A surface emitting semiconductor laser includes a substrate, a first semiconductor multilayer reflector formed on the substrate, an active region formed on the first semiconductor multilayer reflector, a second semiconductor multilayer reflector formed on the active region, a current confinement layer interposed between the first and second semiconductor multilayer reflectors and partially including an oxide region, and an insulating layer formed on a coated surface provided by a semiconductor layer which is part of the first semiconductor multilayer reflector and is revealed after removal of a surface oxidation layer.

The present invention relates to a surface emitting semiconductor laser typically used for optical interconnections, optical switch and optical information processing, and a process for producing such a laser.
Recently, there has been considerable activity in the development of optical interconnections directed toward dramatically improved transmission rates as means for transmitting information between logic circuit elements. Attention is attracted to a surface emitting semiconductor laser that enables light-emitting elements to be densely arranged in two dimensions as a parallel source. Such a laser is frequently called vertical cavity surface emitting laser diode (which will be hereinafter referred to as VCSEL simply). Pioneer researches in the VCSEL have been conducted by Ueki et al., "Single-Transverse-Mode 3.4-mW Emission of Oxide-Confined 780-nm VCSEL's", IEEE PHOTONICS TECHNOLOGY LETTERS. VOL. 11, NO. 12, DECEMBER 1999, pp.1539–1541.
Referring to FIGS. 5A and 5B, a recent structure of the VCSEL has a resonator 702 that vertically extends from the horizontal surface of a semiconductor substrate 701. The resonator 702 has a mesa structure, and includes an active layer 703, a lower reflection mirror 704, an upper reflection mirror 705, and a spacer layer 706. The active layer 703 confines a carrier and results in light. Each of the mirrors 704 and 705 is made up of a plurality of semiconductor layers. The spacer layer 706 makes phase matching of the light emitted by the active layer 703 at the ends of the reflection mirrors 704 and 705. On the upper reflection mirror 705, provided are an upper contact layer 707, an upper electrode 708, an interlayer insulating film 710 and a lower electrode 709 in this order. The upper electrode 708 defines an aperture via which the laser beam is emitted. The interlayer insulating film 710 covers the sidewall and upper edge portions of the mesa structure.
Laser oscillation is conducted by confining the carrier and light in the horizontal direction in addition to the vertical direction. A confinement structure in the horizontal direction with respect to the substrate may be constructed by any of the following methods. The first method employs dry etching by which a boss (post or mesa) structure as thin as about ten and a few microns is formed. The second method is of oxidization type. A post structure having a diameter as large as tens of microns by dry etching and the property of an AlAs layer called control layer is partially changed into insulation by moisture vapor oxidation so that a restricted current path can be defined. The third method is of implantation type. The third method forms an insulating region by proton implantation and results in the restricted current path. At present, it is acknowledged that the oxide-confined VCSEL has a comparatively low threshold current and exhibits an excellent optical characteristic as a function of current. This is described in, for example, Journal of Solid State Physics and Applications Division, Vol. 5, No. 1, 1999, pp. 11. In FIGS. 5A and 5B, an oxide region in the AlAs layer 712 is indicated by a reference numeral 712A, and a non-oxide region therein is indicated by a reference numeral 712B. An aperture 713 is formed in the upper electrode 708 and the laser beam is emitted via the aperture 713. FIG. 5A and 5B differ from each other in that the semiconductor layer on which the interlayer film located on the bottom of the mesa structure is formed is a surface-oxidized layer 714 of a GaAs layer of the semiconductor substrate 701 or a surface-oxidized layer 715 of an AlGaAs layer that is part of the lower reflection mirror 704. The above difference results in a difference in the post height.
A description will now be given, with reference to FIGS. 6A through 6F, of steps of the process for producing the oxide type VCSEL until the interlayer insulating film is provided.
Referring to FIG. 6A, on an n-type GaAs semiconductor substrate 801, provided are an n-type GaAs buffer layer 802, a distributed Bragg reflector layer (DBR layer) 803, a λ (one wavelength) Al0.6Ga0.4As spacer layer 804, an AlAs layer 807, a DBR layer 808 and a p-type GaAs cap layer 809 in this order by MOCVD (Metalorganic Chemical Vapor Deposition). The DBR layer 803 is composed of 35 n-type Al0.3Ga0.7As/Al0.9Ga0.1As layers. The spacer layer 804 has two Al0.10Ga0.90As quantum well active layers 805, and three Al0.30Ga0.70As barrier layers 806. One of the two layers 805 is sandwiched between two of the barrier layers 806, and the other layer 805 is sandwiched between two of the layers 806. It is to be noted that FIG. 6A shows only one barrier layer 806, and the two remaining barrier layers 806 provided on the upper surface of the upper active layer 805 and the lower surface of the lower active layer 805 are omitted for the sake of simplicity. It may be said that the barrier layers 806 that are omitted from illustration are interposed between the active layers and the spacer layers. The DBR layer 808 is composed of 28 p-type Al0.3Ga0.7As/Al0.9Ga0.1As pairs. The cap layer 809 functions as a contact layer. The layers thus laminated form a VCSEL substrate.
Next, as shown in FIG. 6B, a resist pattern for forming a contact electrode on the p-type GaAs cap layer of the VCSEL substrate is formed by the conventional photolithograph process (PLP). Then, an electrode metal such as Cr/Au or Ti/Au is deposited. Subsequent liftoff of the resist results in contract electrodes 810.
Then, as shown in FIG. 6C, an insulating film such as a SiON or SiO2 film acting as a mask in dry etching is deposited in order to define the post or mesa structure. Then, the insulating film is etched by buffered hydrofluoric acid (BHF) wherein resist formed by the conventional PLP is used as the mask. Thereby, an insulating mask 811 is defined.
As shown in FIG. 6D, the wafer is dry-etched in a mixture gas of BCl3 and Cl2 with the mask pattern 811 of the insulating film. This results in a post structure 812 on the VCSEL substrate. The height of the post structure may be defined by the any of two ways of etching described below. The first way of etching progresses beyond the DBR layer 803 composed of 35 n-type Al0.3Ga0.7As/Al0.9Ga0.1As layers and reaches the GaAs substrate 701, as shown in FIG. 5A. The second way stops etching in the course of etching the DBR layer 803. As shown in FIG. 5A, when the GaAs substrate 801 as well as the DBR layer 803 are etched, the resultant post structure is too high to maintain the satisfactory accuracy in the post process. Particularly, there may be difficulty in production of a dense element array. With the above in mind, it is preferable that the height of the post structure is restricted so that etching is stopped in the course of etching the DBR layer 803.
Then, as shown in FIG. 6E, the VCSEL substrate on which the post structure 812 has been formed is oxidized in moisture vapor ambience at an anneal temperature of 350° C.–450° C. The AlAs layer 807 exposed to the sidewall of the post structure 812 is oxidized toward the center of the post structure 812 from the end thereof, so that an oxide region 813 dependent on the oxidizing time can be formed. The oxide region 813 is a porous insulating film, which serves as a current blocking layer for current confinement. A remaining AlAs region 814 that has not been oxidized (non-oxide region) defines a current path. The non-oxide region 814 has a refractive index different from that of the oxide region 813, and therefore acts as an aperture for controlling the horizontal mode of laser light.
Thereafter, as sown in FIG. 6F, the entire post structure is coated with a SiNex, SiO2 or SiOxNy film by CVD, so that an interlayer insulating film 815 can be formed. This is intended to reinforce the post structure because the oxidized region of the AlAs layer 807 is a porous thin film and is structurally weakened. Japanese Unexamined Patent Publication No. 11-340565, the applicant of which is the same as the assignee of the present application, discloses the use of an AlAs control layer (current confinement layer) that has an Al composition of 100%. The above publication proposes to reinforce the mesa structure by coating it with an interlayer insulating film in order to solve a problem such that the mesa structure after the oxidization process may be removed due to a post process of rapid annealing. Next, an electrode material is deposited, and is then annealed at about 400° C. in order to make the electrode ohmic.
However, the interlayer insulating film 815 may be released from the coated surface on the bottom of the mesa structure in annealing at about 400° C. for making the electrode ohmic. In some VCSEL substrates, the interlayer insulating film 815 may float above the coated surface or may be totally separated from the mesa structure. If the degree of separation is too bad, the interlayer insulating film 815 may go into pieces and may be scattered. The above reduces the number of normal VCSEL elements and degrades the reliability thereof. As a result, the yield of VCSEL elements may be degraded to tens to 50%.

Surface emitting semiconductor laser and process for producing the same including forming an insulating layer on the lower reflector


A substrate processing apparatus includes a plurality of vacuum transfer modules including transfer mechanisms for transferring a substrate between a plurality of process modules arranged near the vacuum transfer modules that are configured to process the substrate under a reduced-pressure atmosphere; one or more load lock modules provided at each of the vacuum transfer modules; a first atmosphere transfer mechanism that transfers the substrate that is fed from outside to one load lock module; and a second atmosphere transfer mechanism that receives the substrate from the first atmosphere transfer mechanism and transfers the received substrate to another load lock module. The second atmosphere transfer mechanism is arranged above or below the vacuum transfer module that is provided with the one load lock module, and the vacuum transfer modules are arranged in series along a substrate transfer direction of the second atmosphere transfer mechanism.

Multi-chamber substrate processing apparatuses are known that have multiple vacuum processing devices arranged near a vacuum transfer module, the vacuum processing devices being configured to perform various substrate processes on a semiconductor wafer, such as film formation, etching, oxide diffusion, annealing, or modification. The multi-chamber processing apparatus is configured to successively perform requisite substrate processes on a wafer by transferring the wafer between the vacuum process modules via the vacuum transfer chamber. By clustering plural vacuum processing devices in this manner, the substrate processing throughput may be improved.
Patent Document 1 discloses a tandem-type substrate processing apparatus in which two clustered multi-chamber devices are connected in series via a gate valve, and a relay chamber is provided for transferring a wafer between vacuum transfer modules of first and second clusters. The first cluster includes a load lock module, and a wafer is transferred to the vacuum transfer module of the first cluster via the load lock module. The wafer transferred to the vacuum transfer module of the first cluster successively undergoes a number of substrate processes at vacuum process modules of the first cluster. When the substrate processes at the first cluster are completed, the wafer is transferred to the second cluster via the relay chamber. At the second cluster, a number of substrate processes are successively conducted on the wafer in a manner similar to the first cluster. When the substrate processes are completed, the processed wafer follows the same path in reverse order to be discharged.
Patent Document 2 discloses a substrate processing apparatus in which only vacuum process modules that require a substrate to be passed under a reduced-pressure atmosphere are connected to a vacuum transfer module to form one cluster, and vacuum process modules that are allowed to pass a substrate to/from each other under air atmosphere are each connected to an atmosphere transfer module via load lock modules. Patent Document 2 also discloses a substrate processing apparatus in which two clusters are arranged in parallel along a wafer transfer direction of an atmosphere transfer mechanism and a wafer supplied from outside is transferred to the load lock modules of the clusters.


A method and apparatus for determining the location of an object with a sensor positions an instrument at a first location, controls the instrument to transmit a first omnidirectional signal during a first time, and determines a first distance from the instrument to the static object using the first omnidirectional signal. The method and apparatus repeats this process in a serial manner at two other locations, and uses the respective distances from each location to determine the location of the object. Other embodiments are disclosed.

Large area spaces often are used to store equipment and other objects. For example, a storage area for a large construction site (e.g., a municipal project, such as a power plant) can have many thousands of objects that are required to build the power plant. Among other things, those objects can be sophisticated electronics, wood, bags of concrete, wiring, piping, tools, equipment, trucks, etc.
Keeping track of the inventory at many large sites, however, often presents a significant challenge. For example, finding a prescribed object in a storage area spanning several acres can be daunting and take a lot of time. One common method for finding a prescribed object may involve simply using a picture of the large site. Undesirably, the picture may not have the requisite resolution, making it hard to read. This undesirably wastes time and possibly causes the person looking for the object not to find that object. In the latter case, more costs may be incurred to re-acquire the "missing" object.

Method and apparatus for determining the location of a static object


Co-fabricating non-planar (i.e., three-dimensional) semiconductor devices with different threshold voltages includes providing a starting semiconductor structure, the structure including a semiconductor substrate, multiple raised semiconductor structures coupled to the substrate, at least two gate structures encompassing a portion of the raised structures, each gate structure including a gate opening lined with dielectric material and partially filled with work function material, a portion of the work function material being recessed. The co-fabrication further includes creating at least one conformal barrier layer in one or more and less than all of the gate openings, filling the gate openings with conductive material, and modifying the work function of at least one and less than all of the filled gate structures.

Technical Field
The present invention generally relates to semiconductor device threshold (or "turn-on") voltage. More particularly, the present invention relates to the co-fabrication of non-planar semiconductor devices with different threshold voltages.
Background Information
Presently, the main approach to co-fabricating non-planar semiconductor devices (i.e., plasma doping) suffers drawbacks. For example, plasma doping can suffer short channel effects, due to the difference in the life time of plasma for short and long channels. Whatever fabrication method is used, it should be simple, repeatable and offer the option of fine-tuning the threshold voltages.
Thus, a need exists for improvement in co-fabricating non-planar semiconductor devices with different threshold voltages.

Co-fabrication of non-planar semiconductor devices having different threshold voltages


Certain aspects of the present disclosure provide techniques for improved control of workflow execution. Embodiments include receiving, by an execution engine, a request from a user to execute a workflow that is stored in a repository. The workflow may be an operation that is associated with an operation privilege level, and a user privilege level of the user may be a lower privilege level than the operation privilege level. Embodiments include determining a repository privilege level associated with the repository by accessing repository privilege data in a file stored on the repository. Embodiments include escalating the user privilege level to the repository privilege level. Embodiments include executing the workflow, based on the request from the user, at the repository privilege level. Embodiments include restoring the user privilege level to the lower privilege level.

Using a computing system may involve the use of workflows, wherein a workflow is a sequence of steps and/or operations to be performed by the computing system. Applications may involve the execution of workflows by users with different privilege levels. For example, an application may have normal users and administrative users with access to different workflows. That is, certain workflows or operations within workflows may be limited to entities with certain privilege levels, such as administrative users.
In some applications, there may be operations or workflows that are generally restricted to users of a certain privilege level, but which are applicable to users of a different privilege level under certain circumstances. For example, access to a particular computer system may generally be limited to administrative users, but an administrative user may wish to allow non-administrative users to access the system for certain purposes, such as to run virus scans on the particular computer system. As such, there is a need in the art for improved methods of controlling workflow execution.

Repository-based privilege escalation for workflows


A combination thermal and vibration sensor for use in sleep monitoring equipment comprises a thin film of a plastic exhibiting both pyroelectric and piezoelectric properties. By providing a layer of foam material totally covering one major surface of the plastic film layer, it is found that the thermal mass of the sensor is changed to the point where the pyroelectric signal can more readily be isolated from the piezoelectric signal using conventional signal processing techniques.

1. Field of the Invention
This invention relates generally to electronic sensors for monitoring both temperature changes and sound using a single transducer, and more particularly to the construction of such sensors that more readily allows the temperature signal to be separated from the sound signal using conventional signal processing techniques (filtering).
2. Discussion of the Prior Art
In the Stasz U.S. Pat. No. 5,311,875, which is hereby incorporated by reference, there is described a system for electronically monitoring breathing patterns. The system described therein utilizes a plastic film exhibiting both pyroelectric and piezoelectric properties such as a polyvinylidene fluoride (PVDF) film. The film transducer has a conductive electrode on opposed major surfaces thereof and electrical wires connect the electrodes to an electronics module that is designed to separate the transducer output into two separate channels, one being for temperature and the other being for sound or vibration.
Our testing has shown that the signal proportional to temperature variation greatly exceeds that due to noise or vibration by a factor of about 150:1. The temperature-related signal also exhibits a substantially faster response time than the sound signal and is rich in frequency components in the 20 Hz to 50 Hz range. These facts result in a difficulty in preventing the thermal component of the transducer from crossing over into the sound channel, often leading to the occurrence of false positives when both sound signals and temperature signals are being simultaneously monitored.
The problem thus presents itself as to how one may effectively separate the signals when the frequency components of each signal overlap. Resorting to a signal processing approach has proven difficult.
We have found that by modifying the mechanical construction of the pyro/piezo transducer to increase its thermal mass, the effective rise time of the thermal signal is greatly reduced, while not seriously attenuating the sound/vibration-related signal amplitude. Decreasing the rise time of the thermal signal results in a shift of the frequency components thereof so as not to overlap with the frequency components in the sound channel. As such, conventional filtering steps can be performed to produce separate, isolated channels.
In accordance with the present invention, control over the thermal mass of the transducer described in the aforereferenced Stasz patent is achieved by affixing a layer of plastic foam material onto the transducer film on at least one major surface thereof. Thus, in accordance with a preferred embodiment of the present invention, the combination thermal and vibration sensor may comprise a PVDF film of a predetermined shape configuration with first and second major surfaces. A thin layer of a conductive material is deposited upon the first and second major surfaces of the film and electrical leads are attached at one end to the electrodes. An outer moisture impervious layer is adhered to the electrode on one side of the film and a foam layer of a predetermined thickness and coextensive with the area of the PVDF film is bonded to the opposite major surface. The thickness of the foam layer is directly related to the rise time of the thermal signal. Lowering the rise time of the thermal signal effectively shifts the frequency components comprising the thermal signal so as to no longer overlap with the predominant frequency components of the piezo or sound signal. Now, conventional filtering techniques can be used to separate the two channels.


In various embodiments, an optical unit for a radiation source matrix is provided. The optical unit may include a plurality of coupling surfaces, which are arranged in at least one line, and at least one decoupling surface. At least one coupling surface, which is arranged at a line end of the line formed by the coupling surfaces arranged in at least one line, is widened when viewed in the direction of the at least one line.

So-called matrix headlights for vehicles are known. They have a matrix made of light-emitting diodes (LEDs). In this case, each individual LED can be separately activated and in this way turned on and off and also dimmed. The LEDs can be arranged in a single line or multiple lines and each form a light pixel.

Primary optical unit, secondary optical unit, module, arrangement, vehicle headlight, and headlight system


A system for selectively delivering different beverages having different foam levels by injection of a fluid under pressure into a capsule that contains a beverage-forming substance. The capsules include a chamber containing the substance and a beverage dispensing structure adapted to retain a certain extraction pressure in the chamber before allowing the beverage to flow out of the capsule. The system is characterized in that first and second capsules are provided for selective use in the system, with the first capsule having a first beverage dispensing structure configured and positioned therein to retain a first extraction pressure in the capsule, prior to the complete delivery of the beverage, and the second capsule having a second beverage dispensing structure configured and positioned therein to retain a second extraction pressure in the capsule, prior to the complete delivery of the beverage. The first extraction pressure is higher than the second extraction pressure so that a greater amount of foam is created upon delivery of the beverage from the first capsule as compared to that created by the second capsule. This allows a user of the system to select a cartridge that produces a beverage with the desired foam content.

The present invention relates to a method for delivering beverages from capsules designed to be extracted under pressure and containing a substance for the preparation of a food product such as a beverage.
Cartridges designed to be extracted under pressure and containing a substance for the preparation of a beverage exists on the market. They provide convenience in operation as well as reproducible extraction conditions, and they ensure freshness of the substance contained therein. This ensures the delivery of beverages of constant quality. European Patent EP 0512468 discloses one such cartridge. That cartridge is intended to be inserted into an extraction system, in which it can be injected with a fluid and opened against a supporting part of the system comprising raised elements under the effect of the pressure of the fluid entering the cartridge. The problem with this cartridge is that the beverage extracted from the cartridge runs over this supporting part and through ducting means, which means that it is difficult due to contamination and taste reasons, to envisage extracting with this system cartridges containing substances other than roasted ground coffee, because of the beverage residue present on the support.
Nestec SA's co-pending International patent application PCT/EP03/00384 filed 16 Jan. 2002 relates to a new type of capsule which does not have this disadvantage, that is to say, the capsule which can contain a wide variety of substances to be extracted as needs be, and which allows preparation and outflow of the beverage without there being a need for the beverage at any time to come into contact with any other parts of the system. The capsule of this co-pending International application is designed to be extracted under pressure, and it comprises a closed chamber containing the substance and means for allowing the capsule to be opened after the beverage is formed, at which time of use the beverage is allowed to flow out of the capsule. Opening of the capsule is achieved by relative engagement of the opening means with a retaining part of the closed chamber and the relative engagement is performed under the effect of a rise in pressure of the fluid in the chamber.
One principle of this invention lies in the fact that each capsule comprises its own opening means activated by the rise of pressure of the fluid introduced into the capsule at the time of its extraction. Another principle of this invention lies in the fact that the capsule has its own outflow passage with its own ducting means making it possible to avoid, or at least the very least considerably reduce, contact with the elements of the system or of the extraction device.
A result of these principles, taken alone or in combination, is that it is possible one after the other, to extract substances of different types or varieties without prejudice to the taste and without the risk of cross-contamination. The capsules can thus contain substances of very diverse nature and/or variety capable of being extracted or dissolved in water. It is thus possible to envisage any substance that is infused and any soluble substance: it must be clearly understood that both for extraction or for infusion or dissolution, the liquid element is hot, cold or warm water. The present invention now recognizes these advantages over the art and has implemented them in a new system and method.

System and method for dispensing beverages having different foam levels from capsules


A drum idle rotation is executed by the timing before printing on the basis of the number of drum idle rotating times selected by the operator, or the number of drum idle rotating times is set in accordance with a print image kind or a drum count value and the drum idle rotation is performed by the timing before printing on the basis of the set value. The number of drum idle rotating times by the timing before printing is corrected by a print density or an apparatus environment. Defective exposure or generation of a lateral stripe due to oligomer which is generated in the portion where a developing roller or a photosensitive drum is come into contact is prevented.

1. Field of the Invention
The invention relates to an image forming apparatus such as an electrophotographic printer having means for certainly preventing print dirt even if the apparatus is in a stationary state for a predetermined period.
2. Related Background Art
Generally, in an image forming apparatus such as an electrophotographic printer or the like, a photosensitive drum comes into contact with a charging roller and is, then, charged, an electrostatic latent image is written onto the photosensitive drum by an exposing unit, a toner image is formed onto the electrostatic latent image by a developing apparatus comprising a developing roller, a developing blade, and the like, and the toner image is transferred onto a print medium by a transfer apparatus comprising a transfer roller and a transfer belt, thereby printing.
The toner remaining on the photosensitive drum after the transfer is collected by pushing a cleaning roller or a cleaning blade of a cleaning apparatus onto the rotating photosensitive drum (for example, refer to JP-A-07-56491).
Most of the image forming apparatuses such as an electrophotographic printer and the like use a contact type developing system in which a developing roller constructed by forming a rubber elastic layer onto a conductive shaft comes into contact with a photosensitive drum by a predetermined pressing force and toner is developed.
However, in the conventional image forming apparatuses, there is such a problem that in a portion where the developing roller comes into contact with the photosensitive drum (hereinbelow, such a portion is referred to as a nip portion), since they are always in the contact state, if they are left for a long time without executing printing, low molecular components (hereinafter, referred to as "oligomer") precipitated from a rubber material of the developing roller are deposited onto the photosensitive drum, so that no dot can be formed due to defective exposure in a halftone image in a 1-by-1 mode or a 2-by-2 mode in the first printing. There is also such a problem that since a lateral stripe is formed, quality of the print image deteriorates (hereinafter, such a state is referred to as an "oligomer line").


One of a plurality of cars (17, 18) traveling in a hoistway (10) of an elevator system (9) may be diverted to the hoistway overhead (31) or pit (36) to enable another of the cars to gain access to a floor near or at a terminal floor (11, 14). When such car is at its last stop with doors open, visual (40) and audible (41) indicators present (57, 58) messages to the effect that this is the last stop and passengers should exit. After car doors are closed (66), visual and audible messages (68, 69) relate to the car going to the pit or overhead and that passengers may push any button (to reopen doors). Thereafter, the car moves (75, 76) to the overhead (31) or the pit (36) and presents (82, 83) visual and audible messages to the effect that passengers did not exit at the correct floor and must wait while the other car makes a stop. Once the terminal floor is clear, the diverted car will run (87-89) to that floor, presenting (92, 93) visual and audible messages to the effect that passengers should exit once the doors are open and reenter their service requests.

In elevator systems having a plurality of cars in a single hoistway, the traffic capacity exceeds that of elevator systems having a single car in the hoistway. However, in order to utilize this extra capacity, the cars must all be used effectively. In order for a car that is other than the highest or the lowest car in the hoistway to provide requested service at either the upper terminal floor or the lower terminal floor, respectively, the uppermost or lowermost car, respectively, must move either to the hoistway overhead or the pit in order to provide access to the other car. If passengers are lingering in a car which is at a terminal floor and is about to move to the pit or the overhead, it is preferred that such passengers leave the car and reenter their calls for service to their original destination. If however, the passengers do not leave the car as it moves to the pit or the overhead, then it becomes obvious that the passengers have traveled to the wrong place, and missed their desired destination.

Communicating to elevator passengers re car movement to pit or overhead


It is disclosed a compound of formula (I), or a pharmaceutically acceptable salt or solvate thereof:

The tumor microenvironment (TME) has become a major concern of cancer research both from a basic and a therapeutic point of view. Understanding the effect of a signaling pathway and thus, the effect of its targeting by also considering every aspect of the microenvironment, is a prerequisite to predict and to analyze the effectiveness of a therapy. Different mechanisms contribute to intratumor heterogeneity, including genetic mutations, the microenvironment and the existence of subpopulations of cancer cells with increased renewal capacity which are referred hereto as cancer stem cells. In fact, cancer stem cells refer to a subpopulation of stem-like cells within tumors which exhibit characteristics of both stem cells and cancer cells.
In general, similar to normal stem cells, cancer stem cells have self-renewal and multi-directional differentiation functions, and, under certain circumstances, they will re-initiate the cell cycle to proliferate and to generate additional tumor masses that lead to tumor recurrence. Therefore, the presence of cancer stem cells has been identified as an important cause of tumor recurrence and metastasis. At present, there is still a lack of specific antitumor drugs for cancer stem cells, and research on drugs targeting cancer stem cells is necessary.
During clinical treatment, the cancer stem cells that contribute to recurrent tumors are highly resistant to traditional antitumor drugs, which causes serious interference for subsequent treatment. Cancer therapy is primarily hindered by recurrence and chemo/radio-resistance (i.e., tumors not responding or resistant to chemotherapy and/or radiotherapy). Accumulating evidence has suggested that cancer stem cells, which initiate and maintain tumor growth, are a small subset of tumor cells. Cancer stem cells are thought to cause tumor relapse, metastasis and chemo/radio-resistance, and have been identified in many types of solid tumors, including pancreatic, breast, lung and liver tumors.
Traditional chemotherapy eliminates the bulk of tumor cells but cannot eradicate cancer stem cells, which have enhanced cell repair and cell renewal abilities (Clarke M F et al. Cancer Res. 2006 Oct. 1; 66(19):9339-44. PMID: 16990346). Due to their self-renewal ability and therapy resistance, cancer stem cells are considered the root cause of tumorigenesis, progression, drug resistance and recurrence (Chang J C et al. Cancer stem cells: Role in tumor growth, recurrence, metastasis, and treatment resistance. Medicine (Baltimore). 2016 September; 95(1 Suppl 1): S20-5. doi:10.1097/MD.0000000000004766. PMID: 27611935). Previous studies have found that cancer stem cells are enriched after chemotherapy (Li X et al. J Natl Cancer Inst. 2008 May 7; 100(9):672-9. doi: 10.1093/jnci/djnl23. PMID:18445819). Multiple signaling pathways are abnormally activated in cancer stem cells and, therefore, targeting cancer stem cells is a more effective approach for treating cancer. Evidence have shown that abnormalities in different signaling pathways exist in cancer stem cells, including the Notch, Hedgehog (Hh), and Wnt pathways, which play vital roles in embryonic development and differentiation of normal stem cells. In addition, the TME releases cytokines that increase activation of these signaling pathways to enhance the cancer stem cell population (Bocci F et al. Proc Natl Acad Sci USA. 2019 Jan. 2; 116(1):148-157. doi: 10.1073/pnas.1815345116. PMID: 30587589).
Cannabis has long been known to limit or prevent nausea and vomiting, lack of appetite, and pain. For this reason, cannabinoids have been successfully used in the treatment of some of the unwanted side effects caused by cancer chemotherapy. Besides their palliative effects, research from the past two decades has demonstrated their promising potential as antitumor agents in a wide variety of tumors. Therefore, in addition to such palliative applications, some cannabinoids have also shown anticancer properties.
As widely reported in the last decades, some cannabinoids are able to modulate different cellular signaling pathways implicated in cancer cell proliferation, migration, or death. Even though the underlying mechanisms are not totally unrevealed, there is significant evidence for the involvement of at least four mechanisms: direct inhibition of transformed-cell growth through the suppression of mitogenic signal, induction of apoptosis, inhibition of tumor angiogenesis and inhibition of metastasis for, at least, some cannabinoids (Velasco G et al. Curr Oncol. 2016. 23(2): S23-32. doi: 10.3747/co.23.3080. PMID: 27022311). So far, only few clinical data on the efficacy of cannabinoids as anticancer agents have been provided (Ladin D A et al. Front Pharmacol. 2016; 7:361. doi: 10.3389/fphar.2016.00361. PMID: 27774065).
The plant-derived family of cannabinoids is exemplified by the phytocannabinoids: tetrahydrocannabinol (−)-Δ9-THC), cannabidiol (−)-CBD and cannabigerol (−)-CBG the three main components of Cannabis sativa. Varin cannabinoids as cannabigerivarin (CBGV), tethahydrocannabivarin (Δ9-THCV), or cannabidivarin (CBDV), are derived from the corresponding varin acids: cannabigerovarinic acid (CBGV-A), tetrahydrocannabivarinic acid (THCV-A), or cannabidivarinic acid (CBDV-A). Cannabinoids have side-chains made up of five carbon atoms, whereas varin cannabinoids have side-chains made up of three carbon atoms (Hanuš L O et al. Nat Prod Rep. 2016; 33(12):1357-1392. PMID: 27722705).
Reports on anticancer effects of phytocannabinoids mainly have been focused on the activity of Δ9-THC, CBD, Δ9-tetrahydrocannabinolic acid (Δ9-THCA), cannabidiolic acid (CBDA), CBG, and cannabichromene (CBC) (Morales P et al. Front Pharmacol. 2019. 10:621. doi: 10.3389/fphar.2019.00621. PMID: 31214034). Also, cannabigerovarin (CBGV) has been studied in vitro for its anti-leukemic activity but not in solid tumors (Scott K A et al. Anticancer Res. 2013 33(10):4373-80. PMID: 24123005). The anticancer effects of Δ9-THC have been tested in different cell lines of prostate cancer, breast cancer, colon cancer, pancreatic cancer, lymphoma, lung cancer, glioblastoma, and myeloma, among others. Intracellular signaling through CBR has been shown to play an important role in these anticancer effects, involving complex signal transduction pathways through the ceramide pathway and/or the P13-K and ERK pathways. The non-psychoactive cannabinoid CBD revealed proapoptotic effects in different cancer cell lines and several molecular targets have been suggested as responsible of those proapoptotic effects, such as the COX-2, 5-LOX, PPARγ, mTOR, and p38 MAPK pathway (Hinz B et al. Br J Pharmacol. 2019; 176(10):1384-1394. doi: 10.1111/bph.14426. PMID: 30019449). On the other hand, Δ9-THCV and CBDV are being assessed for the treatment of glucose intolerance in diabetic patients and in adult epilepsy, respectively.
However, none of those treatments are linked to cancer stem cells nor have been proven useful in reducing the causes of tumor recurrence, chemo/radio-resistance and metastasis. Since cancer stem cells are precisely linked to tumor relapse, metastasis, and chemo/radio-resistance, there is currently the need to develop novel therapies to suppress cancer stem cells, including both cancer stem cell self-renewal, as well as cancer stem cell proliferation and accordingly, to develop novel therapies that suppress tumor development, metastasis and chemo/radio-resistance specifically promoted by cancer stem cells.

Cannabinoids for use in suppressing cancer stem cells

Abstract: wherein R1 is a linear alkyl group of 3 or 5 carbon atoms, and R2 is:

Abstract: and a pharmaceutical composition comprising the same, for use in the treatment of a disease whose treatment benefits from inhibiting or reducing Notch1 expression levels in cells, and/or benefits from inhibiting or reducing Notch1 levels in cells, and/or benefits from inhibiting or reducing Notch1 signaling dependent proteins levels in cells.As a consequence, present invention also relates to said compound of formula (I), and to the pharmaceutical composition comprising the same, for use in suppressing cancer stem cells, as well as, for use in reducing solid tumor development, metastasis or chemo/radio-resistance, promoted by cancer stem cells.


A vaporised flow quenching reactor for producing a fine-powder from one or more reactant materials. The reactor comprises a first heat source selected from one of a DC plasma torch and RF plasma torch, a first reaction chamber within which energized reactant materials react and a first convergent-divergent nozzle for quenching the heated reactant materials from the first reaction chamber. The reactor also comprises a second reaction chamber provided for congregation of nano particles formed therefrom and a second convergent-divergent nozzle to deliver the nano particles to a collection chamber.

Nano structure science and technology is becoming a field of technology important to the economy. Nano particle production and its application is becoming a key aspect to old and emerging technology as more and more development to nano powder is occurring. Nano particles are a technology enabler having application in a vast array of industrial, domestic and commercial situations. For example nano particles are able to be utilised as a coating material to improve the wear resistance, the transparency and ultraviolet absorption as a coating to material. Nano particles can be used in the semiconductor industry to improve the polishing process of semiconductor components to achieve a high quality output. Nano particles are also utilised to increase the variety of gases that can be detected by a gas sensor as a result of increasing sensitivity. Nano particles can also be used in paint, cosmetics, and tooling industry. Nano particles have also found a place in the medical field and are utilised to enable drug delivery.
Nano particles have been classified as particles of a size less than 100 nm. It is at a particle size below 100 nm that such particles have displayed novel chemical and physical properties which in particle sizes above 100 nm are not (or are not as prominently) displayed by the material of the same or similar chemical makeup.
As a result of the small particle size a nano powder consisting of nano particles does not need to be heated to a temperature as high as larger particle size powder in order for it to be reactive for example for the coating of other products. There is accordingly an energy saving that can be provided by the use of nano powder thereby lowering the costs of the application of such materials to other materials. This is however only an extremely small part of the advantages due to its nano-size when used for spraying. The biggest advantages come from its very large relative surface area so that the material properties are dominated by surface properties instead of normal/classical bulk property.
The nano particle production industry currently utilises two distinct processes or a hybrid of such distinct processes. The first process is commonly known as the physical/dry process. The physical/dry process involves the subjecting of a precursor feed material or materials to an energy source.
The physical/dry process includes heat and mechanical energy as an energy source. The heat source is used to evaporate the precursor material or materials (referred to as the primary elements or compounds) and then reacts with secondary elements or compounds, if necessary to form the desired output compound. The heat source may include plasma, laser, flame, hot-box or oven, etc. The primary purpose of the heat source is to evaporate and dissociate the feed stock and provide necessary conditions for the subsequence reactions to carry out the synthesizing processes. The various heat sources have certain properties that may not be available by others. For example, laser provide clean environment but the cost of operation is high. Flame or a hot box provides an inexpensive heat source but is limited by its achievable temperature and cleanliness. A plasma heat source will provide a relatively inexpensive yet clean heat source.
Mechanical processing to create nano particles are also known and such can include a ball mill or grinding device as for example referenced to in U.S. Pat. No. 3,937,405. In mechanical processing the impact of the particles with like particles results in a reduction in particle size. Milling elevates the energy of the particles which both breaks down the particle size and allows for solid chemistry energisation for conversion of a compound to occur. Likewise U.S. Pat. No. 3,602,439 describes the use of a supersonic jet mill for producing extra fine and uniform powder from a precursor material by pulverising the material by mutual collision and friction of the material in a supersonic jet stream.
The second process technique for the creation of nano particles is a chemical/wet process which utilises the careful control of an environment to cause a reaction at the ionic level. Chemical processes known to those in the industry include colloid chemistry, sol-gel processes, precipitation processes such as hydrolysis or hydrothermal processes and micro emulsion.
Existing nano particle production devices which use a plasma source to evaporate material, pass the heated reacted gases and particle product through a convergent/divergent nozzle. The primary purpose of such a nozzle is to encourage the cooling of the particles that have been generated by their being subjected to the plasma energy source. The divergent part of the nozzle results in a decrease in pressure of the flow stream with a resultant reduction in stream temperature. Such cooling is known as adiabatic cooling. U.S. Pat. No. 4,484,943 describes such a nozzle.
Plasma energy is also known to be useful in production of reactive powder. For example particle spraying apparatus utilise a plasma source for generating the energy to create a high temperature sufficient to react the precursor material for the generation of small particles. They generally use a plasma screen which comprises of an arrangement for striking an electric arc between a pair of electrodes. A gas under pressure is passed between the pair of electrodes and through the arc to be passed through a nozzle. In a plasma arc torch of a non-transfer kind (unlike a transfer kind often utilised for cutting and welding) an arc is struck between a rear electrode (commonly a cathode) and a forward electrode that forms the exit nozzle of the plasma stream.
The common form of such non transfer torch, is a DC-plasma which is mainly used and has application for thermal spraying coating. The 'exit nozzle' serves the purpose to increase the velocity of the flow to achieve a good coating. U.S. Pat. No. 5,901,551 describes a torch where a jet nozzle has provided at its inlet a plasma generating electrode. The exit nozzle serves the purpose of accelerating the flow to high speeds such as to supersonic speeds.
U.S. Pat. No. 5,111,656, U.S. Pat. No. 5,640,843 and U.S. Pat. No. 5,901,551 disclose an arc jet nozzle through which the flow of fluid is a vortex flow. It has been identified in for example U.S. Pat. No. 5,901,551 that the purpose of the vortex is to enhance efficiency of the nozzle. The nozzle is used for the provision of thrust to the material stream passing therethrough. The nozzle described in U.S. Pat. No. 4,911,805 is mainly to accelerate the fine particle to high speed and strike onto the second material (target or substrate) and create coating. Commonly such nozzles are used in spraying technology and are used to control the flow stream and the velocity of the stream. Nozzles of spraying technology are not used for the cooling down of the particles flowing therethrough thereby inhibiting their growth and their inelastic collision capabilities such as required for sintering and do not endeavour to slow down or stop the flow and reaction of particles. This is not the objective of nano particle production.
Furthermore such nozzles are provided at the source of the plasma arc and do not include an intermediate reaction chamber between the plasma arc and the nozzle where the plasma subjected precursor feed material is able to react. Usually the vortex is provided for the purposes of enhancing the mixing of the gases, to create greater path length and also more uniform discharge to increase electrode lifetime. Increased lifetime results from the movement of the arc root (being a point discharge) by the vortex flow. If the arc root location does not change, the electrodes are easily pitted and hence shortened in life. The vortex through the arc jet nozzle will ensure the arc root moves from place to place and also stabilises the arc column. Hence the vortex is not used in cooling of the flow but to ensure the arc roots move from place to place and also stabilized the arc column.
Plasma torches come in the form of a DC/AC plasma torch which is a high power and high temperature device useful for the purposes of ensuring that high melting temperature materials can be subjected to sufficient energy to ensure that the precursor stock feed (often of a particulate or powder size) can be sufficiently softened/moltened and/or vaporised and accelerated to high velocities by the plasma device. Other forms of plasma torches include the RF plasma torch which is a lower energy density unit. RF (radio frequency) plasma provides cleaner but lower energy density plasma when compare to DC (direct current) plasma.
Current nano powder devices generally operate at supersonic speeds through the expansion nozzle. Operating at supersonic speeds provides for good quenching characteristics. High quenching characteristics of a nozzle is important in making small sized particles. There is a direct relationship between the degree of quenching and the resultant size of the particles. If less efficient quenching occurs through a nozzle the particle sizes will be larger i.e. the better the quenching the smaller the particle sizes. The degree of quenching may also be resultant in other characteristics such as particle shape or chemical makeup. As is well known in physical particle chemistry, particles colliding with each other in an elastic manner do not react to engage with each other however in an inelastic manner, particles colliding with each other will encourage particle growth. However for inelastic growth, particles need to have reached a certain kinetic energy. There is a minimum threshold energy level that is required to be achieved before particle growth will occur. Such minimum threshold energy level varies for different materials. As a result many nano powder production devices currently available are designed and set up for the production of one particular type of powder. Reaction chambers and nozzle shapes and speeds therethrough are setup particular for the production of specific nano particles. The degree of cooling also has a potential to change the resultant morphology of a particle as quenching rate will affect the material crystal growth. Very fast quenching will result in amorphous, non-crystal structure, material. However a problem exists with the volume of material that can be put through a convergent/divergent nozzle at supersonic speeds. This problem relates to the choking of the flow at supersonic speeds. Choking is a common phenomenon of supersonic flow nozzles. Whilst supersonic flow nozzles present great quenching characteristics, the total heat transfer is limited as a result of a reduced flow rate that can be put through the supersonic nozzle because of the choking phenomenon.
In order to achieve supersonic flow speeds, based on 1-dimensional flow with adiabatic expansion:
M2=(u/a)2={(P0/P)[(γ−1)/γ]−1}[2/(γ−1)] where u is the velocity of the fluid; a is the local acoustic velocity at the outlet; P0 is the upstream chamber pressure and P is the downstream chamber pressure; and γ is the ratio of specific heats of the fluid; and M (mach number) exceeds 1 (supersonic) when ratio P0/P is greater the critical ratio of pressure (>2 for ideal gas where γ=1.67). Similarly, the throat area is also governed by
A/A*=(1/M){[2/(γ+1)][1+M2(γ−1)/2])}[(γ+1)/2(γ−1)] where A and A* are the of diverging outlet and throat cross-section area.
In order to achieve high quench rate, the A/A* should be high and hence the throat cross-section is small that leads to constrain for the higher flow-rate.
U.S. Pat. No. 5,749,937 describes the use of a nozzle as a quencher which moves the material within the stream outside the "reaction threshold region" or sometimes called the "threshold thermal energy" for the purposes of titanium powder production from TiCl4. U.S. Pat. No. 5,749,937 however does not make reference to nano sized particle. U.S. Pat. No. 5,749,937 furthermore describes the additional gas injection as part of a reactant gas mixture for the purposes of completing the reaction but such occurs after the throat and downstream of the nozzle. Such additional gas injection is provided to avoid the back reaction by cooling the flow stream.
A further technique involves in the creation of nano particles is the forming of a powder both in the form of an alloy or in the form of a coating, also known as packaging. U.S. Pat. No. 4,687,611, U.S. Pat. No. 4,533,383, U.S. Pat. No. 4,484,943 and U.S. Pat. No. 5,093,148 describe the formation of such. U.S. Pat. No. 4,533,393 describes an alloying application of nano powder technology. U.S. Pat. No. 4,533,383 has the reaction of the two materials to be alloyed occurring downstream of the divergent/convergent nozzles. Synthesis occurs at the collision zone of the two flow streams after the nozzles. U.S. Pat. No. 4,484,943 is absent of reference to the use of a plasma jet for reacting with raw material. Furthermore only one heat source to heat the propellant gas, in this case nitrogen, is provided.
Packaging of small particles is described in U.S. Pat. No. 4,617,055. Two in series reaction chambers are described but again there does not appear to be a disclosure of two separate heat sources of a plasma jet kind. U.S. Pat. No. 4,617,055 describes a hotbox type heater for vapourising materials and this has the inherent disadvantages of contamination and temperature control hence affecting the output material. Commonly hotbox heaters are difficult to scale up as their heating elements are the limiting factor. Such are hence commonly used for batch production only. Furthermore, no ionisation occurs which is a phenomenon of plasma heating. As such the choice of raw materials is also more limited for hotbox type power producing machines.
In the two method as shown in U.S. Pat. No. 4,617,055, the second chamber is used mainly for controlling the chamber pressure ratio to achieve expansion cooling and control condensation temperature. A further method described in U.S. Pat. No. 4,617,055 is a series operation which has a lot of limitations such as the controlling of the second material evaporation and reaction with the first material, due to the hot box heating method. Another limitation seems to be that the operation of the first chamber is at 0.05 atm. The second chamber nozzle is fed by the first nozzle and the second furnace. Gas fed into the second chamber pressure has to be lower than the first chamber pressure in order to achieve the desired cooling rate. As the first chamber is running at 0.05 atm the second chamber pressure will have to be lower and hence limit the production rate and flexibility of operation. The reason the first chamber operates in such low pressure is due to the evaporation process for the hot box.
As a consequence the prior art known to the inventor has significant limitations in the types of materials that can be processed and produced as well as flexibility in adapting a particular device for the production of different sized, characteristic and/or compositions of materials. Known nano particle production devices are set up substantially permanently for the production of a particular nano particle which thereby limits the application that a particular device has and can result in a costly exercise in reconfiguring a machine for the production of different nano particles.
Accordingly it is an object of the present invention to provide a fine particle powder reactor and/or related process which has flexibility to allow for production of a number of alternative particles of varying composition or to at least provide the public with a useful choice.
It is also an object of the present invention to provide a quenching nozzle with improved efficiency over the prior art nozzles or at least provide the public with a useful choice.


An electronic device includes a current source for applying current, a pull-up resistor or a pull-down resistor configured to be connected to one of a plurality of data terminals, a voltage level detection circuit configured to detect voltage values of the plurality of data terminals, and a connected device determination circuit configured to determine a type of a power source device based on the voltage values of the plurality of data terminals detected by the voltage level detection circuit.

1. Field of the Invention
The disclosures herein generally relate to an electronic device that is connected to a power source device that includes a power terminal, a ground terminal, and a plurality of data terminals, and a method of an electronic device for determining a type of the power source device.
2. Description of the Related Art
These days, portable devices powered by a rechargeable secondary battery (for example, portable phones, music players and game devices) are becoming popular. Among the portable devices, those are known that have a USB (Universal Serial Bus) interface and charge the secondary battery using power obtained through the USB interface as described in, for example, patent document 1.
In the case of charging a secondary battery through a USB interface, available power is specified in the USB-IF Battery Charging Specification, and the available power can be determined by performing a specified negotiation process.
These days, however, there is a case where a power level that is specified when operating a portable device is inadequate. And so, in the portable device side, ideas for determining a power level that is provided by a connected power source device have been created. In patent document 2, for example, it is described that a voltage of a data line of a USB interface, to which a power source device is connected, is divided, and that a voltage level that is provided by the power source device is determined from the divided voltage.

Electronic device and method of electronic device for determining power source device


A turbine bucket for a turbomachine includes a main body portion having a base portion and an airfoil portion, the base portion includes a bucket cavity forward region and a shank cavity. The turbine bucket also includes a cooling channel that extends through the main body portion. At least one flow passage extends between one of the cooling channel and the shank cavity, toward the bucket cavity forward region. The at least one flow passage delivers a flow of cooling gas toward the bucket cavity forward region. The flow of cooling gas limits ingestion of hot gases into the bucket cavity forward region.

Exemplary embodiments of the present invention relate to the art of turbomachines and, more particularly, to a turbine bucket for a turbomachine.
In gas turbines, an axial gap exists between a trailing edge of an upstream nozzle side wall, and a leading edge of a downstream bucket platform. Hot gases exit upstream nozzle passages and pass over the axial gap before entering bucket row passages. A portion of the hot gases becomes stagnate at leading edge portions of the bucket platform. The stagnate flow or bow wave generates a circumferential pressure gradient at the axial gap. The circumferential pressure gradient generated by the bow wave drives hot gases to the axial gap and into a trench cavity area and may even reach a wheel space cavity area. The hot gases mix with cool purge flow passing through a wheel space portion of the turbine, travel circumferentially, and exit the trench cavity at a circumferential low pressure region. Hot gases reaching lower portions of the wheel space may cause damage and lower an overall operational life of the turbine. Increasing the cool purge flow to combat the detrimental effects of the hot gases lowers turbine efficiency.

Turbine bucket for a turbomachine and method of reducing bow wave effects at a turbine bucket


Fluorescent monomethine cyanine complexes rigidized by a two-carbon alkyl group between the nitrogen's of the cyanine's heterocycles are provided and have the structure ##STR1## wherein R.sub.1 through R.sub.7 represent various selected groups or ring structures that may be chosen to provide desired solubility, reactive, or spectral properties.

1. Field of the Invention
The present invention relates to chemical dyes which can be used as fluorescent markers. The present invention particularly relates to fluorescent monomethine cyanine-based compounds which have been sterically rigidized by the inclusion of a bridging two-carbon alkyl group between the compound's heterocyclic groups and which may be chemically modified to include chemical moieties to allow the compounds to covalently or noncovalently associate with a material to thereby impart fluorescent properties to the material.
2. Description of the Invention Background
Fluorescent dyes are generally known for imparting fluorescence to biological and nonbiological materials and have been used to detect various biological or other materials by procedures such as fluorescence microscopy, fluorescence immunoassay techniques, and flow cytometry. The primary advantages of fluorescent dyes compared with dyes detectable only through light absorption include (i) the emission of light by fluorescent dyes at a wavelength different from their excitation wavelength; (ii) the greatly enhanced detectability of fluorescence emission compared to light absorption; and (iii) the generally minimal level of background fluorescence in most biological materials.
A common method for labeling biological and nonbiological materials with fluorescent dyes is to create a fluorescent complex through covalent bonding between groups on the dye molecules and compatible groups on the material. In this way, materials such as, for example, cells, tissues, amino acids, proteins, antibodies, enzymes, drugs, hormones, nucleotides, nucleic acids, polysaccharide, and lipids may be chemically labeled and quantified or may be used as fluorescent probes that bind specifically to target materials (genetic sequences, haptens, antibodies, analytes, etc.) that are to be detected by fluorescence methods. Polymer particles, cells, and other materials labeled with fluorescent dyes can also be used as fluorescent standards in flow cytometers, imaging microscopes, and other fluorescence-based detection equipment. Minute fluorescent polymer particles can also be used as labels in immunofluorescence tests, toxicology testing, and analysis of genetic sequences. Because of their utility in research and medicine, a large market has developed for fluorescent reagents including prepared protein, antibody, and nucleic acid, and other probes pre-labeled with detectable fluorescent or fluorescent dye compounds.
Because most dye molecules are either nonfluorescent or only weakly fluorescent, available fluorescent dye markers have been derived from a relatively limited number of fluorescent aromatic structures. New fluorophores with optimal properties are rarely developed. Two common classes of fluorescent dyes are those derived from the fluorescein and rhodamine chromophores. Fluoresceins fluoresce green light whereas rhodamines fluoresce in the green-orange and red regions of the spectrum. The rhodamines are difficult labeling reagents to use, are not particularly fluorescent when bound to proteins, and often cause the precipitation of the labeled protein when the dye-to-protein ratio is greater than 2:1. One particular fluorescein dye, fluorescein isothiocyanate ("FITC"), and its conjugates, enjoy wide acceptance primarily because they have a relatively high extinction coefficient and have a high quantum yield. (Quantum yield is generally related to a molecule's rigidity or planarity and indicates the molecule's propensity to fluoresce, i.e., give off energy as light, rather than give off heat when energy is provided to the molecule.) However, fluorescein dyes have a number of disadvantages, including their strong tendency to photobleach when illuminated by a strong excitation source such as the lamps used in fluorescence microscopes. When a fluorescent compound photobleaches, a large percentage of the compound's fluorescence may be lost within seconds of illumination, resulting in a rapidly diminishing image. Also, when performing fluorescence assays, the loss of image through time by photobleaching makes quantifying results much more difficult and will ultimately result in a decreased ability to detect the analyte. Reagents, such as propyl gallate and p-phenylene-diamine, may retard but do not entirely eliminate photobleaching. The fluoresceins also have a pH-sensitive absorption spectrum and fluorescence yield decreases below pH 8 and the fluoresceins do not fluoresce at low pH.
Multiple fluorophores of different colors are used simultaneously in multi-parameter analyses for detecting and correlating different fluorescently-labeled materials in such procedures as flow cytometry, microscopy, chromatography and various other detection systems. In multi-parameter analyses, a number of fluorescent compounds having a binding affinity for different targets and having different maximum emission wavelengths are used to detect and quantify the sample's various targets. To reduce the overlap of fluorescence signals in multi-parameter analyses that are emitted from the target materials labeled with different fluorescent compounds, it is desirable to use fluorescent compounds with narrow absorption and emission bands.
One class of blue-fluorescing dyes, the coumarins, suffer from a number of disadvantages. For example, the coumarin-based fluorophore 7-amino-4-methylcoumarin acetate has broad absorption and emission peaks, Also, this compound has a relatively low extinction coefficient of approximately 17,000 l/mol-cm (Handbook of Fluorescent Probes and Research Chemicals, Molecular Probes Inc., Eugene, Oreg.), thereby providing a fluorescence capacity (equal to the mathematical product of the extinction coefficient and the quantum yield) of approximately one-quarter that of the present inventions' compounds. Similarly, a fluorescent labeling dye available from Molecular Probes, Inc., under the trade name Cascade Blue (having the structure shown below where R is a reactive group) has an extinction coefficient of only 29,000 l/mol-cm. ##STR2##
The cyanine compounds are now recognized as fluorescent labeling dyes. Cyanines generally include two heterocyclic groups connected by a chain of conjugated double bonds with an odd number of carbon atoms and have been used as spectral sensitizers for photographic film. Cyanine compounds are utilized as spectral sensitizers in, for example, U.S. Pat. No. 4,337,063 (Miraha et al.) and U.S. Pat. No. 4,404,289 (Masuda et al.), 4,405,711 (Masuda et al.), and British Patent No. 1,529,202 (Exekial et al.). Fluorescence is not necessary for the photographic applications in those patents and fluorescent properties are not mentioned in those patents. The utility of cyanine compounds as fluorescent dyes was discovered only recently.
Cyanine compounds known to be useful fluorescent dyes include the unrigidized, arylsulfonated cyanine compounds of U.S. Pat. No. 5,268,486 to Waggoner et al, having the following general structure: ##STR3## wherein, the dotted lines represent one to three rings having five to six atoms in each ring. R.sub.3, R.sub.4, R.sub.8 and R.sub.9 groups are attached to the rings. At least one of the R.sub.8 and R.sub.9 groups is a sulfonic acid or sulfonate group and at least one of the R.sub.1, R.sub.2, R.sub.3, R.sub.4 and R.sub.7 groups is a moiety that will react with amino, hydroxy, phosphoryl, or sulfhydryl groups. The Waggoner et al. patent relates to trimethine, pentamethine, etc., cyanines (i.e., cyanines with more than a single double bond in the conjugated chain) and which fluoresce in the green, orange, red and near-infrared regions of the spectrum. Cyanines of this type have not been considered useful covalent labels.
One class of the cyanines includes a single atom bridging the heterocycles. These compounds are referred to herein as "rigidized" cyanines because the bridging atom restricts movement of the heterocycles about the conjugated carbon atom chain. Certain rigidized cyanines have been developed for photographic sensitization. See U.S. Pat. No. 2,541,400 to Brooker et al. and U.S. Pat. No. 3,148,187 to Heseltine. These cyanines cannot be used as fluorescent labeling dyes.
A class of monomethine cyanine-type compounds having a single atom of boron bridging the cyanine's heterocyclic groups is disclosed as useful fluorescent marker compounds in co-pending U.S. patent application Ser. No. 08/474,056 entitled "Rigidized Monomethine Cyanines" filed on even date herewith, the entire disclosure of which is hereby incorporated herein by reference.
Considering the above, but for the compounds disclosed in the above co-pending application, the existing compounds recognized as fluorescent markers suffer from several disadvantages. Also, although certain rigidized cyanine complexes are known, the majority have not been evaluated for their suitability as fluorescent dye markers.
Accordingly, it is an object of the present invention to provide bright, highly fluorescent, strongly light absorbing dyes that can be used to covalently or noncovalently associate with a material to impart fluorescent properties to the material.
It is also an object of the invention to provide fluorescent markers having high quantum yields and extinction coefficients, and therefore high fluorescence, compared with available fluorescent marker compounds, and that are relativity insensitive to pH.
It is a further object of the present invention to provide fluorescent markers that are relatively photostable, have sharp and distinct absorption and emission maxima, and have relatively small stokes shifts.
It is also an object of the present invention to provide fluorescent compounds having a short resonance distance relative to the existing fluorescent cyanine compounds so that the compounds of the present invention may have maximum absorptive and/or emissive wavelengths in the blue spectral region below 500 nm.
An additional object of the present invention is to provide a fluorescent compound having a general chemical structure that is easily modified by the addition or substitution of chemical moieties to, for example, modify the compound's emissive and absorptive maxima and solubility in polar and nonpolar media, change the reactivity of the compound, and covalently or noncovalently associate the compound with a material.

Monomethine cyanines rigidized by a two-carbon chain


Fabricated components, such as plastic injection molds, forging tools and machine components formed from a fine grained, low phosphorus, high hardness, high wear resistance, high hardenability, good machineability and high polishability, low alloy steel which is suitable for applications at elevated temperatures and at room temperatures, and an alloy steel having the following composition,. ______________________________________ C .45-.60 Mn .75-.95 P .017 max S .025 max Si .15-.35 Ni .60-2.00 Cr .85-1.30 Mo .40-.85 V 0-.30 Al 0-.030 Ti .003-.020 N.sub.2 40-90 ppm ______________________________________. the S, V and Al all being present in at least a small but effective amount, said steel and fabricated parts made therefrom being characterized by austenite grain boundaries being pinned with titanium nitrides.

In the current increasingly competitive economic environment the steelmaker must provide a product which is capable of satisfactory usage in more than one application to remain competitive in the marketplace. However, this economic dictate poses substantial challenges to the skill of the steelmaker since the operating conditions in two applications are often different and consequently the required physical and chemical characteristics are dissimilar or even in conflict.
If the steel is to be used as a mold, such as a plastic injection mold where the tool's ability to take and hold a smooth surface during long production runs is important, polishability along with high wear resistance, high hardenability, and easy machineability are key requirements. However, high strength and ductility are not as critical as the aforementioned attributes and hence the steelmaker can favor enhancement of the above mentioned key operating requirements over such attributes as high strength and ductility.
If a steel is to be used as a closed die forging tool, for example, high strength, high wear resistance, high hardenability and easy machining are essential. Fatigue resistance is not an especially critical characteristic in closed die forging since a typical die block may only be subjected to, for example, 5,000-10,000 cycles per sinking during its useful life expectancy of, for example, six or eight resinks. As a consequence the steelmaker whose product is intended to be used in closed die forging can favor enhancement of the required operating characteristics of this application such as wear resistance, impact resistance and through hardenability, over ductility and polishability, as by using alloys which contribute to the required characteristics but which do not significantly enhance ductility, and thus fatigue resistance or polishability.
If the steelmaker wishes to apply the same steel to machine part applications, such requirements as high strength, high wear resistance, high through hardness and easy machining are still important, but, in addition, ductility, and consequently fatigue resistance, must be increased since machine parts, such as gear teeth, run millions of cycles. Resistance to fracture is, generally, of lesser importance in machine parts since such parts generally are not subjected to sudden, heavy shock loads of the type encountered in closed die forging and hence the steelmaker, theoretically, can conserve on elements which contribute to fracture resistance. By the same token, the ability to take and hold a high polish is not an essential characteristic.
Thus, though high hardness, high wear resistance and through hardening are required in all applications, and said characteristics along with high strength are essential in both closed die forging applications and machine parts, polishability, fatigue resistance and fracture resistance requirements differ from environment to environment, and thus the steelmaker is faced with the task of providing a single steel which is usable in distinctly different operating environments without loading the steel with alloys which would cause the cost of the steel to the user to be so high as to be uneconomical.

Fine grained ductile plastic injection molds forging tools and machine components and alloy steel therefor having a titanium nitride pinned austenitic grain structure


A free piston internal combustion engine is under the control of micro-computer, and according to the two stroke cycle principle operating. Piston retracts by a spring. A hydraulic system outputs the power. Starting method is, when the piston is held at the end of the compression stroke, some fuel and compressed air inject into combustion chamber, perform a well-mixed compressed mixture, and then ignite for a explosion so that the engine begins the normal operating cycles.

1. Field of the Invention
This invention is related to a free piston internal combustion engine and starting methods.
2. Description of the Prior Art
Free piston internal combustion engines are simple in construction and can directly convert chemical energy into various kinds of power. However, it is very difficult to start such engines thereby making it unable to be widely utilized.
As the super charge effect of two-stroke engines is not eminent, it is proposed to adopt the well-known loop scavenging method and exhaust pipe tuning method to increase the efficiency. Tuning method is suitable for free piston engines, because its operating velocity is limited to smaller range thereby making it easier to accomplish the highest efficiency.
The previous hydraulic power output system utilizes adjustable pressure output system to adapt to different output pressure demands, which is a variable pressure output system. At present, it is replaced with full power stroke output, i.e. constant pressure output system. As the actual stroke of the engine according to the present invention is not all the same, there will be automatic compensation function in a certain range of the power output. That is to say, if the load is decreased, the stroke will become longer, but vice versa. This feature is helpful for operation and control.

Free piston internal combustion engine and starting methods

9, Alley 1, Lane 8, Hong-Tao St. Hsi-Chih Town


A cleaning mechanism is provided with an arm and a drive unit. The arm includes: a holder having a shape that allows a magnetic tape touching a magnetic head to be separated from the magnetic head without wearing the magnetic tape while the magnetic tape is under tension; and a cleaning unit that can be brought into contact with the contact surface of the magnetic head that was touching the magnetic tape while the magnetic tape is separate from the magnetic head. The drive unit drives the arm to separate the magnetic tape touching the magnetic head from the magnetic head without wearing the magnetic tape while the magnetic tape is under tension, and drives the arm so that the cleaning unit comes in contact with the contact surface of the magnetic head that was touching the magnetic tape while the magnetic tape is separate from the magnetic head.

When reading and writing data, a magnetic tape device runs a magnetic tape on a magnetic head. In this instance, the magnetic head and the magnetic tape wear, and abrasion powder remains on a surface of the magnetic head. The abrasion powder deteriorates performance relating to data reading and writing on the magnetic head. The performance deterioration is recoverable by cleaning the magnetic head with a brush or the like. Cleaning of the magnetic head is often performed on demand when performance deterioration of the magnetic head is sensed during reading and writing of data. However, when performed in a state where a magnetic tape is stored (unthreaded) in a cartridge, cleaning of the magnetic head has to be performed with reading and writing of data being interrupted for a relatively long time when performance deterioration of the magnetic head is sensed during reading and writing of data. Accordingly, cleaning of the magnetic head is preferably executable even in a state where a magnetic tape is drawn (threaded) from a cartridge. Note that an operation of unthreading and an operation of threading are collectively referred to as a "threading operation". A mechanism that performs a threading operation is referred to as a "threading mechanism".
On the other hand, in order to extend a life of a magnetic head by reducing wear of the magnetic head, it is preferable to float (lift) a magnetic tape from the magnetic head during running of the magnetic tape in which no reading and no writing of data are performed (cueing of data, rewinding for taking out the magnetic tape, or the like). In order to extend lives of the magnetic head and the magnetic tape by suppressing adhesion of the magnetic head and the magnetic tape during long-time stopping of the magnetic tape (a pause of the magnetic tape or the like), it is also preferable to lift the magnetic tape from the magnetic head during stopping of the magnetic tape. Note that a mechanism that lifts the magnetic tape from the magnetic head is referred to as a "tape lifter mechanism".
One example of a technique of cleaning a magnetic head with a brush is disclosed in PTL 1. A magnetic head cleaning mechanism in PTL 1 includes a fixed gear, an arm, an idle gear, a brush drive gear, and a rotary brush. The fixed gear is attached to a running surface of a magnetic tape on a magnetic head side. The arm rotates on the fixed gear. The idle gear is rotatably attached to the arm in such a way as to mesh with the fixed gear, and rotates during movement of the arm. The brush drive gear is rotatably attached to the arm in such a way as to mesh with the idle gear. The rotary brush is attached to a rotation shaft of the brush drive gear, and a part of outer periphery of the rotary brush serves as a cleaning surface. As a result of the configuration described above, in the magnetic head cleaning mechanism in PTL 1, the rotary brush revolves around the magnetic head while rotating on the own axis, by the rotation of the arm. Thus, the rotary brush cleans a surface of the magnetic head.
Another example of a technique of cleaning a magnetic head with a brush is disclosed in PTL 2. A magnetic head cleaning mechanism in PTL 2 includes a threading arm, a magnetic head, a brush link arm, and a cam gear. The threading arm engages a leader block with a leader pin, and pulls the leader block holding the leader pin. The brush link arm has, at a tip thereof, a brush, and is rotatably supported. The cam gear is placed closer to a magnetic head side than a threader track being a carrying path of a magnetic tape, and drives the threading arm. The brush link arm is located closer to the magnetic head side than the threader track in a normal condition. When the leader block is carried to the vicinity of the leader pin, the brush link arm rotates in conjunction with rotation of the cam gear, and brings the brush into abutment with the magnetic head on the threader track. As a result of the configuration described above, in the magnetic head cleaning mechanism in PTL 2, the brush cleans a surface of the magnetic head by rotation of the cam gear.
Still other examples of techniques of cleaning a magnetic head with a brush are disclosed in PTLs 3 to 8.
In the techniques in PTLs 1 to 8, a magnetic head cleaning mechanism does not have a function of lifting, from a magnetic head, a magnetic tape threaded in a magnetic tape device, or does not function in a state (load state) where a magnetic tape is under tension. Thus, when cleaning a magnetic head, the techniques in PTLs 1 to 8 need to unthread or loosen a magnetic tape. However, in a magnetic tape device in recent years, a magnetic tape is always under tension in such a way that the magnetic tape can be immediately run, or in such a way that the magnetic tape does not deviate from a carrying path and is not damaged by components around. Therefore, the techniques in PTLs 1 to 8 each have a problem of being unable to clean a head in a state where a magnetic tape is threaded in a magnetic tape device.
One example of a technique of lifting a magnetic tape is disclosed in each of PTLs 9 and 10. The technique in each of PTLs 9 and 10 lifts a magnetic tape by a rotator or a rack pinion. However, the technique in each of PTLs 9 and 10 is a technique of lifting a magnetic tape, does not consider cleaning of a magnetic head, and needs a dedicated tape lifter mechanism.
Another example of a technique of lifting a magnetic tape is disclosed in each of PTLs 11 and 12. The technique in each of PTLs 11 and 12 lifts a magnetic tape by a tape cleaning means connected to an actuator. However, the technique in each of PTLs 11 and 12 targets a magnetic tape for cleaning, and is unable to clean a magnetic head.
One example of a technique of lifting a magnetic tape when cleaning a magnetic head is disclosed in PTL 13. An information recording system in PTL 13 includes a recording tape, a magnetic head, a tape isolation mechanism, and a cleaning device. The recording tape runs inside a case by rotation of a pair of reels provided inside the case. The tape isolation mechanism isolates the recording tape from the magnetic head in a thickness direction. In a state where the recording tape is isolated from the magnetic head, the cleaning device cleans the magnetic head with a cleaning tape while winding off the cleaning tape wound around a supply reel. As a result of the configuration described above, the information recording system in PTL 13 cleans a magnetic head without unthreading a magnetic tape.

Magnetic head cleaning mechanism and magnetic tape device


The invention regards a hearing device with two or more microphone units each having a conduit leading from a respective sound inlet in the hearing-device housing to a respective transducer, wherein the lengths of the conduits may differ without causing a difference in the frequency characteristics of the microphone units and wherein ultrasonic frequencies may be dampened, while at the same time providing higher freedom in the physical layout of the hearing device. This is achieved in that each conduit comprises a chamber and a pipe forming a resonator, and in that the frequencies of resonance (f1, f2) of the resonators are equal.

European patent EP 1 579 728 B1 discloses a hearing aid with two microphones, wherein output signals from both microphones are combined to provide directional microphone signals.
Combining signals from two or more microphones in a hearing device is often encountered in the prior art. A prerequisite for obtaining e.g. a good "figure-eight" directional microphone signal is that the frequency characteristics of the microphones match each other closely. However, the physical embedding of a microphone or electroacoustic transducer affects its frequency characteristic. Therefore, such transducers are typically embedded in equal physical environments within the hearing-device housing and with conduits of equal length leading from respective sound inlets in the housing to the respective transducers. Since the locations of the sound inlets are typically dictated by audiologic requirements, this puts undesired constraints on the physical layout of the hearing device.
U.S. Pat. No. 3,458,668 A discloses a hearing aid with two microphones, each with a conduit leading from the microphone to a respective opening in the hearing-aid housing. The conduits have different lengths. The amplitude of the sound signal reaching a microphone may be changed by changing the length of the respective conduits. In this configuration, the frequency characteristics of the microphones do generally not match each other.
US patent application 2008/013770 A discloses a microphone array with guide tubes of different lengths each leading from a respective microphone to a respective opening in the housing. A damper is placed in the shorter ones of the guide tubes to provide equal sound signal delays between the openings and the microphones. Also in this configuration, the frequency characteristics of the microphones do generally not match each other.
International patent application WO 2004/098232 A1 discloses a hearing aid with a microphone having a first tube leading sound to the microphone. In order to prevent ultrasonic sound from reaching the microphone, a second tube is connected to the first tube near the microphone. The length of the second tube is dimensioned to have the second tube function as a quarter-wavelength resonator that dampens ultrasonic frequencies. Applying these teachings to a hearing device with two microphones would constrain the physical layout of the hearing device further.
It is an object of the present invention to provide a hearing device, which does not suffer from the above problems. It is a further object of the present invention to provide a hearing device with two or more microphone units each having a conduit leading from a respective sound inlet in the hearing-device housing to a respective transducer, wherein the lengths of the conduits may differ without causing a difference in the frequency characteristics of the microphone units and wherein ultrasonic frequencies may be dampened, while at the same time allowing a higher freedom in the physical layout of the hearing device.

This patent is subject to a terminal disclaimer.

Hearing device with two or more microphones and two or more resonators having different lengths and the same resonant frequency


When an application is activated, a mobile station 10 detects external devices 20, 30, 40 as candidates for a BLUETOOTH connection out of external devices existing in the surrounding area, and presents a list of the devices to a user. When the user selects from the list an external device 20 with which a connection is to be attempted to make, a link is established by a connection procedure according to a security level described in an ADF of the application. Namely, when “high” is described as the security level, an authentication process and an encryption process requiring input of a PIN are executed prior to the establishment of the link. On the other hand, when “low” is described as the security level, a link is established without executing these processes.

1. Field of the Invention
The present invention relates to a procedure for a mobile station to make a connection with an external device while maintaining a predetermined security level.
2. Related Background Art
Conventionally, the mobile stations including cell phones can enjoy various services, using a preinstalled application program (hereinafter referred to as an "application") or an application downloaded via a network. Some of such services involve transmission and reception of various signals to and from an external device. In this case, the mobile station needs to select a reliable communication partner in order to maintain a predetermined security level during communication. For example, Patent Document 1 is a document that discloses such technology, and it discloses a technical feature of determining the propriety of connection according to a security level of a communication partner.
[Patent Document 1] Japanese Patent Application Laid-Open No. 2002-281558

Mobile station and communication control method


A toaster pastry at least partially coated with a clear coating that provides an at least partial moisture barrier on the surface of the toaster pastry.

This invention relates to a clear coating moisture barrier composition applied to the external surface of toaster pastries.
Numerous different types of edible food coatings are known. These include relatively heavy and thick coatings of various materials (e.g., bread crumbs, potato batter, tempura, etc.) as well as various flour or starch-based coatings that are usually applied as a relatively thin batter thereby forming a much thinner coating, which can be substantially transparent after application to the food substrate. The thinner coatings are then cooked, further cooked if parfried, or otherwise thermally processed. This latter type of coating is extensively used on commercially prepared french fry potatoes, where they are often referred to as "clear coats" due to their unobtrusive and, in some cases, virtually unnoticeable visual characteristic. Clear coats formulated for french fry products would not typically adhere to wheat based substrates, such as pastry or dough. In addition to coating french fry potatoes, it has been known to use "clear coats" on snack foods and convenience foods. These clear coat compositions generally improve taste, appearance, and crispness of the exterior of the coated food and increase palatability for the food substrate.
It is also known to use clear glazes on baked goods. The glazes may be applied either before or after baking. The sole purpose of these glazes is to impart shine, but they tend to become wet and sticky over time. Still other glazes have been used to impart softness to the surface of a baked good. Such glazes typically comprise ingredients such as sugar, corn syrup solids, maltodextrins, egg, and milk.
Applicants believe that toaster pastries under the brand name Pop-Tarts® by Kellogg's Company of Battle Creek, Mich., and others have been on the market since about 1964. Since that time, several problems have been associated with toaster pastries. Despite sometimes elaborate and expensive packaging, uncoated toaster pastries of the past may become dry and not fresh tasting soon after production. Conventional, uncoated toaster pastries also become drier and even less fresh tasting upon reheating. Upon placing the toaster pastry in the presence of a known food-heating device, namely a toaster, toaster oven, or the like, the little amount of moisture on the interior of the toaster pastry is lost and the exterior of the toaster pastry becomes dry and crumbly. This results in a pastry product, which is intended to be conveniently unpackaged, quickly heated, and consumed, but instead is drier and more crumbly than a fresh-baked pastry product.
Accordingly, there is a significant need for an inexpensive, easily produced, pastry product having an enhanced mouth feel and taste due.

External coating composition for toaster pastries and other pastry products


A pharmaceutical suspension dosage form comprising greater than 80 mg/ml and not more than 150 mg/ml of Cefixime and pharmaceutically acceptable excipients.

Cefixime is a semi synthetic cephalosporin antibiotic for oral administration. It was first disclosed in U.S. Pat. No. 4,409,214 by Fujisawa Corporation, Japan.
It has a bactericidal action and the mechanism of action is based on inhibition of bacterial cell wall synthesis.
It is indicated for the treatment of infections caused by various gram—positive and gram—negative organisms chiefly uncomplicated urinary tract infections caused by E. coli and P. mirabilis, otitis media caused by H. influenza, M. catarrhalis and S. pyogenes, acute bronchitis and exacerbations of chronic bronchitis caused by S. pneumonia and H. influenza. It is also indicated for uncomplicated gonorrhea caused by N. gonorrhea. It is one of the most prescribed drugs for pediatric use.
Cefixime as a drug is poorly soluble in water. From the point of view of bioavailability, the preferred form of administration of sparingly soluble medicaments such as beta lactam antibiotics is often an aqueous suspension. Cefixime, given orally, is about 40%-50% absorbed whether administered with or without food.
Children 12 years of age or younger receive, e.g., about 8 mg of Cefixime/kg of body weight each day. The recommended dose can be administered alternatively all at once or divided into 2 single doses (e.g., about 4 mg of Cefixime/kg of body weight in the morning and evening). An increase in the daily dose to 2.×6 mg of Cefixime/kg of body weight is possible depending on the severity and the location of the infection. Adults and children above 12 years of age may receive 400 mg of Cefixime each day. The recommended daily dose may be administered alternatively all at once or divided into 2 single doses (in the morning and evening). The dose should be reduced for patients with distinctly impaired renal function. Solid dosage forms such as tablets and capsules have certain disadvantages since they have to disintegrate in the gastrointestinal tract and then the medicament has to dissolve before it can be absorbed, thus leading to slower absorption as compared to that of the suspension dosage form and also the absorption is less than the suspension dosage form leading to bioequivalence issues. Also, certain patient populations such as pediatrics and geriatrics have difficulty in swallowing tablets and capsules, and there is a practical limit to the size, and therefore the dose, that can be swallowed.
The oral suspension dosage forms have certain advantages over the above mentioned dosage forms especially in population segments such as pediatrics and geriatrics who have problems in swallowing the solid dosage forms. Further The oral suspension dosage form produces average peak concentrations approximately 25%-50% higher than the conventional tablets. The area under the time versus concentration curve is greater by approximately 10%-25% with the oral suspension than with the conventional tablet after doses of 100 to 400 mg, when tested in normal adult volunteers.
U.S. Pat. No. 4,079,138 by American Home Products Corporation describe a permanent suspension with a non-aqueous basis as vehicle for active substances, which are sensitive to hydrolysis.
U.S. Pat. No. 5,776,926 by Merck discloses Cefixime compositions in the form of non-aqueous suspensions.
Cefixime is currently available in a number of different formulations in various strengths for adult and pediatric patients, for example as tablets comprising 200 mg and 400 mg Cefixime and as oral suspension comprising 100 mg/5 ml Cefixime.
In some patient population the compliance for the currently available oral suspension is low due to requirement of dosing greater than 100 mg in certain disease conditions. Lack of availability of a oral suspension dosage form comprising greater than 100 mg/5 ml cefixime leads to low compliance rates. This is due to multiple dosing required leading to low compliance rates (e.g. spillage).
There is a need to develop a higher strength oral suspension in unit dose for improving the patient compliance and for reducing the frequency of dosing.
Further there is also a need to develop a concentrated oral suspension of Cefixime which incorporates higher amount of drug per unit volume of the suspension so as to avoid multiple administration.