thinning of the interpoly dielectric film of the memory cells M which is essential for the reduction of programming voltage.
The voltage Vfg applied to the floating gate for the programming/erasing operation of the flash memory is given by the following equation:Vfg=C2·Vcg/(C1+C2)  (1)wherein Vcg is voltage applied to the control gate, and C1 and C2 are capacitance of the tunnel dielectric film and the interpoly dielectric film, respectively. In order to transfer the voltage applied to the control gate efficiently to the floating gate to reduce the programming voltage, it is effective to increase C2, namely to make thinner the interpoly dielectric film. However, in the case of the "ONO film", i.e. a stacked film comprising a silicon nitride (Si3N4) film sandwiched between the SiO2 films, which has been widely used in the art, if the thickness of the SiO2 film on each side of the laminate is made 5 nm or less, there would arise the problem that the charge accumulated in the floating gate might leak out to the control gate, that is, actualization of so-called retention degradation. Also, when the SiO2 film on the upper side of the laminate is made 5 nm in thickness, it is necessary to deposit the Si3N4 film to a thickness of around 10 nm or greater for preventing oxidation of the polycrystalline Si layer on the lower side. Thus, the limit of possible reduction of thickness of the ONO film was around 15 nm in terms of effective oxide thickness.
JP-A-10-242310 discloses a technique for reducing the programming voltage by lessening the film thickness by applying a nitrogen-introduced single-layer CVD SiO2 film as the interpoly dielectric film in place of the conventional ONO film.
However, when the gate oxide film of the peripheral circuit MOS transistors was formed by the thermal oxidation method after forming the interpoly dielectric film, as commonly practiced in manufacture of the conventional flash memories, there would arise the problem that the highly doped floating gate polycrystalline Si be oxidized thickly because the single-layer CVD SiO2 film has no oxidation resistance unlike the ONO film. Therefore, development of a reliable method for forming a gate oxide film of the peripheral circuit MOS transistors when using a single-layer CVD SiO2 film as the interpoly dielectric film for memory cell was essential.
The third problem is the increase of the number of the steps in the production process.
In the conventional flash memory production process, the tunnel dielectric film 206 of memory cells, their interpoly dielectric film 208 and the gate insulating film 210 of peripheral circuit MOS transistors have been formed severally in succession, so that the process involved many steps and this has been an obstacle to the effort for cost reduction. Recently, an idea of the techniques for making two type thickness of the gate oxide film of MOS transistors in the peripheral circuit region is proposed for attaining further enhancement of programming/erasing speed and read speed of the flash memory. It is considered that the simplification of the flash memory production process will become an important subject for study in the art.
The above-said three problems are closely associated with each other from the viewpoint of formation of interpoly dielectric films of memory cells and gate oxide film of peripheral circuit MOS transistors, and for the solution of these problems, the development of a novel nonvolatile semiconductor memory device and its production process has been required.
Accordingly, an object of the present invention is to make highly reliable the gate oxide film of peripheral circuit MOS transistors of nonvolatile semiconductor memory device and to improve its transistor characteristics.
Another object of the present invention is to provide a process for forming the interpoly dielectric film and the gate oxide film of MOS transistors in the peripheral circuit region that accord with the miniaturization and low-voltage operation of nonvolatile semiconductor memory device.
Still another object of the present invention is to simplify the production process of nonvolatile semiconductor memory device.

Nonvolatile semiconductor memory device with improved gate oxide film arrangement


An assembly for transferring current comprises at least one electrically conductive slip ring; at least one electrically conductive brush for supplying current to the at least one slip ring; and an electric or pressure actuator driven vibration source for changing the position of the brush with respect to the slip ring. If desired, brush current can shared by using inductance variations or by selective coupling of rotor windings to the slip rings.

The invention relates generally to high power machines and more particularly to slip ring brush systems.
In high power, variable speed machines such as described by commonly assigned Runkle et al., U.S. Pat. No. 5,742,515, rotors are excited through electrically conductive slip ring assemblies. Conventional slip ring and brush assemblies transfer power at low voltage, moderate current levels and relatively high speeds. It would be useful to have assemblies that can accommodate thousands of amperes even when rotating at low speeds (about zero (0) to about one hundred (100) rotations per minute). In conventional slip ring and brush assemblies, rotating at low speeds may lead to localized overheating, marking, and deformation.
U.S. Pat. No. 1,157,885 of the London Patent Office to Brown, Boveri and Co. Ltd. describes a technique for xe2x80x9ccausing the brushes to be moved back and forthxe2x80x9d by xe2x80x9cusing a device which serves to produce a periodic rotary motion of those parts of the machine on which the brushes are mounted.xe2x80x9d To accomplish this motion, xe2x80x9cbrush bridges are connected with the output shaft of a differential gear that changes their position, and an input shaft to this gear is equipped with means for altering the central position of the brush bridge, a second input shaft to this gear being provided with means for effecting a periodic back and forth rotation with variable amplitude.xe2x80x9d Azimuthal motion is thus achieved. The resulting assembly of this technique is difficult to control and to run at high voltages.
xe2x80x9cRotary Converters,xe2x80x9d Westinghouse Electric and Manufacturing Co., Circular No. 1028, Apr. 1903, describes an embodiment wherein axial motion is achieved between brushes and a commutator on a rotor shaft by moving the entire rotor axially in an oscillatory manner. Moving the entire rotor shaft is awkward, may be harmful, requires significant power, and can limit the amplitude of motion.
Other limitations of variable high speed machines relate to the non-uniform current distribution through the brushes that contact the slip rings as well as the rotor winding leads that couple rotor windings to slip rings. Because the brushes typically are coupled by a common, single electrically conductive lead, the current varies between brushes depending upon the proximity to the conductive lead. Rotor windings are also coupled together prior to attachment to the slip rings and similar current variations result. Although stators are sometimes connected to stationary connection rings with separate leads, as shown in Lawrence, Principles of Alternating-Current Machinery, 4th Ed., McGraw-Hill Book Co. 1953, such configurations are not used for slip rings of wound rotor machines.
Thus, there is a need for a reliable, low loss slip ring brush assembly that can efficiently accommodate a high level of current and voltage and a low rotation speed without gears. It would additionally be advantageous to have a slip ring brush assembly with uniform current sharing capabilities across the brushes and slip ring.
In accordance with one embodiment of the present invention, a brush for a slip ring is actuated with an electric or pressure actuator acting as an auxiliary driver to provide relative motion between the brush and the slip ring.
In accordance with another embodiment of the present invention, current is shared by using inductance variations or by selective coupling of rotor windings to the slip rings.


An apparatus and a method for reallocating segments in a broadband wireless communication system are provided. An average density for all cells in system and an average minimal inter-cell distance R are computed. A circle is determined having a radius kR and a center at a corresponding cell by increasing a constant k until a density of the circle becomes less than or equal to the average density. A cluster is generated for each cell, which is composed of cells included in the determined circle. Accordingly, segment allocation capability can be improved while minimizing a width of segment reallocation.

1. Field of the Invention
The present invention relates generally to segment reallocation, and more particularly, to an apparatus and method for reallocating segments in a broadband wireless communication system.
2. Description of the Related Art
An Institute of Electrical and Electronics Engineers (IEEE) 802.16e system employs a cellular scheme and supports a frequency reuse factor of 1. As a result, neighboring cells can use the same frequency. Thus, a Mobile Station (MS) existing in such a system has to be able to distinguish a Base Station (BS) where the MS resides, from a neighboring BS among a plurality of BSs, which use the same frequency. For this purpose, whenever a frame is transmitted to the MS, each BS transmits the frame by inserting a Pseudo Noise (PN) code to a preamble, which is a first symbol of the frame.
According to an IEEE 802.16e standard, a total of 114 preamble PN codes are defined, and the codes have code indices 0 to 113, respectively. In addition, the preamble PN codes each have an Identification (ID) cell (hereinafter, referred to as IDcell) and a segment number. By analyzing the preamble PN codes, the MS can recognize a code index, an IDcell, and a segment number of a corresponding BS. The IDcell has 32 values (i.e., 0 to 31). The segment number has three values (i.e., 0 to 2). Not all codes have unique IDcell and segment number combinations. Thus, among the 114 codes, only the codes 0 to 95 have unique IDcell and segment number combinations. The IDcell and segment number combination of the codes 96 to 113 are duplicated with that of the codes 0 to 95.
A segment is used for various purposes, and a result of segment allocation has a significant effect on system performance. The segment determines a carrier set through which a preamble is transmitted. The preamble is transmitted through only a ⅓ part of a sub-carrier, which remains after removing a guard band. The sub-carrier set may be determined by using Equation (1) below.carrier set=segment+3k (k=0, 1, 2, . . . )  Equation (1)
Equation (1) shows that, when the same segment is allocated to neighboring sectors, preambles of two sectors are transmitted through the same carrier set. In this case, even if an MS can obtain a preamble without any problems because different code indices are allocated to the preambles of the two sectors, downlink throughput may deteriorate.
In a downlink channel, the MS estimates a pilot signal transmitted from a BS. The estimation result is used in a demodulation process. However, similar to a Frame Control Header (FCH) and a Downlink-MAP (DL-MAP), when information is transmitted during first few symbols of a frame, no pilot signal is transmitted from the BS, resulting in difficulty in channel estimation. Therefore, the MS estimates a channel by using the preamble. In this case, whether a carrier set is duplicated between neighboring sectors significantly affects capability of channel estimation. If different segments are allocated to neighboring sectors and thus preambles are transmitted through different carrier sets, then channel estimation can be accurately achieved through the preamble, which leads to improved modulation capability of the FCH and the DL-MAP. On the other hand, if the same segment is allocated to the neighboring sectors, channel estimation is inaccurately achieved through the preamble, which may result in deterioration in downlink demodulation capability.
Moreover, a segment may determine a frequency band used in a downlink Partial Usage of Sub-Carrier (PUSC) zone. In the downlink PUSC zone, a sub-carrier is divided into 6 groups, which include 3 major groups and 3 minor groups. Each sector may use all or some of the 6 groups, and information thereof is transmitted to the MS through the FCH. In this case, each sector must use one or more major groups, and the number of major groups to be used is determined by a segment allocated to the sector. In order to reduce interference between cells in a cell boundary area, the system may allow some groups to be used between sectors, and this will be referred to as segmented PUSC. If the neighboring sectors use the same segment, the two sectors use the same group. As a result, interference is not diminished even when the segmented PUSC is used, which leads to deterioration in downlink throughput.
As such, when the same segment is allocated to neighboring sectors, downlink modulation capability may deteriorate. Therefore, segment allocation may significantly affect system performance. However, since the number of segments is limited to three, it is not easy to allocate segments while minimizing segment duplication between the neighboring sectors.
Even when segments are effectively allocated, the segments may have to be reallocated later in some cases. For example, existing segment allocation may no longer be useful when there are changes in radio configurations such as locations of some BSs within a system, transmission power, an antenna angle, an antenna type, etc. Furthermore, the existing segment allocation may not be preferable when a radio-wave environment changes due to alternation of buildings and topographies. If this is the case, segment reallocation is needed. The segment reallocation may be carried out by allocating new segments to all sectors in the system according to a conventional algorithm. However, when changes are significant in new segment allocation, this may affect operations of the system.
Accordingly, there is a need for a segment reallocation method in which, if required, segments are reallocated by using a result of existing segment allocation, so as to improve segment allocation capability while minimizing changes in segment allocation.

Apparatus and method for reallocating segments in broadband wireless communication system

Korea Advanced Institute of Science and Technology


A memory module implementing a desired memory capacity by use of a plurality of memory chips. The memory module has a fault bit substituting device that compensates for fault bits detected in any of the memory chips. This improves the yield of the memory module and lowers the production costs thereof without recourse to expensive equipment such as wafer processors.

1. Field of the Invention
The present invention relates to a memory module that realizes a desired memory capacity using a plurality of memory chips. More particularly, the invention relates to a memory module offering a high yield and reduced costs, a method for control of that memory module, and a method for setting a fault bit table for use with that memory module.
2. Prior Art
Memory chips made of semiconductor integrated circuits are known to develop fault bits for diverse reasons during their production process.
The presence of fault bits is circumvented conventionally by equipping individual memory chips with redundant circuits. To compensate for the fault bits, a laser trimming machine commonly called a wafer processor is used at wafer die sort time to cut polycrystal Si or Al parts by laser melting and to connect polycrystal Si parts for conduction by later annealing while each memory chip is being tested.
One disadvantage of the above prior art measure is that wafer processors are very expensive (they often cost a few hundred million yen per unit).
Another disadvantage of the prior art is a poor throughput due to the fact that the fault bits are compensated while the addresses of each memory chip are being tested sequentially. In the case of a one-megabit DRAM (dynamic random access memory), it typically takes several minutes to compensate for the fault addresses of each chip by wafer processor.
Most memories are supplied and used in the form of memory modules (including memory boards and memory cards). Conventionally, memory modules are each composed of the necessary number of fault-free chips. One defective memory chip within a module means a totally disabled address area of that memory chip. In many cases, the module containing even one defective chip is discarded in total as useless. Therefore usually the memory module consists of only good chips.
A solution to the above problem of one chip disabling the entire module is disclosed by Japanese Patent Laid Open No. 61-180350. The disclosure involves adding at least one reserve memory chip to the memory module so that if a memory chip therein malfunctions, the defective chip is replaced by a reserve chip. The setup is called a field programmable logic array (FPLA).
Another solution to the problem above is disclosed by Japanese Patent Laid-Open No. 3-191450. The disclosure proposes furnishing a plurality of memory chips including at least one reserve chip amounting to N chips that constitute the memory module. In operation, only n chips (n<N) are used. If a faulty chip develops among the operating chips, that faulty chip is replaced by one of the remaining fault-free chips (N-n).
Both of the above solutions involve replacing each faulty chip with one good memory chip. Considering the fact that even a faulty memory chip contains numerous parts that are still good, the waste involved is enormous. Needless to say, all memory chips replacing the defective must be entirely fault-free chips.

Memory module, method for control thereof and method for setting fault bit table for use therewith


An x-ray confocal defect detection system comprises an x-ray source, a confocal component, and defect detectors and operates on a target portion of a semiconductor device. The x-ray source generates x-ray energy. The semiconductor device includes a plurality of formed layers. The target portion is a selected layer or portion of the plurality of formed layers. At least a portion of the x-ray is transmitted through the semiconductor device as transmitted x-ray. The confocal component receives the transmitted x-ray and passes target x-ray intensity from the target portion of the transmitted x-ray energy. Detectors receive the target x-ray from the confocal component from which defect analysis can be performed.

Semiconductor fabrication faces shrinking device dimensions and increasing process complexity. Devices of today are smaller and require more fabrication processes than devices of even a few years ago. Additionally, the shrinking dimensions require ever tighter tolerances for performance of the process employed in semiconductor fabrication.
Semiconductor manufacturers generally recoup their manufacturing costs by selling their fabricated semiconductor devices. However, some semiconductor devices fail to meet operational requirements and are, therefore, unable to be sold. As a result, the manufacture does not recoup the manufacturing costs for the failed devices.
A critical statistic in semiconductor fabrication is yield, which is a percentage of devices fabricated that meet operational requirements. A goal of device fabrication process is to reach 100 percent yield, although this goal is not generally obtained. However, the closer to this goal and the higher the yield, the greater the profitability for the manufacturer.
Semiconductor fabrication processes and the devices themselves are very sensitive to out of tolerance process conditions, mishandling, movement, temperature, humidity, and the like. As a result, defects in structures and layers present in semiconductor devices can occur.
An important step in the manufacture of integrated circuits is the formation of metal conductors, which provide electrical connections to devices formed therein. Conductors in integrated circuits are typically formed of copper metallization, in order to take advantage of the lower resistance of copper (though aluminum is also used in certain cases). The minimum line width is sought to be minimized, since it is often a factor upon which the overall integrated circuit chip area depends. In order to minimize the chip area required for realization of complex integrated circuits such as digital signal processors (DSPs) or microprocessors, multiple metallization levels are common in the art, despite the complex manufacturing processing required for their fabrication.
Voiding in metal conductors is an important defect that can occur in the fabrication of thin, closely-spaced, metal conductors, particularly in multiple layers. Voids may be caused in the deposition of the metal film, as a result of metal etch, or by unintended corrosion during processing. Voids can also be caused by migration of atoms during thermal processing under stress fields that develop over the metal line, or due to electrical currents; voids in metal conductors can also be present because of the inability of large grains to fill gaps, particularly in small geometries and over topography. Because of the yield loss due to defective metal lines, and also considering later-life reliability hazards resulting from the void, the prevention and/or mitigation of voids in metal conductors is important in modern integrated circuit manufacturing.
In previous years with larger devices, metal voids could be readily detected by optical inspection (automated or otherwise) of the integrated circuits during or after their manufacture. Additionally, the reduction in metal conductors to the sub-micron range has not only reduced the optical visibility of the conductors, but also reduced the minimum size of a killing void further below the visibility of optical microscopy. In addition, the presence of voids within the body of a conductor line generally cannot be detected by visual or scanning electron microscopy (SEM) techniques that are currently in use. Particularly in damascene copper structures, voids are sometimes buried, and are thus optically invisible, regardless of the conductor dimensions. The implementation of multiple metal levels has also limited optical inspection, because the 'noise' introduced by the grains in the underlying metal level reduces the efficacy of automated inspection of the top-most metal at any particular point in the fabrication sequence.
As a result, at least some conventional void detection relies upon destructive techniques. Typically, sample wafers from the manufacturing line are cross-sectioned, and the cross-sections are examined by SEM for a measure of the metal film quality. The destructive nature of this inspection reduces the number of samples that may be inspected by SEM. Furthermore, the nature of SEM precludes the viewing of more than a small number of locations of the wafer within each sample. The preparation of the cross-sectional samples for SEM analysis is also time-consuming, and thus costly. As such, routine SEM inspection is not a very effective, feasible measure of the metallization film quality.
Some other techniques are currently being developed for measuring the quality of metallization films. Magnetic force microscopy measures variations in magnetic flux caused by voids in the metallization; of course, this measurement not only requires current to be conducted through the conductor during measurement, but also highly precise magnetic field detection elements. Surface acoustic wave (SAW) microscopy has also been proposed, in which variations in reflection of acoustic waves due to voids may be measured, but resolution considerations tend to limit the applicability of SAW microscopy to small geometries. Additionally, some of the proposed methods utilizing SAW microscopy essentially rely upon 'golden' structures that are void-free but otherwise identical to the conductor structure being inspected, which is an onerous stipulation.

X-ray confocal defect detection systems and methods


A device, such as a safety support, comprising a body and a base, in which the base comprises at least one zone of resistance which is essentially circumferentially inextensible and is mechanically coupled to the body, and at least one centering zone which is mechanically joined to the resistance zone by connections with low tensile rigidity and so to be mechanically uncoupled from the body.

1. Technical Field of the Invention
The present invention concerns devices intended to fit around a wheel rim, such as safety supports for vehicle tires, sensors, or automatic inflation systems and, more particularly, to the connection between such devices and the rims around which they are mounted.
2. The Related Art
The main function of tire safety supports is to support the load in the event that the tire suffers a major pressure loss. When tires are inflated normally, the safety supports must not have any adverse effect on the dynamic properties of the tire. In particular, they must remain well centered around the rim; that is to say, the rotational axes of the safety support and of the rim must remain one and the same to avoid any out-of-balance effect, and this, whatever the temperature of the support and the vehicle's rolling speed. It must also be possible to mount the safety supports around the wheel rims of vehicles and take them off again in an easy way, i.e., using limited forces which make it possible to fit and remove them by hand.
U.S. Pat. No. 5,690,762 discloses a safety support made of an elastic material designed to be fitted on the wheel rim of a touring vehicle, the rim being of the usual, drop-center type. This support comprises a body with a crown designed to come into contact with the crown of the tire if the latter should lose pressure, and a base designed to come into contact with the rim. This support also comprises annular reinforcement elements oriented circumferentially and essentially inextensible, whose diameter is slightly larger than the diameter of the rim hooks for which the support is provided. The base consists of two annular zones whose inside diameter in the free state is smaller than that of the parts of the rim upon which they are to rest: the compression of these annular zones therefore ensures good centering of the support on the rim. The function of the annular reinforcing elements is, in particular, to prevent the annular zones of the base from extending under the action of centrifugal forces at high speed until contact with the rim is lost.
When a safety support is intended to be fitted to a two-part rim or a rim having a bearing surface for a support whose diameter is larger than that of one of the rim hooks as shown in FIG. 1, the annular reinforcing elements can be arranged in the base. This is so in the case of the support disclosed by U.S. Pat. No. 5,891,279. Such a position of the annular reinforcing elements facilitates the construction of the support.
For such a support, bearing in mind the manufacturing tolerances of the rim and the support itself, it is no longer possible to arrange annular zones radially on the inside whose compression will ensure good centering around the rim regardless of the speed while also ensuring easy fitting and removal.

Device designed to be fitted around a wheel rim and comprising centering means


A liquid droplet discharge apparatus includes a conveyor belt that retains and conveys a recording medium, a liquid droplet discharge head that discharges liquid droplets onto the recording medium retained on the conveyor belt, a discharge belt that moves to a recording medium feeding position of the conveyor belt, receives the recording medium, and retains and conveys the recording medium to a discharge port; and an inversion belt that moves to the recording medium feeding position, receives and retains the recording medium, and feeds the recording medium to an inversion path. By disposing the inversion belt, the conveyance direction of the recording medium can be switched without contacting the recording surface of the recording medium, and even when two-sided printing is to be conducted at a high speed, the inversion belt does not become soiled by the liquid droplets adhering to the recording surface of the recording medium.

1. Field of the Invention
The present invention relates to a liquid droplet discharge apparatus applied to image recording apparatus or the like which record images by discharging ink droplets from a recording head onto a recording medium that is retained and conveyed by a conveyor belt.
2. Description of the Related Art
In image recording apparatus of the inkjet format which record an image on paper by discharging ink from a recording head, a printing format called serial scanning, in which printing is conducted one line at a time by reciprocally moving the recording head in the direction orthogonal to the conveyance direction of the paper while conveying the paper, is widely used mainly for personal use.
Further, in recent years, image recording apparatus of the so-called full-line head format have become commercially available. Here, a non-scanning-type recording head is used which corresponds to the width of the paper and includes numerous nozzles that are arranged along the direction (width direction) orthogonal to the conveyance direction of the paper. An image is recorded while the paper is continuously conveyed, whereby the printing speed is improved, and office use can also be accommodated.
Incidentally, in two-sided printing mechanisms using such inkjet recording technology, when printing is conducted on one side of the paper, the ink on that side does not dry immediately thereafter, and when printing is to be conducted on the other side of the paper, conventionally printing on the other side of the paper is conducted after the ink on the one side of the paper dries. For this reason, different actions have been taken, such as setting the drying time and speeding up drying by lowering the printing density on the surface of the paper, but there have been instances where these actions have led to a decline in productivity and a decline in image quality.
For this reason, in Japanese Patent Application Publication (JP-A) No. 2001-287873, a configuration is described where an inversion standby position is disposed at a position that does not interfere with a sheet of paper following a prior sheet of paper for which one-sided printing has ended. The switching of the conveyance path is done with a branch pawl, and in recording apparatus that conduct two-sided printing at a high speed, the undried ink may contact with the branch pawl or the conveyance path and soiling of the conveyance roll pairs can arise.

Liquid droplet discharge apparatus including duplex recording medium transport unit


Embodiments of the disclosure relate to compositions of isolated nucleic acid sequences, methods, workflows and kits of use thereof for detection of Salmonella enterica, subspecies enterica, serovar Enteritidis (S. Enteritidis) in a sample, particularly in a food (egg, poultry) or environmental sample (including poultry-related environmental samples). Embodiments of the disclosure may also be used to differentially detect S. Enteritidis without cross-reacting with S. Paratyphi C or other closely related Salmonella species. In some embodiments, methods and kits of the disclosure may comprise a TaqMan® assay. Following sample enrichment, methods of detection may be completed in approximately 3 hours.

Salmonellosis (Salmonella infection) has been linked to the pathogen Salmonella enterica subspecies enterica serovar Enteritidis (S. Enteritidis). Poultry products, including eggs and poultry birds, serve as a reservoir for S. Enteritidis (SE). Poultry birds are often asymptomatic for Salmonella infection and hence the pathogen is difficult to detect. The pandemic of S. Enteritidis is believed to have started in the mid 1980s by interaction of the pathogen with poultry environment, especially hen house conditions, poultry birds, eggs as well as the human hosts who consume poultry products. The S. Enteritidis pathogen can pass to humans via contaminated poultry products through the food production chain. Several outbreaks have been reported where eggs were the source of human infection. Undercooked or raw eggs and poultry meat constitute a high risk of infection for humans. Two strains of Salmonella, both S. Typhimurium and S. Enteritidis, have been shown to infect chicken reproductive tracts and contaminate forming eggs but S. Enteritidis persists even after eggs are laid.
Starting Jul. 9, 2010, the US Food and Drug Administration (FDA) published new regulations that require commercial egg producers to test poultry houses and egg samples for the presence of S. Enteritidis. Since the levels are often low and sporadic, highly sensitive detection methods are required for robust and reliable detection of the pathogen.
A sensitive and specific detection method for the presence of S. Enteritidis is needed for the testing of humans, eggs, hens and other poultry-related samples.


An air bag cover assembly including a cover element of generally profiled configuration and including one or more mounting posts extending downwardly from the interior surface of the cover element. A reaction plate of generally curved surface contour substantially matching the contour of the inner surface of the cover element is held in place at a position below the cover element. A membrane horn switch is disposed in sandwiched relation between the reaction plate and the cover element. The matching contour of the inner surface of the cover element and the reaction plate establishes a substantially uniform operative separation between the cover element and the membrane horn switch.

The present invention relates to a cover assembly for a vehicle air bag, and more particularly to a cover assembly for use at the interior of a steering wheel on the driver""s side of a vehicle which incorporates a contoured cover element, an underlying membrane horn switch and a contoured reaction plate beneath the membrane horn switch. The reaction plate includes an upper surface contoured to substantially match the interior contour of the cover element such that a substantially uniform distance is maintained between the cover element and the horn switch between the upper and lower edges of the cover element.
It is well known in motor vehicles to provide an air bag module for protecting a vehicle occupant. It is also generally known to provide an air bag module including an inflatable restraint cushion and an inflator for discharging inflation gas to inflate the cushion upon sensing predetermined vehicle conditions such as deceleration exceeding a certain level. It is also known to provide air bag modules including pressure activated membrane horn switches disposed in sandwiching relationship between a molded depressable cover element and a substantially rigid reaction plate. Such air bag modules are illustrated and described in U.S. Pat. No. 6,236,309 to Haag and U.S. Pat. No. 5,762,365 to Worrell et al. the contents of which are incorporated by reference as if fully set forth herein.
The membrane horn switches conventionally comprise two very thin sheets having conductive coatings which are normally separated by thin spaces. Pressure on the switch forces the conductive surfaces together so as to complete a circuit and thereby actuate the horn. Typically, membrane horn switches are less than about one millimeter in thickness. To actuate the horn, the driver must sufficiently compress the cover member so as to apply the requisite pressure to the membrane horn switch to bring the opposing conducting surfaces together.
The use of a reaction plate in mounted relation to the cover element generally below the membrane horn switch provides a substantially solid surface against which the membrane horn switch can be compressed to actuate the horn. In practice, the reaction plate is typically held in place below the cover element and the membrane horn switch by a plurality of mounting posts which extend away from the interior surface of the cover element through aligned apertures in both the membrane horn switch and the reaction plate. The ends of the posts are melted together to heat stake the reaction plate to the cover. The interior surface of the cover element may also incorporate horn actuating projections which normally extend partially across the space between the interior surface of the cover element and the membrane horn switch. The use of such horn actuating projections reduces the distance the cover element must be compressed in order to actuate the membrane horn switch.
In the past, the reaction plates utilized have been of a generally planar configuration thereby forming a generally flat surface in operative opposing relationship to the interior surface of the cover element. While such a planar surface provides substantially uniform support to the membrane horn switch, the distance between the membrane horn switch and the interior surface of the cover element may vary across the module if the interior surface of the cover element is not also planar.
Recently, cover elements have become more stylized leading to a greater degree of curvature in the outer surface of the cover element facing the occupant. In addition, the use of so called xe2x80x9csingle shotxe2x80x9d injection molding procedures to form the cover elements from a single layer of material has gained popularity. In such xe2x80x9csingle shotxe2x80x9d constructions it is generally desired for the cover element to have a substantially uniform thickness in the regions overlying the, membrane horn switch so as to promote substantially uniform compressibility in those regions. However, in a contoured construction the incorporation of a substantially uniform thickness gives rise to a corresponding contour across the inner surface of the cover element. Such an inner surface contour gives rise to a variation in the distance between the interior surface of the cover element and the membrane horn switch. This differential distance may require the cover element to be depressed to a greater extent in some locations in order to contact and actuate the membrane horn switch.
The present invention provides advantages and alternatives over the prior art by providing an air bag cover assembly including a cover element of generally profiled configuration and including one or more mounting posts extending downwardly from the interior surface of the cover element. A reaction plate of generally contoured construction substantially matching the contour of the cover element is held in place at a position below the inner surface of the cover element. A membrane horn switch is disposed in sandwiched relation between the reaction plate and the inner surface of the cover element.
According to one aspect of the present invention, an air bag cover assembly is provided including a cover element having a curved exterior show surface and a curved interior surface and wherein a plurality of mounting posts extend downwardly away from the interior surface. A reaction plate of substantially curved contour substantially matching the contour of the inner surface of the cover element is held in place at a position below the inner surface of the cover element by heat staking of the mounting posts. A membrane horn switch is captured between the reaction plate and the interior surface of the cover element such that the distance between the interior surface of the cover element and the membrane horn switch is substantially uniform across the cover assembly.
According to another aspect of the present invention, the reaction plate includes a plurality of apertures for acceptance of mounting posts therethrough. The mounting posts preferably include a shoulder portion which engages a substantially planar shoulder stop in surrounding relation to the post acceptance apertures at the upper surface of the reaction plate. A plurality of protuberant boss elements are disposed across the underside of the reaction plate substantially at the post accepting apertures to facilitate heat staking at those locations. Preferably, the reaction plate is curved in an arched configuration substantially between the forward and aft edges adjacent the upper and lower edges of the air bag module.
The construction according to the present invention is believed to promote an enhanced degree of uniformity in the force required to actuate the membrane horn switch at various locations beneath a curved cover while at the same time facilitating proper alignment and attachment of the component parts thereby improving the manufacturing process. Accordingly, the present intention is believed to provide a useful advancement over the prior art.

Air bag cover assembly with curved horn reaction plate


The invention provides novel glycosaminoglycan derivatives having a repeating unit structure of two saccharides of hexosamine and hexuronic acid as a backbone structure, in which the bonds between 2- and 3-positions carbon atoms of hexuronic acid as its constituting monosaccharide are partially cleaved and a part or all of the 2-position hydroxyl groups of uncleaved hexuronic acid are not substituted with a sulfate group, which has low anticoagulation activity and excellent neurite outgrowth promotion accelerating activity and sialidase inhibition activity; a process for producing the glycosaminoglycan derivatives, comprising a cleavage treatment of the bond between the 2- and 3-position carbon atoms of hexuronic acid having no sulfate group at the 2-position of glycosaminoglycan, and a selective desulfation treatment of the 2-position sulfate group of hexuronic acid; and a pharmaceutical composition comprising the glycosaminoglycan derivative as an active ingredient.

The present invention relates to novel glycosaminoglycan derivatives having a neurite outgrowth promoting activity and a sialidase inhibiting activity, a process for producing them, and a pharmaceutical composition containing the glycosaminoglycan derivative as an active ingredient.
Neuronal disease is generated by the growth-inhibition of neural cells, by the induction of neural cell necrosis caused by the inability of the cells to be maintained due to reduction of sugar supply or energy metabolism inhibition in the cells as a result of ischemia, or by the inhibition of neurotransmission due to degradation of neurotransmitter. Accordingly, the treatment of this disease has been made with the aim of maintaining growth of neural cells, preventing ischemia of neural cells, or maintaining energy metabolism in the neural cells. That is, it is considered that the fundamental measures for the neuronal disease are to administer neurotrophic factors as substances having a neural cell growth activity (e.g., nerve growth factor: NGF, brain-derived neurotrophic factor: BDNF, ciliary neurotrophic factor: CNTF, fibroblast growth factor: FGF etc.) from the outside or promote synthesis of the neurotrophic factors, to prevent ischemia of neural cells and reduction of energy metabolism in neural cells caused by excess production of sorbitol formed by the activity of aldose reductase, by applying an aldose reductase inhibitor, and to maintain transmission of neural cells by preventing degradation of acetylcholine through the administration of an acetylcholine esterase. However, there are problems, such as antigenicity due to purity of the substance to be administered, side effects caused by the inhibition of enzyme activity, toxicity of the substance per se to be administered, and the like.
Also, it is known that glycosaminoglycan has the activity to accelerate neurite outgrowth promotion(J. Cell Physiol., 135: 293-300 (1988)). Furthermore, it is known that heparin and derivatives thereof, periodate oxidation reduction heparin and per-sulfated heparin, have a neurite outgrowth promoting activity and are effective in treating traumatic, ischemic and toxic neuropathy (JP-A-6-157322), but substances having a sufficient activity to inhibit these diseases for applying to medicaments have not been obtained yet.
On the other hand, it is known that sialidase (neuraminidase) inhibitors, such as GS4104 (WO 96/26933), zanamivir (4-guanidino-Neu4Ac2en: WO 91/16320, WO 94/07885), and the like, are effective as antiviral agents, particularly as influenza treating agents.
Since heparin and derivatives thereof are biological substances, they have a low antigenicity, but their use and concentration in using as medicaments are considerably limited due to their high anticoagulation activity. Generally, when heparin is administered to the living body, bleeding activity due to the high anticoagulation activity becomes a serious problem. Accordingly, a new substance having a low anticoagulation activity and a reinforced neuropathy improving effect is expected.
In order to resolve these problems, the present inventors have conducted intensive studies with the aim of obtaining a substance having a low anticoagulation activity for blood and an excellent neuropathy improving effect, and found, as a result of the efforts, that glycosaminoglycan derivatives having a specified structure have a high neurite outgrowth promoting activity, namely a neuropathy improving activity, and have accomplished the present invention by confirming that the anticoagulation activity of this substance is more sharply reduced than heparin. That is, it was found that novel glycosaminoglycan derivatives having a repeating unit structure of two saccharides of hexosamine and hexuronic acid as the backbone structure, in which the bondage between the 2- and 3-position carbon atoms of hexuronic acid as its constituting monosaccharide is partially cleaved and at least a part of the uncleaved hexuronic acid has no sulfate group on its 2-position, has a low anticoagulation activity and an excellent neurite outgrowth promoting activity. A pharmaceutical composition having an excellent effect for improving neuropathy using these properties can be provided. Additionally, based on the fact that a sialidase activity is increased and ganglioside known to have a relation to the maintenance and acceleration of a neurotrophic factor activity on the cell membrane is reduced when cell death and involution of neurite occur, the present inventors have conducted further investigations and found that the novel glycosaminoglycan derivative has a strong sialidase inhibition activity to provide a sialidase inhibitor using this inhibition activity of the glycosaminoglycan derivatives.
The first embodiment of the present invention relates to novel glycosaminoglycan derivatives having the following properties (a), (b) and (c) and comprising at least one structure represented by general formula (1) described in (d) per molecule of a backbone structure formed by a repeating unit structure of hexosamine and hexuronic acid:
(a) mol % of 2-deoxy-2-sulfamino-4-O-(4-deoxy-2-O-sulfo-xcex1-L-threo-hex-4-enopyranosyluronic acid)-6-O-sulfo-D-glucose (hereinafter also referred to as xe2x80x9cxcex94DiHS-tri(U,6,N)Sxe2x80x9d) being from 0 to 10%, mol % of 2-deoxy-2-sulfamino-4-O-(4-deoxy-xcex1-L-threo-hex-4-enopyranosyluronic acid)-6-O-sulfo-D-glucose (hereinafter also referred to as xe2x80x9cxcex94DiHS-di(6,N)Sxe2x80x9d) being from 95 to 70%, and mol % of 2-deoxy-2-sulfamino-4-O-(4-deoxy-xcex1-L-threo-hex-4-enopyranosyluronic acid)-D-glucose (hereinafter also referred to as xe2x80x9cxcex94DiHS-NSxe2x80x9d) being from 5 to 20%, in a disaccharide composition obtained by a disaccharide analysis through a combination of degradation by a glycosaminoglycan degradation enzyme with analysis by high performance liquid chromatography,
(b) activated partial thromboplastin time (APTT) when measured by adding to standard blood plasma at a final concentration of 3 xcexcg/ml being 50 seconds or less,
(c) weight average molecular weight being from 9,000 to 13,000 Da (dalton), and
(d) general formula (1):
(wherein R1represents H or SO3H; and R2 represents COCH3 or SO3H).
The second embodiment of the present invention relates to a process for producing a novel glycosaminoglycan derivative having the properties (a), (b) and (c) and having the specified structure defined in (d), comprising the following steps (i) and (ii) described below; and the third embodiment of the present invention relates to a pharmaceutical composition comprising the glycosaminoglycan derivative as an active ingredient:
(i) a step in which a sulfated glycosaminoglycan having a repeating unit structure of hexosamine and hexuronic acid as a backbone structure is subjected to a cleavage treatment to cleave between only the 2- and 3-position carbon atoms of at least a part of hexuronic acid having no sulfate group on the 2-position in the backbone structure, and
(ii) a step in which the product of the step (i) is subjected to a desulfation treatment by a desulfation method capable of specifically removing the 2-position sulfate group of hexuronic acid to desulfate 90% or more of sulfate groups of the total hexuronic acid having a sulfate group at the 2-position.
The present invention is described further in detail in the following.
As described above, the substance of the present invention is a novel glycosaminoglycan derivative which has the properties (a), (b) and (c) and also has the specified structure defined in (d).
The term xe2x80x9chexosaminexe2x80x9d as used herein means a monosaccharide in which the 2-position of hexose has an amino group, an acetylamino group or a sulfamino group and the 6-position hydroxyl group is optionally sulfated, the term xe2x80x9chexuronic acidxe2x80x9d means a monosaccharide in which the 6-position carbon atom of hexose forms a carboxyl group and the 2-position hydroxyl group is optionally sulfated, the term xe2x80x9cglycosaminoglycanxe2x80x9d means a polysaccharide which has a structure formed by a repeating unit of hexosamine and hexuronic acid as the backbone structure, and the term xe2x80x9csulfated glycosaminoglycanxe2x80x9d means a member of the glycosaminoglycan, which has hexosamine or hexuronic acid having a sulfate group as a constituting monosaccharide, and is a polysaccharide which has at least one hexuronic acid having no sulfate group at the 2-position as a constituting monosaccharide.
Also, the disaccharide composition (a) of the glycosaminoglycan derivative is calculated from values measured by a disaccharide analysis process which will be described later in Test Process 1 of Examples, and the weight average molecular weight (c) is a value measured by a molecular weight measuring process described in Test Process 2 of Examples. Also, the APTT of (b) is a value measured by an APTT measuring process described in Test Process 4 of Examples.
The disaccharide composition defined in (a) shows the ratio of each unsaturated disaccharide having a specified structure, which is calculated by defining the total amount of unsaturated disaccharides represented by the following general formula (7) as 100% (total mol % of 2-acetamido-2-deoxy-4-O-(4-deoxy-a-L-threo-hex-enopyranosyluronic acid)-D-glucose (hereinafter also referred to as xe2x80x9cxcex94DiHS-OSxe2x80x9d), 2-acetamido-2-deoxy-4-O-(4-deoxy-xcex1-L-threo-hex-4-enopyranosyluronic acid)-6-O-sulfo-D-glucose (hereinafter also referred to as xe2x80x9cxcex94DiHS-6Sxe2x80x9d), 2-deoxy-2-sulfamino-4-O-(4-deoxy-xcex1-L-threo-hex-4-enopyranosyluronic acid) -D-glucose (xcex94DiHS-NS), 2-acetamido-2-deoxy-4-O-(4-deoxy-2-O-sulfo-xcex1-L-threo-hex-4-enopyranosyluronic acid) -D-glucose (hereinafter also referred to as xe2x80x9cxcex94DiHS-USxe2x80x9d), 2-deoxy-2-sulfamino-4-O-(4-deoxy-xcex1-L-threo-hex-4-enopyranosyluronic acid)-6-O-sulfo-D-glucose (hereinafter also referred to as xe2x80x9cxcex94DiHS-di(6,N)Sxe2x80x9d), 2-deoxy-2-sulfamino-4-O-(4-deoxy-2-O-sulfo-xcex1-L-threo-hex-4-enopyranosyluronic acid)-D-glucose (hereinafter also referred to as xe2x80x9cxcex94DiHS-di(U,N)Sxe2x80x9d), 2-acetamido-2-deoxy-4-O-(4-deoxy-2-O-sulfo-xcex1-L-threo-hex-4-enopyranosyluronic acid)-6-O-sulfo-D-glucose (hereinafter also referred to as xe2x80x9cxcex94DiHS-di(U,6)Sxe2x80x9d) and 2-deoxy-2-sulfamino-4-O-(4-deoxy-2-O-sulfo-xcex1-L-threo-hex-4-enopyranosyluronic acid) -6-O-sulfo-D-glucose (xcex94DiHS-tri(U,6,N)S)) that can be identified by the disaccharide analysis described in Test Process 1 in which enzyme digestion and high performance liquid chromatography are used in combination, and the value reflects the position and number of sulfate groups of the glycosaminoglycan derivative before the enzyme digestion.
Also, the structures represented by the above abbreviations may also be shown as follows:
xcex94DiHS-OS: xcex94HexA1xe2x86x924GlcNAc, xcex94DiHS-6S: xcex94HexA1xe2x86x924GlcNAc(6S), xcex94DiHS-NS: xcex94HexA1xe2x86x924GlcNS, xcex94DiHS-US: xcex94HexA(2S) 1xe2x86x924GlcNAc, xcex94DiHS-di(6,N)S: xcex94HexA1xe2x86x924GlcNS(6S), xcex94DiHS-di(U,N)S: xcex94HexA(2S)1xe2x86x924GlcNS, xcex94DiHS-di(U,6)S; xcex94HexA(2S)1xe2x86x924GlcNAc(6S), and xcex94DiHS-tri (U,6,N)S: xcex94HexA(2S)1xe2x86x924GlcNS(6S).
In the above formulae, xcex94HexA means unsaturated hexuronic acid, GlcNAc means N-acetylglucosamine, GlcNS means N-sulfated glucosamine and the parenthesized part shows binding position of sulfate group.
The unsaturated disaccharide having the structure of general formula (7) formed in the disaccharide analysis process is formed from a backbone structure of (A)-(B) in general formula (2) in which the hexuronic acid of general formula (3) or (4) and the hexosamine of general formula (6), which constitute the backbone structure of glycosaminoglycan to be analyzed, are bonded to each other.
The glycosaminoglycan derivatives of the present invention are novel polysaccharides having specified physical properties derived from glycosaminoglycan, but are described herein as glycosaminoglycan derivatives for the sake of convenience.
The glycosaminoglycan derivatives of the present invention are sulfated polysaccharides in which, in the disaccharide composition calculated from the values measured by the disaccharide analysis process described in Test Process 1, mol % of xcex94DiHS-tri(U,6,N)S is from 0 to 10%, preferably from 0 to 5%, and more preferably from 2 to 4%, mol % of xcex94DiHS-di(6,N)S is from 95 to 70%, preferably from 90 to 80%, and more preferably from 82 to 87%, mol % of xcex94DiHS-NS is from 5 to 20%, preferably from 10 to 15%, and more preferably from 11 to 14%, and its weight average molecular weight as a value measured by the molecular weight measuring process described in Test Process 2 is from 9,000 to 13,000 Da, and more preferably from 10,000 to 12,000 Da.
Also, the glycosaminoglycan derivatives of the present invention are glycosaminoglycan derivatives which have a structure formed by the repeating unit of hexosamine and hexuronic acid as the backbone structure. Examples of the hexosamine include glucosamine, galactosamine and mannosamine, and glucosamine is preferred. It is preferred that one or both of the amino group and the 6-position hydroxyl group of hexosamine are sulfated, namely, it is N-sulfated and/or 6-O-sulfated, though there is no hindrance when the hexosamine has no sulfate group. Examples of the hexuronic acid include D-glucuronic acid, L-iduronic acid and the like. It is preferred that a part of hexuronic acid is cleaved between the 2- and 3-position carbon atoms, preferably, the cleaved region is reduced after oxidative cleavage reaction, and that a part or entire portion of the 2-position hydroxyl group of uncleaved hexuronic acid is not substituted with a sulfate group. In addition, one or more of the structural unit represented by general formula (1) in which the cleaved hexuronic acid is bonded to hexosamine in the repeating unit of the backbone structure is present in one molecule of the glycosaminoglycan derivative.
Also, the glycosaminoglycan derivatives of the present invention have a characteristic in that activated partial thromboplastin time (APTT) when measured by adding it to standard blood plasma at a final concentration of 3 xcexcg/ml is 50 seconds or less. The glycosaminoglycan derivatives of the present invention having such a characteristic can be represented by the following general formula (2):
HOxe2x80x94((A)-(B))nxe2x80x94Hxe2x80x83xe2x80x83(2)
In this formula, (A) represents a glucuronic acid residue represented by the following general formula (3), an iduronic acid residue represented by the following general formula (4), or a cleaved hexuronic acid residue represented by the following general formula (5):
and (B) represents a hexosamine derivative residue represented by the following general formula (6):
In general formulae (3) to (6), R1 and R3 each independently represents H or SO3H, and R2 independently represents COCH3or SO3H.
Also, a hexosamine residue represented by general formula (6) in which at least one of R1 and R2 is SO3H is present in-molecule of the glycosaminoglycan derivative of the present invention represented by general formula (2).
In addition, in general formula (2), n is an integer which satisfies 15xe2x89xa6nxe2x89xa640, preferably 20xe2x89xa6nxe2x89xa630, and at least one of (A) is a residue of general formula (5).
The glycosaminoglycan derivatives of the present invention (hereinafter referred also to as xe2x80x9cinventive substancesxe2x80x9d) are not particularly limited, so long as they are derivatives of a sugar chain using hexosamine and hexuronic acid as the backbone structure and have a sulfate group, and so long as they satisfy the characteristics of (a) to (d). However, derivatives of heparan sulfate or heparin, particularly derivatives of heparin, are preferred. The inventive substances have a structure in which a part of hexuronic acid is cleaved between the 2- and 3-position carbon atoms. Also, the sulfation ratio of the 2-position hydroxyl group of uncleaved hexuronic acid as a constituent of the inventive substances is less than 10%, preferably less than 5%. The glycosaminoglycan derivatives of the present invention can be represented by general formula (2), wherein n is 15xe2x89xa6nxe2x89xa640, preferably 20xe2x89xa6nxe2x89xa630, namely, they are polysaccharides having from 30 to 80 sugar residues, preferably from 40 to 60 sugar residues. In addition, since the anticoagulation activity of the substances is low, it is preferred that the activated partial thromboplastin time (APTT) when measured by adding them to a standard blood plasma sample collected from a healthy parson at a final concentration of 3 xcexcg/ml is 50 seconds or less.
In the neurite outgrowth promoting activity test described in Examples in which primary culture cells of Wistar rat cerebral cortex cells are used, it is preferred that the glycosaminoglycan derivatives as the inventive substances have 1.5 times or higher activity than the case of standard heparin when culturing is carried out by adding the substances at a final concentration of from 1 xcexcg/ml to 10 xcexcg/ml.
In addition, it is preferred that the inventive substances show markedly stronger sialidase inhibition activity, particularly influenza virus sialidase inhibition activity, than known sialidase inhibitors and standard heparin, when measured by the process described in Examples.
The production process of the present invention is a process for producing glycosaminoglycan derivatives having a repeating unit structure of hexosamine and hexuronic acid as the backbone structure, in which a part of hexuronic acid is cleaved between the 2- and 3-position carbon atoms, preferably, the cleaved region is reduced after cleavage by an oxidative cleavage reaction, and the greater part of the 2-position sulfate group of uncleaved hexuronic acid is desulfated, which comprises the following steps (i) and (ii):
(i) a step in which a glycosaminoglycan having a repeating unit structure of hexosamine and hexuronic acid as the backbone structure is subjected to a cleavage treatment to cleave between only the 2- and 3-position carbon atoms of at least a part of hexuronic acid having no sulfate group on the 2-position, and
(ii) a step in which the product of step (i) is subjected to a desulfation treatment by a desulfation method capable of specifically removing the 2-position sulfate group of hexuronic acid to desulfate 90% or more of sulfate groups of the hexuronic acid having a sulfate group at the 2-position.
1. Sulfated Glycosaminoglycan (Material)
The glycosaminoglycan used in the process of the present invention is a polysaccharide having a repeating unit structure of hexosamine and hexuronic acid as the backbone structure and containing at least one hexuronic acid having no sulfate group at the 2-position as a constituting monosaccharide. Preferred examples of the glycosaminoglycan include heparin, heparan sulfate, and the like, and heparin is particularly preferred, because the sulfation ratio of the 2-position hydroxyl group of hexuronic acid is high and the cleavage of hexuronic acid in the following step (i) can be appropriately controlled.
2. Step (i): Cleavage Treatment of Hexuronic Acid
The xe2x80x9ccleavage treatmentxe2x80x9d described in the step (i) of the process of the present invention is not particularly limited, so long as it is a treatment for specifically cleaving only between the 2- and 3-position carbon atoms of hexuronic acid having no sulfate group at the 2-position among constituting monosaccharides of sulfated glycosaminoglycan. Examples thereof include an oxidation-reduction treatment. This oxidation-reduction treatment is carried out by cleaving between the 2- and 3-position carbon atoms of the specified hexuronic acid through an oxidation reaction using an oxidizing agent to obtain an oxidatively cleaved reaction product and then reducing the aldehyde groups formed in the cleaved region of the hexuronic acid through a reduction reaction treatment. The oxidizing agent is not particularly limited, so long as it is a substance which can achieve the object of this reaction. Examples thereof include a periodate, hydrogen peroxide, and a periodate is particularly preferred. Examples of the periodate include periodic acid alkali metal salts, such as sodium periodate, potassium periodate and the like, and sodium periodate is preferred.
When an oxidation-reduction reaction treatment is carried out as the cleaving treatment, an oxidation reaction is carried out, for example, in a solution containing sodium periodate at a concentration of from 0.01 to 0.3 M preferably from 0.05 to 0.2 M, and the sulfated glycosaminoglycan at a concentration of from 0.5 to 10%, preferably from 1 to 7%, at a pH of from 3 to 7, preferably from 4 to 5, and at a treating temperature of from 0 to 37xc2x0 C., preferably from 0 to 10xc2x0 C., more preferably 4xc2x0 C., for at least 1 day, preferably 3 days. After the oxidation reaction, excess sodium periodate is decomposed through a reducing reaction by adding from 100 to 500 mM ethylene glycol or glycerol. Thereafter, an oxidative cleavage reaction product of hexuronic acid can be obtained by carrying out dialysis or further employing freeze-drying or ethanol precipitation process as occasion demands.
Thereafter, the oxidation-reduction reaction treatment of hexuronic acid is completed by further reducing the aldehyde groups formed in the cleaved region of hexuronic acid by periodic acid oxidation. The reduction of aldehyde groups can be carried out using a reducing agent such as an alkali metal borohydride or lithium aluminum hydride, and the reducing agent is preferably an alkali metal borohydride, most preferably sodium borohydride. When sodium borohydride is used as the reducing agent, it is preferred to carry out the reaction, for example, in a solution of pH 8.5 to 9.5 containing from 0.1 to 0.5 M, preferably 0.2 M, of sodium borohydride and from 1 to 20%, preferably from 5 to 10% of the oxidative cleavage reaction product (w/v), at 4xc2x0 C. for 3 hours. It is preferred to obtain a sodium salt of the periodic acid oxidation-reduction reaction product by further decomposing excess sodium borohydride by adjusting the reaction solution to pH 4 to 5 and then terminating the reduction reaction by dialyzing it against distilled water.
Particularly, when heparin is used as the material, it is preferred to carry out the cleavage treatment by an oxidation-reduction reaction treatment using a periodate and an alkali metal borohydride, and a periodic acid oxidation-reduction heparin is obtained by this treatment as a periodic acid oxidation reduction product of heparin.
The hexuronic acid cleavage product of sulfated glycosaminoglycan obtained by the treatment to specifically cleave hexuronic acid among the constituting monosaccharides of sulfated glycosaminoglycan is subjected to the subsequent step (ii) in which the 2-position sulfate group of at least a part of hexuronic acid is desulfated.
3. Step (ii): Desulfation Treatment
The xe2x80x9cdesulfation treatmentxe2x80x9d described in the step (ii) of the process of the present invention can be carried out without particular limitation, so long as it is a treatment (selective desulfation treatment) to selectively desulfate the 2-position sulfate group of the hexuronic acid having a sulfate group at the 2-position, which constitutes the xe2x80x9chexuronic acid cleavage product of sulfated glycosaminoglycanxe2x80x9d formed in the step (i). When complete desulfation is desired, it is preferred to employ a process which is carried out under alkaline conditions, namely a process by hydrolysis reaction, particularly a process which includes a step in which the hexuronic acid cleavage product of sulfated glycosaminoglycan obtained in the step (i) is dissolved in an aqueous solution of an alkali metal hydroxide, such as sodium hydroxide, potassium hydroxide, or the like, or an aqueous solution of an alkaline earth metal hydroxide, such as magnesium hydroxide, calcium hydroxide, or the like, preferably an aqueous alkali metal hydroxide solution, most preferably an aqueous sodium hydroxide solution, and the resulting solution is immediately frozen to carry out freeze-drying.
Specifically, a solution of the hexuronic acid cleavage product of glycosaminoglycan is prepared by dissolving the hexuronic acid cleavage product of glycosaminoglycan in an aqueous alkali metal hydroxide solution or aqueous alkaline earth metal solution having a concentration of from 0.0125 to 0.2 N, preferably at ice-cooling (0xc2x0 C.) to room temperature (24xc2x0 C.), and then the resulting solution is freeze-dried. Thereafter, it is preferred that the freeze-dried product is again dissolved in an aqueous alkali metal hydroxide solution or aqueous alkaline earth metal solution (0.0125 to 0.2 N) to a concentration of from 1 to 2.5 M, preferably 2 M, and the resulting solution is adjusted to pH 8 to 10 with an acid, preferably a weak acid, more preferably a carboxylic acid, such as acetic acid or the like, and immediately subjected to dialysis against distilled water for at least 1 day, preferably 2 days, followed by freeze-drying or ethanol precipitation.
Desulfation of the hexuronic acid cleavage product of sulfated glycosaminoglycan is carried out in such a manner that generally 70% or more, preferably 90% or more, more preferably 95% or more, of the 2-position sulfate groups of uncleaved hexuronic acid are removed.
According to the process of the present invention, when the partial desulfation treatment is carried out using the periodic acid oxidation-reduction heparin obtained in the step (i) from heparin as the material sulfated glycosaminoglycan, the partially 2-O-desulfated periodic acid oxidation-reduction heparin of the present invention is obtained.
A schematic illustration of the reaction steps for the production of the glycosaminoglycan derivative of the present invention from heparin as the starting material by the cleavage treatment of step (i) and the desulfation treatment of step (ii) is shown in FIG. 1. In the drawing, (a) is a schematic representation of heparin, (b) is a reaction product in which aldehyde groups are formed by the oxidative cleavage reaction of hexuronic acid, (c) is a reduction reaction treated product obtained by the reduction reaction treatment of the aldehyde groups of (b), and (d) is a glycosaminoglycan derivative of the present invention in which the 2-O-sulfate group is selectively desulfated.
Composition 1 of the present invention is a therapeutic agent for neurological disorders, comprising, as an active ingredient, the inventive substance, a glycosaminoglycan derivative or a pharmaceutically acceptable salt thereof.
The glycosaminoglycan derivatives having neurite outgrowth promoting activity are useful as a pharmaceutical composition using the activity, such as a neuronal disease treating agent for, for example, central nerve diseases (e.g., Alzheimer disease, ischemic dementia, etc.) or peripheral nerve diseases (e.g., diabetic neuropathy, alcoholic neuropathy, amyotrophic lateral sclerosis (ALS), peripheral nerve damage caused by injury or side effect of medicament, Guillain-Barre syndrome, etc.).
Also, the glycosaminoglycan derivatives of the present invention which are the active ingredient of Composition 1 of the present invention can also be applied to therapeutic and preventing agents as a nervous function reduction inhibitor, because they can prevent reduction of nervous functions accompanied by nerve degeneration, by inhibiting the activity of sialidase to degrade cell membrane ganglioside which is concerned in the maintenance of neural cell survival, synaptic function and axon function.
Composition 2 of the present invention is a sialidase inhibitor, comprising, as an active ingredient, the inventive substance, a glycosaminoglycan derivative or a pharmaceutically acceptable salt thereof.
The glycosaminoglycan derivatives having sialidase inhibition activity as the inventive substances can be used as a sialidase inhibitor using its activity. Particularly, since they can inhibit growth of viruses by inhibiting viral sialidase, they can be used as an anti-viral agent, particularly as an anti-influenza remedy. Particularly, the inventive substances show markedly more excellent sialidase inhibition activity than known sialic acid derivatives used as influenza remedies.
The term xe2x80x9cremedyxe2x80x9d as used herein includes not only drugs for improving conditions of patients into normal states and drugs for alleviating diseases but also a concept of xe2x80x9cdrugs for preventionxe2x80x9d for preventing infection with and contraction of diseases.
Examples of the pharmaceutically acceptable salts of the glycosaminoglycan derivatives, which are used as the active ingredient of Compositions 1 and 2 of the present invention include pharmaceutically acceptable salts among amine salts, quaternary ammonium salts, alkali metal salts and alkaline earth metal salts. Specific examples include sodium salts, potassium salts, calcium salts, magnesium salts, and the like, and sodium salts and potassium salts as alkali metal salts are preferred, and sodium salts are more preferred, for example, in view of the affinity for the living body.
The glycosaminoglycan derivatives of the present invention show a characteristic of being lower in anticoagulation activity than standard heparin. In especially desirable glycosaminoglycan derivatives, it is most preferred that the APTT value becomes 50 seconds or less when measured in accordance with the process shown in Test Example 4 which will be described later, by setting the concentration in the measuring solution (final concentration) to 3 xcexcg/ml. Also, regarding the glycosaminoglycan derivative (the inventive substance) used in the composition of the present invention as a pharmaceutical composition, it is preferred that at least one of thrombin time (hereinafter referred to as xe2x80x9cTTxe2x80x9d) calculated by a TT measuring process which will be described later and APTT activity calculated by the APTT measuring process becomes 5% or less in comparison with standard heparin. Still more preferably useful is a substance having a relatively low TT activity, in which the TT activity and the APTT activity are both 3% or less in comparison with standard heparin and both of these activities have a relationship of 0xe2x89xa6TT activity/APTT activityxe2x89xa60.5, because low bleeding activity can be expected when used in a pharmaceutical composition.
The term xe2x80x9cstandard heparinxe2x80x9d as used herein means a substance identical to the standard heparin described in Examples.
When a pharmaceutical composition containing the inventive substance as the active ingredient is administered to the living body, the dosage form and route of administration can be optionally selected in response to the properties and seriousness of the disease to be treated. For example, it can be safely administered parenterally or orally to a warm-blooded animal (e.g., human, mouse, rat, hamster, rabbit, dog, cat, horse, etc.) as it is or as pharmaceutical composition preparations together with other pharmaceutically acceptable additives, such as carriers, fillers, diluents and the like (e.g., injections, suppositories, tablets, capsules, solutions, ointments, gels, etc.).
Regarding the administration form of the therapeutic agent for neuronal diseases, parenteral administration is preferred, injections can be cited as the dosage form suitable for the administration form, and intravenous injection or drip infusion can be exemplified as preferred mode of the administration process, though not limited thereto.
Regarding the administration form of the influenza remedy, any of its oral and parenteral administration forms can be optionally selected. Examples of the dosage form suitable for oral administration include powders, granules, tablets, capsules, aerosols and sprays, and solutions can be exemplified as the dosage form suitable for parenteral administration. In addition, as the dosage form of the influenza remedy particularly for prevention, solutions used by oral administration are also preferred, and administration of the solutions using a spray or the like can be cited as a preferred process, though not limited thereto.
A formulating amount and a dose of the glycosaminoglycan derivative as the active ingredient of the preparation are not particularly limited, because they should be decided individually depending on, for example, the administration process, administration form and using purpose of the preparation and illustrative symptoms and body weight of each patient, but in the case of intravenous injection, approximately from 100 xcexcg/kg to 100 mg/kg per day can be exemplified as the amount of the glycosaminoglycan derivatives to be administered to a patient. Also, regarding the administration frequency of the preparation, once a day is possible, and it can also be administered by dividing the daily dose into 2 to 4 or more doses per day. It is also possible to administer it continuously by, for example, drip infusion.
In this connection, the glycosaminoglycan derivative as the active ingredient of the pharmaceutical composition showed no toxicity upon cells in the following Examples. It is known that the LD50 value of heparin by an acute toxicity test in mice (males and females) is 5,000 mg/kg or more by oral administration, 2,500 mg/kg or more by subcutaneous or intraperitoneal administration and about 1,000 mg/kg by intravenous injection. Since the glycosaminoglycan derivatives as the active ingredient of the pharmaceutical composition of the present invention show markedly low APTT activity and TT activity of both less than 3% in comparison with the standard heparin, this fact also supports high safety of the glycosaminoglycan derivatives (the inventive substances) which are the active ingredient of the pharmaceutical composition.

Glycosaminoglycan derivatives and processes for preparing same


An apparatus used to arrange and display decorative items or candy. A narrow stem comprises a plurality of holes running throughout the stem. A plurality of metal rods are inserted into respective holes in the stem. Each metal rod has is attached to a plastic petal, which also comprises a clip. A piece of candy can be attached to each clip and can be supported by each respective petal. The plurality of metal rods arranged in this manner create a visually appealing arrangement of decorative items or dispenser of candy.

1. Field of the Invention
The present general inventive concept is directed to an apparatus for arranging candy or small decorative items in an aesthetically pleasing arrangement.
2. Description of the Related Art
Candy arrangements are well known in the art and are sent as gifts.
However, what is needed is an apparatus that can arrange candy in an aesthetically pleasing manner which can also allow for easy removal of individual candy pieces by the owner.

This patent is subject to a terminal disclaimer.


A composition is provided for faster bone repair and early orthopedic implant fixation. The composition comprises an osteoinductive or osteopromotive biological factor embedded in a carrier slurry. The slurry is prepared by wetting a biodegradable polymer and calcium phosphate particles with a biocompatible fluid. The composition may be applied to the site of the bone fracture, to an orthopedic implant or to both during the surgical procedure. The composition utilizes low dosages of the biological factor and, therefore, is cost effective to be used routinely.

The human skeleton is made up of 206 bones. The bones, also called osseous tissue, are a type of hard endoskeletal connective tissue that supports body structures, protects internal organs, and (in conjunction with muscles) facilitates movement. Unfortunately, bones are subject to fracturing as a result of physical trauma or certain medical conditions that weaken the bones, such as osteoporosis or certain types of cancer. Although fractured bones can heal by natural processes, it may sometimes be necessary to reinforce or stabilize the bones with metal implants during the healing process.
More importantly, replacing a joint affected by osteoarthritis ("OA") with a prosthetic device is a common procedure. OA is a degenerative joint disease characterized by progressive break down of the cartilage matrix. Cartilage is the part of the joint that cushions the ends of the bones and allows easy movement of joints. It also absorbs energy from the shock of physical movement. The breakdown of cartilage causes the bones to rub against each other, causing stiffness, pain and loss of movement in the joint. OA affects approximately 21 million Americans a year, accounting for 25% of visits to primary care physicians. It is estimated that 80% of the population will have radiographic evidence of OA by age 65 with more than 60% of those exhibiting symptoms.
If the joint does not respond to conservative treatment such as medication, weight loss, activity restriction, and use of walking aids such as a cane, joint replacement with a prosthetic device is considered appropriate. The most common joints to be replaced are knees and hips. About 435,000 Americans have a hip or knee replaced each year. Research has shown that joint replacement can help even older patients to move around and feel better. For a joint replacement to succeed, the prosthetic replacements require rapid bone ingrowth in them to stabilize the implant and allow the patient to resume the normal activities of daily living.
The mechanical disturbance of the bone after fracture or during surgery may, however, delay its repair and regeneration resulting in transient instability of the implant. In addition, it may lead to a fibrous tissue interposition between the bone and the implant which may lead to loosening of the implant. Loosening of the joint is the most common cause of failure in hip joints that are not infected. This may require another joint replacement surgery in about 12% of patients within a 15-year period following the first procedure. Thus, younger patients may need to have the same damaged joint replaced more than once.
Prior attempts have been made to modify the surface of orthopedic implants with biological substances to promote faster bone repair and to facilitate early implant fixation. Because in these prior art attempts the implant is coated during the manufacturing process, pre-application of a biologically active substance at the time of manufacture increases the cost of the surgical procedure because excessive amounts of the expensive biological factor are needed during the manufacturing process and to ensure it's long term sterility and stability. In addition, pre-applying the biological substance at the time of manufacture also does not allow a surgeon to customize the amount of a biologically active substance applied to the implant for a particular procedure.
Accordingly, there is still a need in the art for a intraopertive, user-friendly, flexible, and relatively inexpensive method to facilitate early implant fixation.

Flowable carrier compositions and methods of use


The present invention relates to a process for desalting aqueous suspensions containing an organic diazonium compound and electrolytes containing Na ions, in which the aqueous suspension is passed through a semipermeable membrane.

The present invention relates to a process for the production of diazonium compounds with a low content of sodium ions and the use of the resulting compounds for the preparation of azo compounds, and in particular azo dyes.
Most dye applications require dyes which are highly soluble in water. Some salt forms of dyes containing sulfo or carboxy groups are for example less water-soluble than others. The corresponding sodium salts or sodium mixed salts, such as for example Na/K salts, frequently have particularly low solubility. Where possible it is therefore desirable to prepare dyes from other salt forms, such as for example lithium, potassium or ammonium salts. Particularly in the case of dye salts of relatively low solubility conversion into the corresponding more highly water-soluble salt forms is very complicated since high dilution rates are required and considerable quantities of effluent result.
Attempts are therefore made to use starting materials which are already in free from or have only a low content of sodium ions in the coupling reaction for the preparation of corresponding azo compounds, and in particular azo dyes.
Diazonium compounds, which are generally obtained by the diazotization of the corresponding amines with sodium nitrite in the presence of inorganic acids, are frequently obtained in the form of water-insoluble compounds which can be filtered off and then washed with water until free of sodium ions. This process is problematical from the point of view of safety, since the filter cake can dry onto the membrane and, on exposure to impact or heat, the explosive decomposition of the diazonium compounds, which are known to be unstable in the dry state, is then likely to occur.
A process has now been found which avoids the above-mentioned disadvantages.

Process for the production of diazonium compounds with a low content of sodium ions


A shift control system of a hybrid transmission for a vehicle is arranged to correct ideal motor/generator torques so as to achieve a target engine speed prior to a target driving torque when an actual engine speed becomes greater than an allowable upper-limit engine speed and to correct the ideal motor/generator torque so as to achieve the target driving torque prior to the target engine speed when the actual engine speed does not become greater than the allowable upper-limit engine speed.

The present invention relates a hybrid drive system constructed by an internal combustion engine and a hybrid transmission including a differential mechanism and two motor/generators, and more particularly to a shift control system which appropriately executes a shift control of the hybrid transmission so as not to generate a strange acceleration/deceleration or an exceeding engine revolution due to an unnatural change of a driving torque or transmission ratio.
It is known that a hybrid transmission is generally constructed by relationally connecting an internal combustion engine, an output shaft, two motor/generators and a differential mechanism to execute a shifting through the control of the two motor/generators. Such a hybrid transmission is arranged to drive the motor/generators using electric power of a battery. Accordingly, it is necessary to limit the electric power used for the motor/generators at a value smaller than a rated electric power of the battery as is similar to the limitation of an electric device installed in a vehicle.
Japanese Published Patent Application No. 2002-058113 discloses a power control method of the motor/generators for a hybrid vehicle. More specifically, the power control method is basically applied to a power output system which comprises at least an electric device operated according to charging/discharging of a battery, and corrects a target output of the electric device at a value which requires a power smaller than a rated momentary electric power of the battery when the electric device outputs the target output requiring a power greater than the rated momentary electric power.

Shift control system of a hybrid transmission with a motor torque correction