A telecommunications system provides a facility for mobile communications to a mobile node. A core network and a radio network are arranged to communicate the internet packets in accordance with a current configuration of routing and communications resources of at least one of the core network and the radio network. The mobile node is operable to generate a packet data connection activation request. The request is adapted to include a service level identifier representing a priority to be afforded to communicating internet packets to or from the mobile node with respect to the internet packets received from other mobile nodes. The core network is operable to adapt the current configuration of routing and communications resources of at least one of the core network and the radio network following a change of location of the mobile node with a relative priority determined in accordance with the service level identifier.

In packet radio networks such as, for example, the General Packet Radio Service (GPRS), mobile nodes are provided with a facility for communicating packet data via a radio interface and a core network. The packet radio networks are arranged to allow the mobile nodes to move within a coverage area provided by the radio network whilst supporting communication sessions.
In some scenarios, the packet radio network will be required to deal with a high volume of requests from mobile nodes for various network services, such as at peak usage times or in parts of the packet radio network covering busy areas such as city centers. The requests from the mobile nodes resulting for example from mobility or hand-over requests can affect both the radio network and the core network of the mobile radio network. These network services may be related to signaling such as routing update messages, they may relate to actual voice and/or data sessions such as telephony, web browsing or email, or they may be associated with a configuration of the packet radio network or allocation of communications resources, which is required to support mobility, such as handovers between base stations. When the packet radio network is required to deal with such a high volume of requests, it is possible that communication of data packets via the packet radio network will experience increased delays or interruptions, because limited communications resources are being allocated to the communication of a higher volume of data packets from other mobile nodes. Such increased delays or interruptions in the communication of data packets can cause a reduction in service quality particularly for mobile nodes which are engaged in supporting services requiring real time, or near real time quality of service such as, for example voice services or video conferencing. It is therefore desirable to alleviate or at least reduce such delays or interruptions in the communication of data packets across packet radio networks in order to reduce a likelihood of affecting the service quality provided to mobile nodes, particularly for those engaged in supporting services requiring real-time or near real time quality of service.

This patent is subject to a terminal disclaimer.


A power detection apparatus is provided. The power detection apparatus includes a first current processing circuit and a second current processing circuit. The first current processing circuit is configured to provide a dynamic bias voltage at a bias terminal in response to a variation of a system power. The second current processing circuit is coupled to the first current processing circuit and is biased under the dynamic bias voltage for outputting a power good signal at an output terminal to represent that the system power is ready when the dynamic bias voltage is greater than a threshold voltage.

1. Technical Field
The invention relates to a power detection technique, and particularly, to an ultra low startup current power detection apparatus which is configured to detect whether the power is ready.
2. Description of Related Art
In the modern day, electronic apparatus systems have a detection circuit to generate a signal if the system power is not ready (such as the voltage level of the system power is lower than a certain predetermined voltage value). The signal generated by the detection circuit will force the system to stop normal operations. After the power supplied to the system is ready (i.e. the voltage level of the system power is higher than the predetermined voltage value), the signal generated by the detection circuit will change it status to make the system to start operation. In some application, when the provided power level of the system is lower than the predetermined voltage value, the power consumption of the system should be as low as possible. Under such condition, other circuits of the system may be disabled in response to the signal generated by the detection circuit. Therefore, how to design a system power detection circuit with low power consumption is an important issue to be developed by related practitioner.

Ultra low startup current power detection apparatus


A scheme for providing targeted advertisements in a multicast adaptive bitrate (ABR) streaming environment. In one implementation, ads specific to a subscriber's demographic profile and relevant to the genre of a tuned MABR media channel may be downloaded in a gateway (GW) or into a network storage system. In another implementation, multicast ABR streams of ads may be triggered at specific points (e.g., insertion markers in a multicast ABR media channel) that can be selectively joined by a GW node based on demographics and channel genre. In yet another implementation, continuously streaming multicast ad channels may be switched at suitable points in a multicast ABR media channel based on targeting parameters.

With the advent of new technology, e.g., home gateways with multiple tuners and Converged Cable Access Platforms (CCAPs), and the like, managed IP video services are now becoming feasible and cost-effective. Multicast streaming of content using ABR techniques is also being exploited for developing an all-IP cloud-based approach to delivering multimedia programming. Content ingest, encoding, packaging and ways to support alternate content and advertisement insertion ("ad insertion") are also being explored.
Within the domain of conventional broadcast radio and television, the process of ad insertion into a particular broadcast is well known. Conventionally, broadcast advertisement content insertion may occur both at national network and local/regional network levels. At the national network level, advertisements are often inserted into the network feed before the broadcast content is transmitted over, for example, a particular national distribution network. At the regional network level, local advertisements may be inserted into a received national feed by, for example, the regional/local radio or TV broadcast station and such advertisements may typically replace some or all of the national network advertisements. Such local advertisements may be targeted to the demographics of the entire service area of the particular broadcast station and may advertise the local businesses, e.g., local grocery stores, restaurants, etc. Although such techniques exist in the traditional content delivery systems, it should be appreciated that there are no known advertising systems that target ads for multicast content at a granularity level as will be described below.

Advertisement targeting scheme in a multicast ABR environment based on ad caching


Adjustable transceiver circuitry is provided for programmable integrated circuits such as programmable logic device integrated circuits. The transceiver circuitry has a dynamic phase alignment circuit that can be used for aligning clock and data signals. The dynamic phase alignment circuit contains a bypassable synchronizer. Four modes of operation are supported by the transceiver circuitry including a normal source synchronous mode, a normal dynamic phase alignment mode, a soft clock data recovery mode, and a phase-locked-loop source synchronous mode. In normal source synchronous mode, the dynamic phase alignment circuit performs no phase alignment or clock rate matching. In normal dynamic phase alignment mode, the dynamic phase alignment circuit performs only phase alignment operations. In soft clock data recovery mode, programmable logic on the programmable integrated circuit is configured to perform rate matching and phase alignment. In phase-locked-loop source synchronous mode, phase alignment and board level deskewing operations are performed.

This invention relates to integrated circuits such as programmable logic device integrated circuits, and more particularly, to programmable logic device integrated circuits with dynamic phase alignment circuits.
Programmable logic devices are a type of integrated circuit that can be programmed by a user to implement a desired custom logic function. In a typical scenario, a logic designer uses computer-aided design tools to design a custom logic circuit. When the design process is complete, the tools generate configuration data. The configuration data is loaded into a programmable logic device to configure the device to perform the functions of the custom logic circuit.
In a typical system, a programmable logic device integrated circuit and other integrated circuits are mounted on a circuit board. The circuit board contains conductive paths that interconnect the integrated circuits. A system may also have paths that interconnect integrated circuits on different boards. Programmable logic devices contain transceiver circuitry for transmitting and receiving data over these communications paths.
Programmable logic device transceiver circuitry includes input and output drivers. The input and output drivers may use differential signaling schemes in which a pair of signals are referenced to each other or single-ended signaling schemes, in which signals are referenced to ground. In high-speed environments, the input and output drivers are generally differential drivers and handle differential signals.
In some programmable logic device architectures, complex transceiver circuitry is provided that supports many different operating modes. High-speed signals are handled by relying extensively on hardwired logic. While this type of arrangement may be satisfactory for some logic designs, the inclusion of complex transceiver circuitry is unnecessary for some designs and adds needless overhead. As a result, other programmable logic device architectures forgo complex transceiver circuitry and only support limited transceiver functionality such as source synchronous input-output signaling standards. Although these architectures dedicate less hardwired circuitry to processing incoming and outgoing data signals, they do not allow circuit designers to benefit from the different operating modes available with more complex transceiver architectures.
It would therefore be desirable to be able to provide integrated circuits such as programmable logic device integrated circuits with transceiver circuitry that supports a number of different operating modes without requiring the dedication of complex hardwired resources.

Programmable logic device integrated circuit with dynamic phase alignment capabilities


A method and a device for generating a CID for D2D communication are provided. A transmitting device transmits a request for direct communication between the transmitting device and a receiving device on a resource unit of a first resource index determined based upon at least one of a device ID of the transmitting device or of the receiving device during a first period, receives information about at least one used CID being used by at least one surrounding device from the peripheral device during a second period, transmits information including at least one available CID acquired during the second period on a resource unit of a second resource index being identical to the first resource index during a third period, and determines at least one CID to be used for D2D communication between the transmitting device and the receiving device based on the transmitted information.

1. Field of the Invention
The present invention relates to Device-to-Device (D2D) communication. More particularly, the present invention relates to a method and apparatus for generating Connection Identifiers (CIDs) to be used for D2D communication.
2. Description of the Related Art
With the development of communication devices and communication systems, users of the communication devices require services by which they can easily access and share their desired information anytime. Recently, the advent of smart phones and tablet Personal Computers (PCs) has offered a new environment in which users may acquire and share a variety of information over a wireless communication system. However, in the case of the wireless communication systems, users cannot acquire and share desired information unless a wireless communications infrastructure is built. In addition, due to complexity and time delay, a given wireless communication system may not be capable of efficiently providing the real-time information which may appear as minor, but is nonetheless useful in everyday life.
To address these shortcomings, Device-to-Device (D2D) service has emerged, which is performed directly between devices via a D2D communication link. The D2D link operates without certain network entities, such as base stations, in spaces that have no communications infrastructure.
A device supporting this service acquires synchronization with its surrounding devices, discovers the surrounding devices using preset resources at a preset time, and acquires device information of the discovered surrounding devices. The device information may include identification information, interest information and application information of the discovered devices.
As described above, devices supporting a D2D service perform a process of discovering surrounding devices via or using preset resources for a preset time, and generating a CID for a communication connection with other desired devices.
To provide additional support in such a D2D system, a system and method is provided for minimizing power consumption in devices supporting a D2D service, and for increasing the efficiency of generating CID in devices operating within a D2D service.
The above information is presented as background information only to assist with an understanding of the present disclosure. No determination has been made, and no assertion is made, as to whether any of the above might be applicable as prior art with regard to the present invention.

Method and apparatus for generating connection identifier for device-to-device communication


An apparatus and method for sensing temperature in an oil or gas well use an AC-cut temperature crystal connected to a Z-cut crystalline member contained in a crystalline housing that can be subjected to high pressures and temperatures.

This invention relates generally to a crystalline resonator package that includes an AC-cut crystal as a temperature sensor. Such a temperature responsive AC-cut crystal provides an improvement in a pressure and temperature transducer of the type including a crystalline housing subjected to pressure and temperature in an oil or gas well. The present invention also relates to a method of sensing temperature in an oil or gas well.
During drilling, completing and producing an oil or gas well, temperature and pressure measurements are typically taken from within the well to obtain information about the ability of the well to produce oil or gas. This can be done by lowering a quartz crystal pressure and temperature transducer into the well and generating electrical signals in response to the frequencies at which the quartz crystal members oscillate in response to sensed pressure and temperature. Typically a quartz crystal reference member is also provided for compensating for changes in response due to pressure or temperature. This reference member and the temperature sensing member can be housed together.
A pressure and temperature transducer currently used by Halliburton Services to measure pressure and temperature in an oil or gas well includes three active elements. These are implemented by quartz resonators mounted within a quartz housing made of two separate crystalline packages held adjacent each other. One of these packages contains the crystalline resonator that senses pressure applied to the housing, and the other package contains both a crystalline resonator that senses temperature communicated through the housing and a crystalline resonator that functions as a reference to compensate for temperature effects on the pressure sensing resonator. In a particular implementation, the temperature resonator is a torsional mode tuning fork (TTF) quartz crystal. See, for example, U.S. Pat. No. 4,802,370 to EerNisse et al.
Although this type of pressure and temperature transducer is suitable for many oil and gas wells, the use of a TTF temperature crystal limits the temperature range within which it can be used. A TTF crystal has difficulty oscillating at temperatures above 175 degrees centigrade (.degree. C.). A TTF crystal can also have a temporary loss in activity within the low temperature range from -10.degree. C. to -15.degree. C. due to condensation of gaseous lead tetrahydride that can form within the crystalline package when it is sealed. Special sealing techniques can be used to prevent this, but they are time consuming and expensive. Thus, there is the need for an improved temperature transducer and temperature sensing method providing an extended operating range relative to the aforementioned transducer incorporating a TTF temperature crystal.

Crystalline transducer with ac-cut temperature crystal


A method for manufacturing a printed circuit board with a capacitor embedded therein which has a dielectric film using laser lift off, and a capacitor manufactured thereby. In the method, a dielectric film is formed on a transparent substrate and heat-treated. A first conductive layer is formed on the heat-treated dielectric film. A laser beam is irradiated onto a stack formed, from below the transparent substrate, to separate the transparent substrate from the stack. After the transparent substrate is separated from the stack, a second conductive layer is formed with a predetermined pattern on the dielectric film. Also, an insulating layer and a third conductive layer are formed on the first and second conductive layers to alternate with each other in a predetermined number.

1. Field of the Invention
The present invention relates to a method for manufacturing a printed circuit board with a thin film capacitor embedded therein using laser lift-off, and more particularly, to a method for manufacturing a printed circuit board with a thin film capacitor embedded therein which has a dielectric film using laser lift off, and a printed circuit board with a thin film capacitor embedded therein manufactured thereby.
2. Description of the Related Art
With a smaller, lighter, higher-speed and higher-frequency trend of electronic devices, the electronic devices are increasingly required to possess higher-density. In reality, vigorous studies have been conducted on technologies to integrate passive and/or active devices into a substrate. Also, in ongoing researches to reduce size of the electronic devices, many passive devices such as a resistor, a capacitor and an inductor are embedded in a printed circuit board (PCB) instead of being installed thereon. Out of these passive devices, the capacitor accounts for a considerable proportion of about 60%. Thus, much attention is drawn on an embedded capacitor. As described above, the capacitor is embedded in the PCB instead of being installed thereon. This downscales size of the passive device by 40% and assures better electrical properties at a higher frequency due to low impedance (<10 pH).
The conventional embedded capacitor is disclosed in U.S. Pat. No. 5,261,153. The document teaches a method for manufacturing a printed circuit board with a capacitor embedded therein by lamination of conductive foils and uncured dielectric sheets alternating therewith. Moreover, U.S. Pat. No. 6,541,137 discloses a high temperature thin film embedded capacitor using dielectrics. Specifically, the document proposes a barrier layer for preventing the conductive layer from oxidizing from high temperature heat treatment of 400° C.□ to 800° C.
However, in this embedded capacitor, a dielectric film is necessarily made of a dielectric material having a high dielectric constant selected from a group consisting of barium strontium titanate (BSTO), barium titanate (BT), lead zirconium titanate (PZT), barium zirconium titanate (BZTO), and tantalum titanate (TTO). This dielectric material should be excellent in crystallinity to exhibit high dielectric constant. To this end, the dielectric material should be heat-treated at a temperature of 500° C. or more.
But in the conventional embedded capacitor, a thin film is formed on an electrode as an RCC type and crystallized through heat treatment to impart a certain dielectric constant to a capacitor product. Then these materials are employed in a PCB process. However, the materials need heat-treating at a high temperature of 400° C. to 800° C., and are hardly configured on a resin-containing PCB.
Dielectric properties of the thin film capacitor are greatly affected by the type of the substrate, as is apparent from FIG. 1. FIG. 1 demonstrates capacitance of a Pb-based dielectric film deposited on two types of substrates with respect to a voltage applied. A copper foil and a Pt/Ti/SiO2/Si substrate are adopted for the substrates, and heat treated in the air at 650° C. for 30 minutes. The dielectric film is deposited to a thickness of 0.6 micrometer. The dielectric film on the cooper foil exhibits capacitance of 0.2 μF/cm2, much lower than the dielectric film on the Pt/Ti/SiO2/Si substrate whose capacitance is 2.5 μF/cm2. The dielectric film deposited on the copper foil is affected by an oxidized interface resulting from oxidation of the copper foil which is heat-treated along with the substrate. This prevents the dielectric film on the copper foil from manifesting properties peculiar to the dielectric material.
Therefore, studies have been conducted unceasingly to prevent the copper foil from oxidization in two methods. That is, a heat-treatment atmosphere has been regulated or a strong oxidation-resistant nickel layer has been formed on the copper foil to deposit and heat-treat the dielectric film. These methods however entail a problem of decreased capacitance of the capacitor manufactured.
As a result, there has arisen a demand for developing a method for manufacturing a capacitor with a printed circuit board embedded therein having a dielectric film that needs heat-treating at a high-temperature through a general PCB manufacturing process.

Method for manufacturing a printed circuit board with a thin film capacitor embedded therein having a dielectric film by using laser lift-off, and printed circuit board with a thin film capacitor embedded therein manufactured thereby


Polarized light which is emitted from an optical fiber becomes circular polarized light by passing through a first quarter wave plate. The circular polarized light which has entered a second quarter wave plate is converted into nearly linear polarized light which has S polarization. P polarization components are removed from the nearly linear polarized light by a polarizer, but the polarizer is not always necessary. The optical axis of the polarizer is set to be a direction which allows transmitting of S polarized light. The light that has passed through the polarizer is separated into diffracted lights by a diffraction grating, and is used as the structured illumination light.

The present invention relates to a structured illumination microscope device and an image forming apparatus.
In the field of observation and measurement of the micro-structures of samples, observation at higher spatial resolution is demanded. As a method to improve the lateral resolution of a sample, a method of modulating a sample with structured lights during photographing and demodulating the captured image by image processing is known as "structured illumination microscopy", and is disclosed in U.S. Pat. No. 6,239,909 and U.S. RE38,307, for example.
The sixth embodiment disclosed in U.S. Pat. No. 6,239,909 is an example when the structured illumination microscope apparatus is applied to a fluorescence microscope, and the optical system thereof splits the illumination light emitted from a coherent light source using such beam splitting means as a diffraction grating, then condenses the illumination beams into a pupil plane of an objective lens, and emits the illumination beams as parallel beams from the objective lens at different angles, so as to overlap around the observation object and form an interference fringe.
Because the illumination light is modulated into a fringe, diffracted lights containing spatial frequency components of the shape information of the observation object, which cannot be transferred by a conventional imaging system, can be used for image formation. And by relatively modulating the phase of the split illumination beams and moving the interference fringe on the observation object when a plurality of images are acquired, image formation based on image computing processing is enabled.
In concrete terms, phase modulation is performed by moving the diffraction grating vertically to the optical axis, or in another example, by inserting a wedge prism into one of the illumination paths, and moving this wedge prism in a direction vertical to the optical axis.
According to the method disclosed in U.S. RE38,307, illumination light from the coherent light source is guided using an optical fiber, and is split by such beam splitting means as a diffraction grating, and then the illumination beams are condensed into a pupil plane of the objective lens so as to form an interference fringe near the observation object. Because the illumination light is modulated into a fringe, the high frequency components of the shape information of the observation object, which cannot be transferred by a conventional imaging system, can be used for image formation. And a plurality of images are captured in the same manner, and image formation based on image computing processing is performed.
According to this method, in order to create one image, not only a plurality of images are acquired with phase-modulated structured illumination, but also images are acquired with changing the direction of the structured illumination. This is because the high frequency components can be used for image formation only when the structure has the same direction as the direction of the structured illumination, so in order to restore the shape of the sample which extends two-dimensionally, a plurality of images must be acquired with changing the direction of the structured illumination, and be combined.
In this structured illumination, it is normally desirable that the beams with respect to the interference surface have S polarization in order to allow two or more beams to interfere. Because the contrast of the interference fringe when beams with S polarization is 1, regardless of the incident angle, the contrast when beams enter in the P polarization state attenuates in proportion to cos(Δθ), where Δθ is the crossing angles of the beams. Since the observed light is the sum of S polarization and P polarization, contrast to be observed decreases as P polarization attenuates. At Δθ>90°, the numeric value of the contrast of P polarization becomes negative, which means that the brightness/darkness of the interference fringe inverts, and the interference fringe generated by S polarization is cancelled, which is not desirable.
In particular, the structured illumination microscope is a technology used to obtain high resolution, and it is preferable that the NA of the objective lens to be used is as high as possible, and the pitch of the structured illumination is as short as possible. As a result, the beams for the structured illumination enter into the sample at a large angle, so if a P polarization component exists, attenuation of the P polarization is major since the above mentioned Δθ is large, which becomes the cause of deterioration of the structured illumination contrast.
In order to address this problem, a non-polarization state is created by allowing light from the light source to pass through a diffuser or vibrating multi-mode optical fibers, then light is nearly linear polarized using a polarizer, which is installed near the diffraction grating and which rotates coaxially with the diffraction grating, so as to enter with S polarization onto the sample.
As a result, ideal structured illumination contrast is obtained, but the polarizer blocks about half of the light power, which lowers utilization efficiency of the light to 50%.

Structured illumination microscope apparatus and an image forming apparatus

THE REGENTS OF THE UNIVERSITY OF CALIFORNIA


A concentrated fruit juice powder obtained by a convection current vacuum freeze drying process that includes: selecting and preparing fruits by predetermined quality guideline; extracting fruit juice by inserting the fruits into a screw press juicing apparatus having a precutter and a screw press whose body surface varies non-linearly, which is configured to achieve a maximum extraction efficiency; adding probiotics into the extracted fruit juice; freezing the fruit juice mixed with the probiotics in molds using an individual quick freezer (IQF) to obtain frozen fruit juice blocks; and vacuum freezing the frozen fruit juice blocks using a convection current vacuum freeze drying apparatus.

Fruits and plants are important diets beneficial to our health. Ambarella fruits, pennywort (Centella asianatica); pineapples; kumquats; durians; the mixture of beetroot, apple, and passion fruit; passion fruits; and soursops are all not only deliciously edible fruits and plants but also known for their medicinal benefits. Their extracted juice are not only refreshingly delicious but also have many medicinal benefits after consumption. One serving of ambarella fruit provides 48 Kcal of energy, 1 gram of protein, 12 grams of carbohydrate, 233 IU of vitamin A, 30 mg of vitamin C, 15 mg of calcium, 3 mg of iron and 22 grams of phosphorus. Ambarella fruit also contains dietary fibber and vitamin B complex constituents like thiamine and riboflavin. Other medicinal benefits of ambarella fruits include: boosting immune system, improving skin health, treating coughs, treating digestive problems, improving vision, providing energy, and helping in weight loss. More particularly, ambarella fruits are rich in vitamin C which improves the function of the immune system. They also improve the formation of collagen and accelerate the wound healing process. Antioxidants in the ambarella fruit help preventing free radical damage. In addition, the vitamin C content of the fruit helps in tissue repair and nourishes the skin. Ambarella fruit is a good source of vitamin A. It plays an important role in the visual perception. The compound of vitamin A known as retinol helps distribute images that are received by the retina of the eye. Other benefits of the ambarella fruits include: the antioxidants present in the fruit fight against cancer. It helps in the renewal of tissues and protects against cardiovascular diseases.
Pennywort—found in most tropical and subtropical countries growing in swampy areas—is clonal, perennial herbaceous creeper belonging to the family Umbellifere (Apiceae). The primary active constituents of pennywort are saponins (also called triterpenoids), which include asiaticosides, in which a trisaccharide moiety is linked to the aglycone asiatic acid, madecassoside and madasiatic acid. These triterpene saponins and their sapogenins are mainly responsible for the wound healing and vascular effects by inhibiting the production of collagen at the wound site. Apart from wound healing, the herb is recommended for the treatment of various skin conditions such as leprosy, lupus, varicose ulcers, eczema, psoriasis, diarrhoea, fever, amenorrhea, diseases of the female genitourinary tract and also for relieving anxiety and improving cognition. Pennywort also strengthens the weak veins, has antipedressant properties, antiepileptic properties: it increases the cerebral levels of GABA, cognitive and antioxidant properties, gastric ulcer, antinociceptive and antiinflmmatory properties, and radiophroection.
Coconut juice is rich in Calcium (Ca), magnesium (Mg), and potassium (K). Potassium helps keep fluid and electrolyte balance in the body, especially during exercise. Because there is more potassium than sodium in coconut water, the potassium may help balance out sodium's effect on blood pressure and possibly even help lower it. Calcium is vital for more than just strong bones and teeth. It helps muscles contract and work properly. As one exercises, his/her muscles pull on the bones and break them down slightly. As the body recovers, the bones use calcium to get stronger and repair. Magnesium helps to move calcium and potassium into muscles to aid in contraction and relaxation. It also helps with energy production and supports organ function. A hard workout can leave one person depleted in magnesium and prone to cramps, restless muscles, and spasms. In addition to all of its hydrating benefits, coconut juice contains antioxidants that help to neutralize oxidative stress and free radicals created by exercise.
Bromelain is an enzyme that is present in the pineapple juice. It helps the body break down and digest proteins. In capsule form, bromelain may reduce swelling, bruising, healing time, and pain after surgery. Pineapple juice from the core, stem, and flesh suppressed the growth of ovarian and colon cancer cells. Pineapples also provide a good quantity of beta carotene which can help reducing risk of colon cancer. Pineapple juice contains vitamin C and beta carotene. These antioxidants can help reduce wrinkles, improve overall skin texture, and minimize skin damage from sun and pollution exposure. Vitamin C also helps with the formation of collagen, which is a common protein in the body that gives the skin its strength and structure. The vitamin C content of pineapples may help preserve eye health. Vitamin C can reduce the risk of cataract progression by one-third.
Kumquats contain several unique antioxidant flavonoids (such as DGPP, margaritene, isomargaritene, fortunellin, and poncirin). Kumquat juice can break down free radicals and their antioxidant activity which increases with the flavonoid content. Vitamin C is another powerful antioxidant found in relatively high amounts in kumquats (approximately 12 mg/fruit). Kumquat juice probably can turn on PPAR-a, a protein that revs up metabolism and fat-burning. Free radical-damaged LDL triggers an inflammatory response that causes cholesterol to build up inside the arteries. Kumquats also contain phytosterols (amyrin, lupenone, and sitosterol) which interfere with its uptake in the gut. In addition, Kumquats are a source of calcium, a mineral that is essential to bone formation and health. Indeed, the flavonoid poncirin promotes the formation of the cells that build and repair bones (osteoblasts), while preventing mineral loss caused by osteoporosis. Beta-cryptoxanthin is the carotenoid found in kumquats. The body can use it to build antioxidant defense and make vitamin A. Juice enriched with beta-cryptoxanthin increased bone formation and reduced its breakdown by blocking bone-degrading cells (osteoclasts). Complex sugars isolated from kumquat blocked the pancreatic enzyme that helps digest fats in the gut.
Drinking durian juice helps prevent constipation and improves digestive health. The thiamin in the fruit may improve appetite and general well-being in the elderly. The fiber in durian fruit also stimulates peristaltic motion. It may ease the digestive process in the intestines. It also helps treat issues like bloating, excess flatulence, heartburn, and cramps. The organosulfur in durians may regulate the inflammatory enzymes and reduce the risk of cardiovascular diseases. Intake of fruit juice that are rich in soluble dietary fiber may help lower the levels of low-density lipoprotein cholesterol (LDL-C) and reduce the risk of coronary heart disease. Durian juice is a heart-friendly food with a high fiber content. The manganese (Mg) in durian may help in the maintenance of blood sugar levels. The antioxidants in durian also help reduce oxidative stress, which can otherwise aggravate diabetes symptoms. Durian also has a lower glycemic index (GI). Hence, the fruit would not lead to blood sugar spikes. Durian is a good source of potassium (K) which helps lowering blood pressure, acting as a vasodilator. Durian is rich in vitamin C. The nutrient is a powerful antioxidant that reduces oxidative stress caused by free radicals. The lower the oxidative stress levels, the slower the aging process. Durian is rich in other antioxidants that may help reduce cancer risk. The fruit contains polyphenols that inhibit cancer growth and even kill cancer cells. Since the antioxidants of durians fight free radicals, they may also help in lowering cancer risk. Durians are rich in potassium (K) and magnesium (Mg). These two minerals contribute to bone health. Durian is a rich source of folate which can promote the number of red blood cells produced. Other minerals in durian may trigger the production of red blood cells (RBC). Durian may help in the production of serotonin which helps relieving the symptoms of depression, anxiety, and stress.
Passion fruit is a flowering tropical vine, known as Passiflora, which grows in warm climates. It contains a soft yellow pulp and lots of seeds inside a hard rind. The health benefits for consuming passion fruits include: key nutrients such as vitamin A, potassium (K), magnesium (Mg), vitamin C, calcium (Ca), iron (Fe), and fiber; rich in antioxidants; good source of fiber; low glycemic index (GI); source of insulin such as piceatannol; boosting the immune system; and supporting heart health.
Beetroots can help lower a person's blood pressure because it contains anti-inflammatory compounds called betalains which inhibit specific signaling pathways that play a role in inflammatory diseases. A betalain called phenethylamine-betaxanthin reduced the activity of an inflammatory enzyme by 32 percent. Beetroots are rich in iron (Fe), an essential component of red blood cells. Without iron, red blood cells cannot transport oxygen around the body. People who have low iron levels can sometimes develop a condition called iron deficiency anemia. Adding sources of iron to the diet can reduce the risk of this condition. Beetroot juice contains antioxidants, vitamin A, vitamin B-6, and iron. These compounds help protect the liver from inflammation and oxidative stress while enhancing its ability to remove toxins from the body. Certain compounds in beetroot juice, such as nitrates and betalains, may improve athletic performance. Nitrates in beetroot can boost a person's athletic efficiency by increasing blood flow and oxygen to the muscles.
Due to its high fiber content, soursop fruit juice may aid with proper digestion. The fruit's juice can also act as a diuretic and cleanse the gastrointestinal tract by removing excess sodium from the body. An extract of soursop has been shown to help heal gastric ulcers in lab animals. Like most fruits and vegetables, soursop is a good source of antioxidants, which might help the body repair cell damage and combat inflammation.
With such abundance of health benefits listed above, these fruit juices and mixtures are in high demands owing to the facts that the liquid form (a) is the easiest way to consume and it tastes delicious, (b) is easy to preserve and high in availability. Furthermore, consumer demands for unpasteurized fruit juices have increased because they have lower content of sodium, cholesterol and fat, and higher concentration of vitamin C, polyphenols, minerals, and antioxidants than fruits with preservatives. However, fruit juices are spoiled primarily to to proliferation of acid tolerant and osmophilic microflora. There is also risk of food borned microbial infections which is associated with the consumption of fruit juirces. If left outside of the refrigerator for 15 minutes, these fruit juices would have adverse effects on the stomach and intestines. If prepared in unhygienic conditions, these fruit juices may lead to diarrhea and other illnesses. Yeasts, decomposition bacteria, and pathogenic bacteria such as salmonella can contaminate amberella fruit juice during the peeling and extraction processes. In order to reduce the incidence of outbreaks, fruit juices are preserved by various techniques.
The traditional preservation of the fruit juice by boiling at high temperatures will cause it to lose a lot of nutrients, color, and it delicate fragrance. If fact, boiling the fruit juice creates sugar, which is different from the original fruit juice. Adding acidulant and preservatives to preserve the fruit juice from microorganism affects the juice color and taste, causing final consumers to turn it down.
Most artisan farmers peel the skin the fruits, remove their seeds, cut the fresh into pieces, crush them in a juicing screw press, and then sieve them to remove the pulps. Conventional juicing screw press is consisted of at least one screw presses that move the fruits from a low pressure region to a high pressure region, separating the juice and the pulps. For preservation, the extracted fruit juices are boiled in open pans at high temperatures between 89° C. to 92° C. until soluble solid contents near to 70 Brix. The concentration of soluble solids in the juice increases the temperature, exceeding 100° C. Just before of the syrup solidification, the temperature is ranging between 118° C. to 125° C., and the soluble solid content of syrup is higher than 88 Brix.
Thermal pasteurization is used commercially in fruit juice industries for the preservation of fruit juices but results in losses of essential nutrients and changes in physicochemical and organoleptic properties. Nonthermal pasteurization methods such as high dydrostatic pressure, pulsed electric field, and ultrasound and irrationtions have also been employed in fruit juices to overcome the negative effects of thermal pasteurization. However, some of these techniques are only in the research or pilot scale. Some of them have been commercialized but very expensive.
Another common method to preserve the liquid form fruit juice is a conventional vacuum freeze drying apparatus. In the traditional vacuum freeze drying method (lyophilization), temperature and vacuum are controlled to achieve sublimation and desorption of water vapors from the product. In addition to avoid changes in the dried product appearance and characteristics, drying by sublimation can yield a product that has a short reconstitution time with acceptable potency levels. However, the traditional vacuum freeze drying method usually reduce chemical stability of high-water content products such as fruits.
However, these well-known methods of extracting, sanitizing, and preserving fruit juices are inefficient that need improvements. First, the prior-art screw press juicing machines do not have high extraction efficiency due the design of the screw press. The extraction efficiency of the prior-art screw press juicing machines ranges between 34%-80%. In the U.S. Pat. No. 4,323,007 by Hunt (hereinafter referred to as the '007 patent), a screw 20 consists of a base 22 mounted to and concentric with drive shaft 26. The drive shaft 26 has a small diameter at its front end and a large diameter at its rear end with its surface forming a frusto-conical shape having a continuous slope. Spiral screw threads 24 are affixed to the surface of the body portion 22 and have a constant diameter with sufficient clearance to turn with the walls of the cage 40. The efficiency of the screw press of the '007 patent is 80%. Furthermore, the method and apparatus of the '007 patent create opportunities for microorganisms to contaminate the extracted juice.
Therefore, what is needed is a method and a system that can convert extracted fruit juice to concentrated powder which is chemically stable, has a long shelve life, short reconstitution time with excellent potency levels—the original fragrance, nutrients, vitamins, color are preserved.
What is needed is a system that includes an industrial screw press apparatus that has a high extraction efficiency and high output capacity.
What is needed is a system that are fully automatic, i.e., controlled and observed by a controller unit or a computer that can create optimal freeze drying conditions for fruits.
What is needed is system that can provide a high rate of cooling so that the microscopic structures of fruits are preserved.
Yet, what is needed is a system that can provide specific settings including eutectic temperatures (Teu), optimal temperatures (Topt), pressures, and cooling rates for fruits so that structural collapse can be avoided.
Finally, what is needed is a fruit juice composition powder that includes probiotics so that it is easy to digest after reconstitution by mixing with water.
The method and system disclosed in the present invention solve the above described problems.

Concentrated fruit juice powder and method for preparing the same using a non-linear screw press juicer and convection current freeze drying apparatus


A soccer training aid uses a conforming fabric upper attached to a soccer shoe with straps passing between the cleats. The upper provides a foundation for colored targets indicating proper kicking points for soccer.

The present invention is related to training aids for soccer, and specifically to a device to teach young soccer players the optimum contact areas on each foot for kicking a soccer ball.
Young children's first attempt in organized competitive sports is often on the soccer field. Aspiring soccer players are full of energy and enthusiasm, but often have difficulty in taking directional instructions (e.g., kick the ball with the instep of your right foot) and are easily discouraged when mistakes are made. Consequently, teaching the fundamental kicks used in the game of soccer is a difficult process for even the most experienced coaches.
There are four basic areas of the foot used to propel a soccer ball. They are the inside of the foot; inside of the instep; the instep; and the outside of the foot. Each kick is used for a different purpose, to accomplish different results throughout the game.
Teaching these fundamentals to the novice player should be the main focus for coaches throughout the player's first two to three seasons of play. However, many coaches volunteer with little or no knowledge of these basic kicks or the developmental stage of these young players. Consequently, these players receive little accurate feedback as to the proper execution of these fundamental skills.
Attempts have been made to attach targets to a player's shoes to indicate the correct points of contact between the foot and the soccer ball for various kicks. The difficulty of affixing such a target to a soccer shoe, in a way that will resist the force of a soccer kick, has limited these targets to locations on the instep, that is the top of the foot where the laces of the shoes are located. This single location has limited the usefulness of such attachable targets.
Alternatively, specialized soccer training shoes have been created with colored patches. These shoes provide a greater variety of target areas but are an impractical expense in most junior leagues.


An operating element arrangement controls the longitudinal and transverse movements of a motor vehicle, with a foot-actuatable regulating part for controlling braking operations. The operating element arrangement contains a regulating part for controlling the transverse movement of the vehicle, which is arranged so as to be manually actuatable in the transverse direction of the vehicle and into which a finger-actuatable regulating part for controlling acceleration operations is integrated. A steering wheel and accelerator pedal can be eliminated, and a distinct spatial and operationally functional separation of the activation of braking operations, on one hand, and of acceleration operations, on the other hand are provided.

This application claims the priority of 196 25 501.5, the disclosure of which is expressly incorporated by reference herein.
This application is related to application Ser. No. 08/881,384 filed on Jun. 24, 1997 in the name of Michael BOEHRINGER et al. for OPERATING ELEMENT ARRANGEMENT FOR CONTROLLING MOTOR VEHICLE LONGITUDINAL AND TRANSVERSE MOVEMENTS; application Ser. No. 08/877,404 filed on Jun. 17, 1997 in the name of Michael BOEHRINGER et al. for OPERATING ELEMENT ARRANGEMENT FOR CONTROLLING MOTOR VEHICLE LONGITUDINAL AND TRANSVERSE MOVEMENTS; application Ser. No.08/883,502 filed on Jun. 26, 1997 in the name of Lutz ECKSTEIN et al. for OPERATING ELEMENT ARRANGEMENT FOR CONTROLLING MOTOR VEHICLE LONGITUDINAL AND TRANSVERSE MOVEMENTS; application Ser. No. 08/882,930 filed on Jun. 26, 1997 in the name of Lutz ECKSTEIN et al. for OPERATING ELEMENT ARRANGEMENT FOR CONTROLLING MOTOR VEHICLE LONGITUDINAL AND TRANSVERSE MOVEMENTS; application Ser. No. 08/883,480 filed on Jun. 26, 1997 in the name of Michael BOEHRINGER et al. for OPERATING ELEMENT ARRANGEMENT FOR CONTROLLING MOTOR VEHICLE LONGITUDINAL AND TRANSVERSE MOVEMENTS.
The present invention relates to an operating element arrangement for controlling the longitudinal and transverse movements of a motor vehicle, with a foot-actuatable regulating part for activating braking operations.
In conventional operating arrangements as are used, for example, in automobiles, a foot-actuatable regulating part is formed by a brake pedal. A foot-actuatable accelerator or driving pedal is provided for activating acceleration operations, and the control of transverse movement, i.e vehicle steering, is carried out via a steering wheel. The paper by P. Branneby et al., Improved Active and Passive Safety by Using Active Lateral Dynamic Control and an Unconventional Steering Unit", 13th International Technical Conference on Experimental Safety Vehicles, 4th to 7th November 1991, Proceedings Vol. 1, page 224, proposes, as an alternative to the conventional steering wheel, an operating lever which is arranged, for example, on the center tunnel of the vehicle.
Furthermore, a common operating element for controlling the longitudinal and transverse dynamics of a motor vehicle is known, preferably in which the longitudinal dynamics are controlled by actuating the operating element in the longitudinal direction of the vehicle and the transverse dynamics are controlled by actuating the operating element in the transverse direction, in particular as a rotational movement corresponding to the conventional steering wheel.
An operating element is disclosed in U.S. Pat. No. 3,022,850 in the form of a control stick which is mounted on a frame so as to be pivotable about a horizontal transverse axis, the frame, in turn, being rotatable about a horizontal longitudinal axis. A further operating element of this type, which is alluded to in a paper by H. Bubb, Arbeitsplatz Fahrer--Eine ergonomische Studie [Driver's area--An Ergonomic Study], Automobil-Industrie [Automobile Industry] 3/85, page 265, contains two mechanically interconnected plate-like handles which are located closely next to one another and which are attached to the end of a bar which is guided movably on the vehicle center console. The longitudinal dynamics of the vehicle are controlled by displacing the bar in the longitudinal direction of the vehicle, and the transverse dynamics are influenced by rotating the two plate-like handles in the transverse plane of the vehicle.
German Patent Application 195 48 717.6 discloses an operating element arrangement for controlling the longitudinal and transverse movements of a motor vehicle. The arrangement comprises two operating elements which can be actuated independently of one another and each of which is intended for controlling the longitudinal and transverse movements and is preferably designed as a manually actuatable control stick. Electronic coupling of the two operating elements prevents command collisions, e.g. caused by the additive superposition of the control command signals, due to the manual passive switching of one operating element in each case or due to the assignment of different priorities for the two operating elements.
DE 28 41 786 A1 discloses an operating element arrangement for controlling the longitudinal and transverse movements of a motor vehicle. The arrangement contains, for controlling longitudinal acceleration operations, a conventional, foot-actuatable accelerator pedal and a manually actuatable actuating wheel which is coupled mechanically to the latter and which is arranged on a conventional steering wheel, serving for the control of transverse movement, so as to be rotatable together with the said steering wheel and displaceable axially relative thereto. This arrangement also enables the disabled to drive motor vehicles having a conventional pedal assembly by making the pedal controls hand actuatable.
DE 43 01 292 A1 describes an arrangement in which, in addition to a conventional steering wheel serving for the control of transverse movement, a manually actuatable brake knob coupled to a conventional brake pedal and intended for activating the vehicle brake. Furthermore, the arrangement contains a device for regulating the longitudinal speed, and the desired speed value can be decremented merely by touching the brake knob and can be incremented by actuating push buttons provided in the steering wheel. In a standard operating mode without speed regulation, acceleration operations are controlled via a conventional, foot-actuatable accelerator pedal.
U.S. Pat. No. 5,309,361 discloses a foot-actuatable operating element arrangement for controlling the longitudinal movement of a vehicle, in which the brake pedal and accelerator pedal are hemispherical force sensor elements which give way to an external pressure actuation force.
An object of the present invention is to provide an operating element arrangement for controlling the longitudinal and transverse movements of a motor vehicle with a high level of driving and operating comfort.
The present invention achieves this object by providing an operating element arrangement having a foot-actuatable regulator configured and arranged to control braking operations, and a manually actuatably, steering control stick configured to control transverse movement of the motor vehicle and arranged to be subjected to actuating forces acting in a transverse direction of the motor vehicle, wherein a finger-actuatable regulating part configured to control acceleration operations of the motor vehicle is integrated into the steering control stick.
In the arrangement of the present invention, a regulating part which is manually actuatable in the transverse direction of the vehicle and is in the form of a steering control stick controls the transverse movement of the vehicle, i.e. vehicle steering. Integrated into this manually actuatable regulating part is a finger-actuatable regulating part which controls acceleration operations and which consequently performs the function of a conventional, foot-actuatable accelerator pedal.
In comparison with conventional arrangements having a steering wheel and a brake and accelerator pedal assembly, numerous advantages are afforded. Thus, for example, active safety with regard to the longitudinal dynamics is improved. That is, for alternate acceleration and braking, the foot no longer has to be changed over between the accelerator pedal and brake pedal. Instead, the activation of acceleration operations is separated from the activation of braking operations spatially and, as regards the operating mode, distinctly.
Moreover, braking operations in accordance with the present invention can be initiated substantially more quickly. Furthermore, dispensing with the accelerator pedal does away with the risk of actuating the wrong pedal. Further, operating safety and operating comfort are increased by the possibility of driving the vehicle more intuitively and with a more comfortable body posture. By dispensing with the accelerator pedal and with the conventional steering wheel, free spaces occur in the driver's seat region and may be utilized for the more advantageous placing of other instruments in the dashboard region.
In addition, with a laterally arranged steering control stick as contemplated by the present invention, the driver's arms need not be held stretched so far forwards as in the case of the conventional steering wheel. Furthermore, dispensing with the accelerator pedal and with the steering wheel improves passive safety; i.e. in the event of a rear-end collision, the risks of injury associated with these elements does not arise. Furthermore, the omission of the conventional steering wheel and accelerator pedal may be utilized for the purpose of shortening the vehicle, while, at the same time, ensuring the same amount of available space, and of providing more convenient possibilities for getting into the vehicle.
In comparison with known arrangements having an operating element which controls both longitudinal and transverse dynamics and, for this purpose, can be subjected to an associated actuating force in the longitudinal and transverse directions, an advantage of the present operating element arrangement is that only the transverse movement of the vehicle is influenced by the force exerted on the manually actuatable regulating part. There is no possibility of an actuating force component in the longitudinal direction of the vehicle inadvertently having an undesired influence on the longitudinal dynamics of the vehicle at the same time. On the contrary, the vehicle driver's hand actuating the regulating part may be supported on this regulating part in the longitudinal direction of the vehicle.
In an embodiment of the operating element arrangement according to the present invention, the steering control stick can be arranged to the side of a driver's seat. If required, a steering control stick may be provided on both sides of the driver's seat, in which case the two sticks can be operated in parallel, suitable measures ensuring that no command collisions occur.
The present invention can incorporate the finger-actuatable regulating part into the manually actuated regulating part.
An operating element arrangement according to the present invention can contain, as a foot-actuatable regulating part for the control of braking operations, a large-area force sensor element which is arranged in the driver's seat floor region, i.e. approximately where the brake pedal is conventionally located. The large-area force sensor element, instead of a pedal, improves passive safety, because, not only the accelerator pedal, but also the brake pedal, and consequently the risks of injury associated with this pedal assembly, are absent.

Operating element arrangement for controlling motor vehicle longitudinal and transverse movements


Provided are an efficient method for producing 3,4-dihydroisoquinoline derivatives and useful production intermediates thereof. Provided is a method for producing 3,4-dihydroisoquinoline derivatives represented by general formula (1), comprising converting a compound represented by general formula (3) in the presence of acid after reacting with an aniline derivative, or converting a compound represented by general formula (3) by reacting with an aniline derivative in the presence of an acid.

Numerous chemicals have been proposed for the purpose of controlling diseases in agricultural and horticultural crops. For example, a 3,4-dihydroisoquinoline derivative represented by general formula (1):
wherein R1 and R2 independently represent an optionally substituted alkyl group having 1 to 6 carbon atoms or R1 and R2 together with the carbon atom to which they are bound form an optionally substituted cycloalkyl group having 3 to 10 carbon atoms, X represents a halogen atom, optionally substituted alkyl group having 1 to 6 carbon atoms or optionally substituted alkoxy group having 1 to 6 carbon atoms, n represents an integer of 0 to 4, Y represents a halogen atom, optionally substituted alkyl group having 1 to 6 carbon atoms or optionally substituted alkoxy group having 1 to 6 carbon atoms, and m represents an integer of 0 to 4, is disclosed in Patent Document 1 as being useful as an agricultural and horticultural microbicide. Moreover, a group of compounds derived from a compound represented by general formula (1) are also effective as agricultural and horticultural microbicides, and these compounds can also be intermediates for the production of agricultural and horticultural microbicides (Patent Document Nos. 1 and 2). Consequently, being able to produce these compounds both simply and efficiently is an extremely important issue.
According to Patent Document 1, a compound represented by general formula (1) is disclosed as being able to be prepared by using a 3-cyanoquinoline derivative as a starting material and reacting with a phenethyl alcohol derivative or styrene derivative, thus demonstrating that a 3-cyanoquinoline derivative is an important raw material.
An examination of the prior art relating to 3-cyanoquinoline reveals that it is produced by methods such as: (I) a method in which 3-bromoquinoline and copper cyanide are reacted at 250° C. (Non-Patent Document 1), (II) a method in which 2-dimethoxymethylacrylonitrile and aniline are reacted followed by converting with aluminum chloride (Non-Patent Document 2), (III) a method in which 4-nitroquinoline-1-oxide and potassium cyanide are reacted followed by chlorinating with phosphorous oxychloride and further subjecting to catalytic hydrogenation using palladium as catalyst (Non-Patent Document 3) for conversion, (IV) a method in which 3-bromoquinoline, sodium cyanide, potassium iodide, copper iodide and dimethyl ethylenediamine are reacted for 24 hours in toluene for conversion (Patent Document 3), and (V) a method in which aniline and a sodium salt of 3,3-dimethoxy-2-formyl propionitrile are reacted in the presence of hydrochloric acid followed by converting to a substituted cyanoquinoline with p-toluenesulfonic acid (Non-Patent Document 4).
However, these methods have the problems indicated below. In the method of (I), in addition to requiring an extremely high reaction temperature of 250° C., copper cyanide is used, which is highly toxic and causes problems on disposal. In the method of (II), the total yield is only about 4%, thus indicating poor productivity. In the method of (III), in addition to using highly toxic potassium cyanide, catalytic hydrogenation using an expensive palladium catalyst only demonstrates a yield of about 56%. In the method of (IV), in addition to using transition metals that present problems on disposal and highly toxic sodium cyanide, the reaction time is long resulting in it being not an efficient method. In the method of (V), although the method per se is superior, the substituents on aniline are limited to strong electron donating groups such as a methoxy group. On the other hand, the reaction does not proceed not only in the case of aniline substituted with a fluorine atom or methyl group, but also in the case of unsubstituted aniline, thereby indicating that this method lacks versatility.
As can be understood from the above, since conventional production methods using 3-cyanoquinoline derivatives as starting materials have problems with respect to productivity of the 3-cyanoquinoline per se as well as only allowing the acquisition of 3-cyanoquinoline having a limited range of substituents, there has been a fervent desire for a method for efficiently producing 3,4-dihydroisoquinoline derivatives as an alternative to these methods.

Method for producing 3,4-dihydroisoquinoline derivatives and production intermediates of same


A cashless play system for arcade games on passenger ships utilizes a key card reader to read patron identity information. The key card reader sends the patron identity information to a shipboard game play server and receives game play authorization information based on the patron identity information and patron data stored in a shipboard patron database. The key card reader activates the arcade game based on the game play authorization information and causes game play data to be stored in a game play database. Further, the game play server uploads game play data to a remote server, at a geographic location other than the geographic location of the passenger ship, and downloads game play server updates.

Arcade game operators prefer to install arcade games, such as video games, pinball games, redemption games, claw cranes, etc., in locations where people may be localized for long periods of time, such as hotels, restaurants, shopping centers, and other public places. In particular, cruise ships are suitable locations for arcade games. Often passengers on cruise ships are domicile on the cruise ship for days at a time giving the passengers frequent opportunities to utilize arcade games.
However, maintaining a network of arcade games on cruise ships presents various difficulties to the operator of the arcade games. The operator must process payments for games, repair broken games, and change game pricing while the cruise ship is in port, and often cruise ships are only in port for a matter of hours. The operator may not be able to accommodate such a tight time schedule, and the operator has no opportunity to view game play statistics, transaction information, and game errors while the ship is at sea. Moreover, passengers on cruise ships often use a room or account key card to make shipboard purchases. As such, passenger may lack the cash needed to play arcade games or it is not immediately convenient to activate a game.


A fuel-supply manifold assembly has a thin-wall tube extending along a tube axis and formed with a plurality of radially throughgoing ports and respective saddle fittings each formed with a face complementary to and fitting with an outer surface of the tube at a respective one of the ports and with a throughgoing passage having an inner end aligned with the respective port. Respective tubular alignment nipples each have a throughgoing passage and each further have an inner end seated in a respective one of the ports and an outer end seated in the inner end of the respective fitting.

A prior-art gasoline engine internal-combustion has as shown in FIG. 1 a manifold tube 2 that connects the high-pressure fuel pump to the fuel injectors of the engine's cylinders. This manifold tube 2 is pressurized normally at about 200 bar and the pressure in it can peak at 450 bar, reaching a staggering 1600 bar for some diesel systems. The tube 2 is typically made of stainless steel so that it can resist both this enormous pressure and the chemical attack of the fuel. As a result of the cost of the steel, its weight, and the difficulty working it, it is invariably made of relatively thin stock so that it is impossible, for instance, to thread ports 5 in it from which the fuel exits to the injectors.
Hence the tube 2 is provided as described in German 100 20 605 and 197 44 762 with saddle fittings 3 that are secured to the outside surface of the tube 2 at the ports 5. Each fitting 3 is formed with a throughgoing passage 4 of a flow cross section that is normally somewhat greater than that of the respective port 5, both normally being circular in section, so that if the passage 4 does not extend perfectly radially of the tube 2 or is not perfectly centered on the respective port 5 the fuel can still pass.
Making up such a manifold assembly 1 is fairly difficult. Once the manifold tube 2 is drilled to have the necessary ports 5, the saddle fittings 3 must be positioned to align their passages 4 perfectly with the respective ports 5, then they are soldered or welded in place at the joint 6. Unfortunately, each saddle fitting 3 covers its port 5 and, since the passage 4 in the fitting 3 is often oriented nonradially of the tube 2, it is impossible to verify the position. Inserting an alignment pin through the fitting passage 4 into the port 5 to ensure proper alignment is moderately effective although difficult to do in a mass-production operation. Typically the fitting 3 is spot-welded to the tube 2 when aligned with a pin, then the entire manifold assembly 1 is welded in one operation, in which case the previously made spot weld blocks the ability of the solder wash to enter the joints 6 between the fittings 3 and the tube 2.
Any misalignment, even a very minor one, creates a restriction that produces turbulence in the passing fluid. When the fitting passage 4 is of greater diameter than the port 5, which is common, the port edges create turbulence even with perfect alignment. What is more, the solder holding the fitting 3 to the tube 2 is exposed to the fuel passing through the assembly and can be attacked by it, weakening the joint and possibly creating a dangerous leak.


An exposure apparatus includes a projection optical system for projecting exposure light, with which a reticle formed with a pattern is irradiated, onto a wafer, a stage for holding and aligning the wafer or reticle, an alignment optical system for outputting alignment light, a reflection mirror provided on the stage, and a plurality of interferometers for measuring the position of the stage by irradiating the reflection mirror with measurement light. The interferometer to be used to measure the position of the stage in a predetermined direction is switched to another in accordance with whether the stage is aligned to the projection optical system or to the alignment optical system.

The present invention relates to a stage apparatus which is used in a semiconductor exposure apparatus, inspection apparatus, or the like, and aligns an exposure master disk, an object to be exposed, or an object to be inspected to a predetermined position, and its control method.
In general, as exposure apparatuses used in the manufacture of semiconductor elements, an apparatus called a stepper, and an apparatus called a scanner are known. The stepper projects a pattern image formed on a reticle on a semiconductor wafer on a stage apparatus in a reduced scale via a projection lens while stepping the wafer beneath the projection lens, thus sequentially forming the pattern image by exposure on a plurality of portions on the single wafer. The scanner moves a semiconductor wafer on a wafer stage and a reticle on a reticle stage relative to a projection lens (scan movement), and projects a reticle pattern on the wafer by irradiating it with slit-patterned exposure light during the scan movement. The stepper and scanner are considered as mainstreams of the exposure apparatus in terms of their resolution and superposing precision.
FIG. 21 is a schematic top view of a wafer stage used in such an exposure apparatus.
A wafer 102 to be exposed is mounted on a wafer stage 101 via a wafer chuck (not shown). With reference to an exposure optical system, the position of an exposure optical axis 103 is fixed in FIG. 21. Hence, the wafer stage 101 must move in the X- and Y-directions with respect to the exposure optical axis 103 to expose the entire surface of the wafer. The wafer 102 must also move in the Z- and tilt directions to adjust the imaging focal point, but a detailed description thereof will be omitted herein. The position measurement of the wafer stage 101 in the X- and Y-directions uses a high-resolution laser interferometer to realize high-precision alignment. In order to use the laser interferometer, a reflection mirror 107 for reflecting a laser beam must be provided on the wafer stage 101. However, since this reflection mirror 107 must reflect the laser beam to cover the entire moving range of the wafer stage 101, it requires a length equal to or larger than the moving distance of the wafer stage 101. That is, if Ly represents the stage moving distance in the Y-direction, the length Lx of a reflection mirror for X-measurement requires Ly or more (=Ly+xcex1).
The moving range of the wafer stage 101 need only be slightly larger than the wafer diameter if exposure alone is done. However, in practice, the wafer stage 101 moves not only in an exposure operation but also in other operations.
In order to expose the wafer 102, alignment must be done with high precision with respect to the imaging point. Various alignment methods are available, and a method that irradiates an alignment mark, which has been exposed and transferred onto a wafer in advance, with alignment light to obtain any alignment error amount from light reflected by the mark is prevalently used. In this alignment method, the alignment optical axis center does not often match the exposure optical axis center.
FIG. 22 shows a general wafer stage when an alignment optical axis center 104 does not match the exposure optical axis center 103. Referring to FIG. 22, the alignment optical axis center 104 strikes a wafer at a position a given distance L2 from the exposure optical axis center 103. The wafer stage 101 must move the wafer 102 in the X- and Y-directions to expose the entire surface of the wafer, and must also move it in the X- and Y-directions to irradiate the entire surface of the wafer with the alignment light 104.
For this purpose, the movable range of the wafer stage 101 must be broadened by the displacement between the alignment optical axis 104 and exposure optical axis 103. Consequently, the length of the reflection mirror 107 must be increased by the broadened size of the moving range of the wafer stage.
Referring to FIG. 22, a length Lx2 of the reflection mirror in the X-direction must be increased by a displacement L2 between the alignment optical axis 104 and exposure optical axis 103.
More specifically, in FIG. 22, assume that an X-interferometer optical axis 105 passes through the exposure optical axis center 103, and a Y-interferometer optical axis 106 passes through the exposure optical axis center 103 and alignment optical axis center 104. Let Ly be the stage moving distance in the Y-direction (the distance between the position (solid line) where the wafer stage 101 has moved a maximum distance in a +Y-direction, and the position (broken line) where the stage 101 has moved a maximum distance in a xe2x88x92Y-direction), and L2 be the distance between the exposure optical axis center 103 and alignment optical axis 104. Then, the minimum required length Ly2 of the reflection mirror 107 is given by Ly2=Ly+L2.
Especially, in recent years, the wafer diameter becomes as large as 300 mm to improve productivity. In order to expose the entire surface of the wafer, the wafer stage must have a moving range at least equal to or larger than the wafer diameter. As the wafer alignment position may be different from the exposure position, and wafers must be exchanged, the moving range must be further broadened. Inevitably, the length of the reflection mirror increases.
However, a reflection mirror 107 having such a large length is not preferable since (1) it is hard to prepare a long reflection mirror having a high-precision mirror surface, (2) high cost is required to prepare the mirror surface of such a long reflection mirror, (3) the weight of the reflection mirror itself increases and results in an increase in total weight of the stage, (4) heat produced by a stage driving device increases due to an increase in stage weight, and (5) the characteristics of a control system deteriorate due to a decrease in natural frequency of a mechanical system of the stage.
In order to solve this problem, an arrangement described in Japanese Patent Laid-Open No. 7-253304 has been proposed. This apparatus comprises a laser interferometer distance measuring device, movable mirror, X-Y moving stage, and arithmetic device. The movable mirror has a length shorter than the stage moving distance in the Y-direction, and a plurality of X-interferometers are provided. The spacing between neighboring X-interferometers is shorter than the length of the movable mirror, and the movable mirror is irradiated with measurement light of one of the X-interferometers independently of the current position of the stage and is sometimes irradiated with measurement light from two X-interferometers. Which of the X-interferometers is ready to measure is determined by the arithmetic device based on the value of a Y-interferometer, and a measurement result in the X-direction is obtained. Upon moving the stage in the Y-direction, a new X-interferometer which becomes ready to measure undergoes recovery operation at a predetermined position using the value of the interferometer that has been used in measurement so far. By passing the values in turn, movement over a broad range is measured using the short movable mirror.
According to the arrangement described in Japanese Patent Laid-Open No. 7-253304, size and weight reductions of a position measurement mechanism (reflection mirror) to be mounted on a stage can be achieved. However, since the plurality of interferometers are selectively used, the process throughput lowers, and the measurement precision is not sufficiently high. According to the findings of the present inventors, such shortcomings are caused for the following reasons.
The recovery operation of each interferometer requires a certain time, and cannot fall within one sample time of a stage control system. Hence, even by the recovery operations of the interferometers like in the conventional system, measurement values cannot be continuously passed to a control system.
The X-Y stage must be aligned with high precision, and alignment is done by a control system that uses feedback of the measurement value of the stage position. The stage control system comprises a digital control system based on high-frequency sampling, and uses high-gain feedback. Observation noise of a position measurement system is disturbance to the control system, and if its influence is serious, the closed loop characteristics of the control system cannot be improved.
Oscillation noise inevitably appears in the measurement value of the laser interferometer. Such noise is produced due to electrical noise in the measurement system and mechanical vibration of the reflection mirror and laser interferometers themselves. Hence, upon passing the interferometer value, a value on which this noise is superposed is passed. For example, when the stage is aligned to stop near the switching position of the laser interferometers, chattering including a large number of times of switching of laser interferometers and value passing may occur due to slight vibration of the stage and noise of the switching position measurement system. When the value on which noise is superposed is passed a large number of times, errors accumulate, and the measurement error between the true stage position and the measurement value may become large.
It is, therefore, an object of the present invention to attain size and weight reductions of a position measurement mechanism (e.g., a reflection mirror and linear scale) mounted on a stage even when the moving range of the stage is broadened.
It is another object of the present invention to minimize deterioration of the position measurement precision resulting from switching of position measurement means by switching the position measurement means in units of predetermined work regions (e.g., exposure process regions, alignment regions) so as to reduce the number of times of switching of the position measurement means.
It is still another object of the present invention to provide an arrangement which can attain size and weight reductions of a position measurement mechanism mounted on the stage and can measure the stage position with high precision, even when the moving range of the stage is broadened.
It is still another object of the present invention to prevent the position measurement means from being switched frequently due to vibration of the stage even when the stage is stopped near the switching position of the position measurement means.
It is still another object of the present invention to obviate the need for increasing the length of an object required in position measurement such as a reflection mirror, linear scale, and the like to be mounted on the stage even when the alignment optical axis and exposure optical axis are separated from each other in an exposure apparatus and a device manufacturing method using that apparatus, and to improve the process throughput and position measurement precision.
Other features and advantages of the present invention will be apparent from the following description taken in conjunction with the accompanying drawings, in which like reference characters designate the same or similar parts throughout the figures thereof.

Stage control apparatus and exposure apparatus


A wireless apparatus has a main housing, a movable housing relatively extended to the main housing. The main housing contains a first PCB with a first layer being fully laid metal material. The movable housing contains a second PCB with a second layer being fully laid metal material. An insulation route is laid on the second layer and led to the border of the second layer. A connection component electronically connects the first layer and the second layer. When the wireless apparatus is operated at wireless communication, the cooperation of the first layer, the second layer, the insulation route and the connection component adjusts the electrical characteristic of the first and second PCBs for eliminating a parasitic effect being caused of movement of the first and second PCBs and increasing gain of the antenna of the wireless apparatus.

1. Field of the Invention
The invention relates to a wireless apparatus for increasing antenna gain, and particularly to a wireless apparatus capable of eliminating parasitic effect and increasing antenna gain.
2. The Related Art
According to the advancement of wireless communication technology and wireless communication service, a wireless communication apparatus is necessary for life, and particularly a mobile phone. The mobile phone with powerful function and small volume is getting popular nowadays. Therefore, the downsizing issue is one of designed targets for the mobile phone.
The mobile phone for the mentioned downsizing issue contains problems both at the closed position and the opened position as well. The mobile phone is operated at wireless communication in the opened position, else in the closed position. When the mobile phone is in the opened position, the movable housing of the mobile phone relatively moves to the main housing of the mobile phone, for example the movable housing rotates on the main housing, the movable housing slides on the main housing, etc.
According to the movement of the main housing and the movable housing, a main printed circuit board received in the main housing and a sub printed circuit board received in the movable housing relatively move to each other. The main printed circuit board electronically connects the sub printed circuit board through a connection component.
According to the movement of the main printed circuit board of the main housing and the sub printed circuit board of the movable housing, the mobile phone is caused a parasitic effect. The parasitic effect influences gain of the antenna of the mobile phone. While considering the parasitic effect, the antenna or layout of the main printed circuit board and the sub printed circuit board are re-designed. Therefore, time cost for re-designed of the antenna, the main printed circuit and the sub printed circuit board is raised.

Wireless apparatus for increasing antenna gain


In a dielectric resonator device, the outer shape of a support base is larger than the bottom surface of a dielectric core which is in contact with the support base, and the support base is fixed on the inner bottom surface of the cavity with support columns at the periphery of the support base. With this configuration, an air space can be provided between the inner bottom surface of the cavity and the support base. Accordingly, the resonant frequency of the TMz mode in which the electric field vector directs perpendicularly to the surface of the support base is increased so that it is considerably away from the resonant frequency of the TE01δ multiple mode.

1. Field of the Invention
The present invention relates to a dielectric resonator device operating in a multiple mode, and also to a dielectric filter, a composite dielectric filter, and a communication apparatus provided with the above type of dielectric resonator device.
2. Description of the Related Art
Japanese Unexamined Patent Application Publication No. 11-145704 discloses a multiple-mode dielectric resonator device utilizing a plurality of resonant modes in which a dielectric core is disposed in a cavity.
In the dielectric resonator device of the above-described publication, a dielectric core generally formed in a rectangular parallelepiped is disposed at the center of a cavity generally formed in a rectangular parallelepiped. Support bases having a low dielectric constant are attached by glass glazing to the dielectric core, which is integrally formed with the cavity, provided with provisional support members, and are then fired. Subsequently, the provisional support members are removed. The structure in which a dielectric core is supported at the center of the cavity by disposing a support base under the dielectric core is also disclosed in this publication.
However, the structure in which the dielectric core is supported in the cavity by providing the provisional support members presents the following problems:
(1) complexity of the manufacturing process;
(2) necessity to increase the dimensional precision of the dielectric core, the cavity, and the support bases; and
(3) complexity of molding dies for the dielectric core and the cavity.
Because of the above-described problems, the cost of the resulting dielectric resonator device becomes high.
In the structure in which the dielectric core is disposed in the cavity by disposing the support base therebetween, the effective dielectric constant in the direction in which an electric field vertically passes through the contact face between the support base and the dielectric core is increased by the height of the support base, which serves as a dielectric member, and accordingly, the resonant frequency of the resonant mode (TM mode) in the above-described direction is decreased. If the TM mode is an unwanted resonant mode, this adversely influences the characteristics, for example, filter attenuation characteristics, obtained by the other resonant modes. Even if the TM mode is utilized, the dielectric resonator device must be designed by taking into consideration the decrease in the resonant frequency due to the presence of the support base, thereby decreasing designing flexibility.

Dielectric resonator device, dielectric filter, composite dielectric filter, and communication apparatus


The invention relates to stable compositions of proteins and related methods wherein a protein capable of transitioning into the molten globular state is contacted with a negatively charged lipid vesicle, thereby stabilizing the protein against thermally-induced aggregation, denaturation, and loss of activity. The protein:phospholipid complex directly stabilizes the secondary and tertiary structure of the protein, and the compositions are useful in high temperature formulations and in novel delivery vehicles.

The present invention relates to protein:phospholipid structures which are useful for stabilizing the secondary and tertiary structure of proteins capable of transitioning into the molten globular state. More particularly, this invention relates to G-CSF:phospholipid and MGDF:phospholipid compositions having increased stability, exhibiting increased shelf life, and capable of use in high temperature formulations and as novel delivery vehicles.
Several proteins have been shown to transition into a molten globular state (MGS). Van der Goot, F. G., Nature 354, 408-410 (1991). Proteins in the molten globular state exhibit secondary structure which is comparable to the native protein yet they lack rigid tertiary structure. Pitsyn et al., FEBS Letters 262:1, 20-24 (1990). In some cases, transition into this state is accompanied by exposure of previously hidden hydrophobic regions of the protein. By exposing critical hydrophobic residues, the MGS may be an intermediate in the aggregation and precipitation of proteins. The MGS conformation can be detected by comparing the circular dichroism in the far UV region with the spectra of aromatic side chains (near UV circular dichroism and fluorescence). The molten globular state exhibits aromatic group spectral changes in the absence of far UV circular dichroism changes, Bychkova et al., FEBS Letters 238: 231-234 (1988),and may be involved in membrane penetration by some proteins Bychkova et al., FEBS Letters 238: 231-234 (1988); Van der Goot, F. G., Nature 354, 408-410 (1991).
Granulocyte colony stimulating factor (G-CSF) is one protein known to transition into the MGS prior to aggregation. Human recombinant G-CSF selectively stimulates neutrophils, a type of white blood cell used for fighting infection. Currently, Filgrastim, a recombinant C-CSF, is available for therapeutic use. The structure of G-CSF under various conditions has been extensively studied; Lu et al., J. Biol. Chem. Vol. 267, 8770-8777 (1992). Because of its hydrophobic characteristics, G-CSF is difficult to formulate for extended shelf life. Formulations of certain hydrophobic proteins lose activity due to formation of dimer and higher order aggregates (macro range) during long-term storage. Other chemical changes, such as deamidation and oxidation may also occur upon storage. In addition, the G-CSF formulator must protect against denaturation and, in particular, look to maintain the stability of the secondary and tertiary structure of the protein.
Human GM-CSF is a 22-kDa glycoprotein required continuously for the in vitro proliferation of macrophage and granulocytic progenitor cells. It also controls the irreversible commitment of these progenitors to form granulocytes and macrophages. Other biological activities may include regulation of the functional activity of mature cell types; Gough et al., Nature, 309, 763-767 (1984), and increasing chemotaxis towards recognized chemoattractants; Williams et al., Hematology, 4th ed. (1990). GM-CSF also stimulates the production of monocytes, and thus may be useful in the treatment of monocytic disorders, such as monocytopenia.
Human GM-CSF can be obtained and purified from a number of sources. Procedures for the production of recombinant human GM-CSF have been previously described by Burgess et al., Blood, 69:1, 43-51 (1987). U.S. Pat. No. 5,047,504 (Boone), incorporated herein by reference, has enabled the production of commercial scale quantities of GM-CSF in non-glycosylated form as a product of procaryotic host cell expression.
MGDF, or megakaryocyte growth and differentiation factor, is a recently cloned cytokine that appears to be the major regulator of circulating platelet levels. See Bartley, T. D. et al., Cell 77:1117-1124 (1994); Lok, S. et al., Nature 369:565-568 (1994); de Sauvage, F. J. et al., Nature 369:533-538 (1994); Miyazake, H. et al., Exp. Hematol. 22:838 (1994); and Kuter, D. J. et al., PNAS USA, 91:11104-11108 (1994). MGDF is also referred to as thrombopoietin (TPO), mpl-ligand, and megapoietin. Mature human MGDF is a protein having 332 amino acids in total. The sequence of this protein and the corresponding cDNA are shown in FIG. 29 herein.
Recombinant MGDF produced in both Chinese Hamster Ovary (CHO) and E. coli cells has been demonstrated to have a biological activity of specifically stimulating or increasing megakaryocytes and/or platelets in vivo in mice, rats and monkeys. See e.g., Hunt, P. et al., Blood 84(10):390A (1994). Human MGDF molecules that have been truncated so that they extend at least 151 amino acids, starting from amino acid position 1 in FIG. 29, retain biological activity in vivo. It is also possible to remove up to the first six amino acids at the N-terminus of the human sequence MGDF protein and retain biological activity. Therefore, it appears that biological activity is retained within amino acids 7 to 151 (inclusive) of the mature amino acid sequence of human MGDF shown in FIG. 29.
Naturally occurring MGDF is a glycosylated molecule. The glycosylation pattern of natural MGDF is related to two key domains that have been found in MGDF. The sequence of the first approximately 151 amino acids of human MGDF, corresponding to an active portion of the molecule, bears notable homology to erythropoietin (EPO), a cytokine capable of stimulating production of erythrocytes, and is referred to as the "EPO-like" domain of human MGDF. The remaining amino acids of the mature protein make up a so-called "N-linked carbohydrate" domain, since they include most if not all of the sites for N-linked glycosylation. In human MGDF, there are six N-linked glycosylation sites all contained in the N-linked glycosylation domain. Both domains contain O-linked glycosylation sites. There are an estimated 12-14 O-linked glycosylation chains in the molecule. Experimental evidence with human MGDF DNA expressed recombinantly in CHO cells reveals that in the EPO-like domain at least two O-linked sites are glycosylated, at positions 1 (Ser) and 37 (Thr).
While proteins such as G-CSF and MGDF may be stabilized under certain defined conditions, there still exists a need to extend the shelf life of these and other proteins by stabilizing the secondary and tertiary structure of the proteins. One way which has been tried in the past to work with such proteins is the use of liposomes. Liposomes are completely closed lipid bilayer membranes formed by water-insoluble polar lipids, particularly phospholipids. Liposome vesicles may have a single membrane bilayer (unilamellar) or may have multiple membrane bilayers (multilamellar). The bilayer is composed of two lipid monolayers having a hydrophilic (polar) "head" region and a hydrophobic (nonpolar) "tail" region wherein the hydrophobic tails orient toward the center of the bilayer, whereas the hydrophilic heads orient toward the aqueous phase. The stability, rigidity, and permeability of liposomes can be altered by changes in the phospholipid composition, by changes in temperature, by inclusion of a sterol or by incorporation of a charged amphiphile. The basic structure of liposomes may be made by a variety of techniques known in the art.
In the process of their formation liposomes can entrap water solutes in the aqueous channels and release them at variable rates. Upon the discovery that liposomes can introduce enzymes into cells and alter their metabolism (Gregoriadis, New Engl. J. Med. 295, 704-710, 765-770 (1976)), liposomes were heralded as the answer to the quest for targeted drug delivery. As a result, there is a great deal of developmental research in the pharmaceutical industry involving use of liposomes as slow release depots for drugs, vitamins and proteins sequestered within the hydrophobic layers or hydrophobic core of the liposome.
Successful use of liposomes as drug-carriers has been limited because the researchers attempting such use have encountered several problems. For example, liposomes are known to act as powerful immunological adjuncts to entrapped antigens and caution must be exercised when enzymes or other proteins of xenogenic origin are entrapped in the liposomes. Also, the rate of diffusion of the drug is difficult to control. This is a function of the inherent instability of the liposomes and the presence of certain blood components which accelerate diffusion of certain drugs. In addition, by their nature, some substances are poorly entrapped in liposomes and therefore diffuse rapidly in circulation. Finally, there has been a problem targeting any cells or organ other than the liver or spleen. An excellent review of liposomes, substances which have been incorporated into liposomes, and the problems associated with use of liposomes as drug carriers is "Liposomes" by Gregory Gregoriaidis, found in Drug Carriers in Biology and Medicine, Chapter 14, 287-341 (Academic Press, N.Y., 1979).
While much has been reported concerning attempts to use liposomes as drug carriers, little has been disclosed concerning the use of liposomes for purposes of increasing shelf life of therapeutic peptides or proteins by stabilizing the structure of the peptide and/or protein. In PCT/US90/05163, entitled, "Therapeutic Peptides and Proteins", Hostetler, et al. disclose use of empty liposomes as a pharmaceutically acceptable diluent to solubilize polypeptides and/or proteins in order to prevent accumulation of the polypeptides and/or proteins at an air/water interface, and to prevent adsorption of the polypeptides and/or proteins to container surfaces. Hostetler et al. disclose that negatively charged phospholipid may be added up to about 50 mole percent, and that phosphatidylcholine, a neutral phospholipid, is the preferred liposome. Hostetler et al. do not disclose a diluent shown to stabilize the structure of a polypeptide and/or protein.
In PCT/US91/07694, entitled, "Preparation and Characterization of Liposomal Formulations of Tumor Necrosis Factor", Hung et al., a lipophilic modified tumor necrosis factor (TNF) molecule in association with the surface or encapsulated within a liposome is described. The liposomal lipophilic TNF molecules are reported to have enhanced in vivo stability. Stability referred to a decrease or a decreased tendency of the TNF-liposome to leak TNF into the system in vivo. The preferred liposomes were neutral lipids. Hung et al. do not disclose a TNF composition wherein the excipients have a stabilizing effect on the structure of the protein.
Nothing can be drawn from the literature concerning contacting a protein, e.g. G-CSF or MGDF, with a negatively charged lipid vesicle thereby directly stabilizing the protein against thermally-induced aggregation, denaturation, loss of activity, and unfolding of the secondary structure. The need exists for such compositions which provide the benefit of being useful in formulation procedures requiring high temperatures (e.g. incorporation of G-CSF and/or MGDF into polymers) as well as being used as novel delivery vehicles (e.g. oral administration of pegylated G-CSF). The present invention provides such compositions.

Stable protein: phospholipid compositions and methods