In a motor unit integrating a motor and a drive control section, the drive control section has a stack structure in which two circuit component containing sections are arranged three-dimensionally with a bus bar being arranged between both containing sections. A printed wiring board on which signal system circuit components, e.g., a rotation sensor and a position sensor, are mounted is arranged in the first circuit component containing section. Power system circuit components, e.g., a FET and a relay, are arranged in the second circuit component containing section. The power system circuit components are mounted directly on the bus bar and are arranged substantially in parallel with the printed wiring board, with the bus bar interposed therebetween. The circuit component containing section is arranged on the outer surface side of the unit with respect to the circuit component containing section, and a heat sink is fixed to the outside thereof.

Conventionally, in a windshield wiper unit for wiping the front glass of a car, a system that activates a wiper arm by a link mechanism with a motor used as a drive source has been widely employed. As the function of the wiper system becomes more refined, a system that electrically controls a motor to thereby control the wiper movement has widely appeared in recent years in place of the above link drive system. In this motor control drive system, a configuration in which a control circuit and motor are integrated with each other is adopted in terms of product modulation or the like. For example, as disclosed in PCT Application Laid-open Publication No. 2002-511038, a motor is mounted in an automobile as a unit including a speed reduction mechanism.
In such a motor unit, however, a control circuit section is two-dimensionally arranged in a housing, and circuit components are two-dimensionally placed on the control circuit section, thereby increasing an area occupied by the mounted circuit components. Further, in the control circuit section, power system components such as a power MOSFET and relay, are all arranged on the printed wiring board, so that the width of a copper-foil pattern must be widened on the printed wiring board according to the current amount, correspondingly increasing the board size. It is desirable that the power system components be arranged on the large-sized printed wiring board in consideration of the heat radiation properties thereof. Even in view of this, the board size tends to be increased. Accordingly, the size of the control circuit section is likely to be increased for these reasons to thereby increase the size of the motor unit. The larger the size of the motor unit, the larger the size of the required mounting space for the unit to be provided on the automobile side becomes, and this problem does need to be solved.
An object of the present invention is to reduce the space occupied by the control circuit section in the motor unit to reduce the size of the entire motor unit.

Motor unit including integrated motor and speed reduction mechanism


A modulation and coding scheme for a communication system is based on use of nonsystematic repeat-accumulate codes for encoding channel information for transmission, and for employing a combined detection and decoding arrangement to decode the coded channel information. The nonsystematic repeat-accumulate codes may be generated by an encoder at a transmitter and decoded by a composite detector/decoder arrangement at a receiver.

1. Field of the Invention
The present invention relates to the use of nonsystematic repeat-accumulate codes in a communication system.
2. Description of Related Art
Wireless communication systems that use multiple antennas at the transmitter and multiple antennas at the receiver, so-called multi-input multi-output (MIMO) systems, can achieve dramatically improved capacity compared to single antenna systems, i.e., systems that have a single antenna at the transmitter and a single antenna at the receiver. In a general MIMO wireless communication system, a data stream to be transmitted is processed, using well-known techniques, to form space-time coded signals that are transmitted over a plurality of different transmit antennas.
The signals emanating from the transmit antennas arrive at receive antennas as a superposition of each of the transmitted signals. Though the transmitted signals interfere with each other, received signals are processed in the receiver to separate out and decode these super-positioned signals. The receiver typically uses a MIMO detector and channel decoder several times over in an effort to reduce the number of bit errors in the decoded signal.
The channel coding used to code signals of the data stream to form the space-time coded signals is used at the receiver for error correction. That is, the channel decoder at the receiver may be able to recover bits that arrive at the receiver in error, due to noise and/or interference. Conventionally, a strong channel code, such as a turbo code, has been used. However, research has shown that an increase in the strength of the channel code does not necessarily result in a reduction in the errors in the decoded signal at the receiver when the number of antennas at the transmitter is larger than the number of antennas at the receiver.
Co-pending and commonly assigned U.S. patent application Ser. No. 10/180,727, filed Jun. 26, 2002 and entitled "MIMO SYSTEMS HAVING A CHANNEL DECODER MATCHED TO A MIMO DETECTOR" describes the use of low density parity check codes (LDPC) codes as channel codes in a communication system where the receiver has a MIMO detector, particularly when the number of transmit antennas is larger then the number of receive antennas. LDPC codes can be adjusted to change decoding properties so that a LDPC code decoder at the receiver may be designed having a transfer characteristic curve that is matched to the transfer characteristic curve of a MIMO detector.
The transfer characteristic curve may be defined as a curve that shows extrinsic mutual information content of soft value bits (bits whose value conveys both whether the bit is a one or zero and an indication of the certainty with which this is known) at an output of a device (such as a channel decoder) determined as a function of the mutual information content of soft value bits at the input of the device. A transfer characteristic curve may be illustrated with extrinsic information transfer (EXIT) charts, bit error rate (BER) charts or signal to noise ratio (SNR) charts, as is known in the art.
Repeat-accumulate (RA) codes have recently been devised as a competitive alternative to parallel concatenated (PC or turbo) and LDPC codes. RA codes are encoded by using four types of operations, in the following order: variable rate repetition encoders, an interleaver, variable rate modulo-2 adders (single parity check encoders), and an accumulator. The general structure is described in a paper by H. Jin, et al., entitled "Irregular repeat-accumulate codes," in Proc. 2nd Int. Symp. On Turbo Codes, Brest, France, 2000. In the context of multi-input, multi-output (MIMO) systems, both LDPC and RA codes can operate near capacity of the system. One type of irregular RA codes are known as nonsystematic repeat-accumulate (RA) codes. Nonsystematic RA codes are a developing family of iteratively decodable channel codes that can operate close to capacity for many channels.

Nonsystematic repeat-accumulate codes for encoding and decoding information in a communication system


A weed eradicating substance, and a desalination substance. A method of use includes irrigating the soil with water, prior to planting, to cause the germination of weed seeds, and thereafter applying a desalination agent to increase weed seed germination. An application of the inventive pesticide then causes a much larger number of weeds to be eradicated.

The presence of salts, and other unwanted substances, in soils, such as agricultural soils, and their adverse effects on plant proliferation, have long been recognized. The salts, such as chlorides, carbonates and sulfates of sodium, potassium, calcium and magnesium, are often already present in the soil, prior to planting. In addition, in some cases, salts are introduced into the soil through the use of irrigation water.
In general, the effect of salts on plants is indirect. In this regard, the salts adversely affect osmotic water potential with a resulting reduction in uptake of water by germinating seeds and the roots of established plants. The presence of salts in soils can result in a fewer number of seeds becoming properly established. Also, there can be an undesirable delayed rate of seed establishment, as well as an impairment in the growth of established plants.
Due to such severe adverse effects of salts on plants, it has been long recognized that compositions and methods of using the same, capable of reducing such adverse influences would have great utility. Important advances in the art are the methods and compositions disclosed in U.S. Pat. Nos. 4,687,505 and 4,923,500, as well as in the foregoing mentioned U.S. patent applications.
With regard to the above mentioned patents, there is disclosed techniques for the application of certain anionic materials, or their substantially neutral water soluble salts, to soil in minute amounts, for reducing the harmful effects of salts which had accumulated in the soil from irrigation water, or which were previously present in the soil. In this manner, salts were leached from the soil by the application of a liquid, such as irrigation water. These patented compositions are effective because large areas of soil are treated, prior to planting, by the addition of the anionic materials to irrigation water or by other methods of application applied to the fields generally.
Such patented methods and compositions are highly effective in reducing soil salinity, and have proven to increase plant proliferation and quality as well as increased yield when used in crop production. Of course, other soil conditioning products are required to facilitate plant growth. Water and fertilizer are also used to help plant proliferation. Such substances help to nourish the plants, so that they can grow in a healthy and vigorous manner. However, in some situations, conventional fertilizers may not be entirely satisfactory for facilitating adequate nourishment uptake by plants. In such situations, the plants may not be able to thrive in a vigorous and healthy manner, even when conventional fertilizers are applied. In order to overcome such an inadequate nourishment problem, improved fertilizers have been developed. For a description of such an improved fertilizer, reference may be made to the foregoing U.S. patent application, Ser. No. 709,837, filed Jun. 4, 1991.
In addition to the foregoing mentioned impediments of unwanted salt and inadequate nourishment uptake, the presence of weeds and germinating weed seeds in soil, such as agricultural soils, can cause an adverse affect on plant proliferation. The weeds, and weed seeds, are often already present in the soil, prior to planting. Subsequent to planting, when irrigation water and fertilizers are applied, the weeds compete with the desired plants and, in general, can rob the desired plants of nutrients necessary for root establishment and healthy plant growth. Thus, weeds directly compete with the desired plants for the assimilation of essential nourishment, and the presence of weeds and weed seeds can cause directly the reduction of the quantity, and the quality, of the desired plants.
In addition, at the time of harvesting, the presence of the unwanted and undesirable weeds presents more difficulties for the grower. In this regard, methods have to be adopted for either removing the weeds before harvesting, or for removing the weeds from the crop, after harvesting. The weed removal is often labor intensive and, as a result, both expensive and time consuming.
In view of the foregoing, it is clear that the presence of weeds and weed seeds, in agricultural or other planting soils, can cause substantial economic loss to growers, both by reduction of yields and by increased labor costs for weed removal. Thus, it has long been recognized that compositions and methods for weed control have significant economic value. Because of the well recognized need for such compositions and methods, various herbicidal compositions have been developed. In some cases, when such a composition is applied properly to a moist soil, the liquid is converted into a gaseous in-ground fumigant for controlling both weeds and germinating weed seeds. In addition, some known herbicides have utility for controlling nematodes and other soil-borne diseases such as Rhizoctonia, which also, of course, adversely impact plant growth.
Prior known herbicides, and conventional methods of using them, are effective in reducing weed populations in soils and thereby increasing plant proliferation and plant quality, as well as increased yield. However, for some applications and under certain growing conditions, these known herbicides have not performed in an entirely satisfactory manner. Thus, for a variety of reasons, more effective herbicides for the control of weeds and weed seeds in planting soil is highly desirable.
In order to illustrate the problem, it is well recognized by those skilled in the art that some weeds, especially nutgrass, are especially difficult to control. It has been found, for example, that even after a proper application of a known herbicide to agricultural soils, the number of weeds eradicated generally does not exceed approximately 80 percent. Thus, in many instances, about 20 percent of the weeds remain in the field, after conventional herbicide treatment. Such a percentage of a remaining number of weeds, is known to be undesirable and unwanted in many agricultural growing situations. In this regard, with such a high percentage of the weeds surviving, the desired crop is often so adversely affected that the crop yield and quality are generally acceptable.
In view of the foregoing, it would be highly desirable to have an improved pesticide, which will serve as a more effective composition eradicated weeds and weed seeds to facilitate increased plant proliferation. In addition, it would be highly advantageous to facilitate significantly, the early, as well as effective, eradicated and control of weeds so that a much higher percentage of weeds can be killed. In this regard, such a product would be most effective for early and rapid weed and weed seed control, thereby facilitating early root establishment and nutrient uptake in desirable plants.
Such an improved pesticide and method of using it, would serve to control more quickly and effectively the proliferation of weeds competing for nourishment with the desired plants. With such a more rapid and effective weed controlling composition and method of using it, the desired plants can proliferate more readily, since it is important for the germination and establishment of plants to become properly nourished immediately with as little interference as possible from adverse influences, such as weeds.

Pesticide and method of making and using same


A sustained release formulation as a unit dose contains 100 mg-1000 mg of Acetaminophen and 15 mg-150 mg of tramadol hydrochloride, which comprises of 1) an immediate release portion comprising of 25%-75% of the total effective amount of drug in the dosage form and 2) a sustained release portion comprising of a) 25%-75% of the total effective amount of drugs in the dosage form; b) 6%-50% of gelling polymers of the total formulation, and c) optionally an enteric coating at a level of 5%-40% of the total formulation. The set forth formulation dissolves 25%-60% of the total drug in the first hour, 50%-90% of the total drug in the first four hours and not less than 80% of the total drug in the first 12 hours using USP dissolution method II at 50 rpm.

Acetaminophen with Codeine Phosphate (Tylenol® with Codeine) or Hydrocodone Bitartrate (Vicodin®) or Oxycodone (Tylox®) is commonly used analgesic drugs, indicated for the relief of moderate to moderately severe pain. Acetaminophen with Codeine or Hydrocodone combines the analgesic effects of a centrally acting analgesic, codeine or hydrocodone, with a peripherally analgesic, acetaminophen. Opioids have for many years been used as analgesics to treat severe pain. They, however, produce undesirable side effects and as a result cannot be given repeatedly or at high doses. The side effect problems are well documented in the literature (J. Jaffe and W. Martin in chapter 15, "The Pharmacological Basis of Therapeutics", editors L. Goodman and A. Gilman, 5th Edition, 245, 1975), which discloses that morphine and its congeners, e.g., codeine, hydrocodone and oxycodone, are opioid agonist analgesics that exhibit side effects such as respiratory depression, constipation, tolerance and abuse liability.
As alternatives to using opioids, non-opioids such as acetaminophen (APAP) and aspirin are used as analgesics. APAP, like aspirin, is not subject to the tolerance, addiction and toxicity of the opioid analgesics. However, APAP and aspirin are only useful in relieving pain of moderate intensity, whereas the opioid analgesics are useful in relieving more intense pain; See Woodbury, D. and Fingl, E. in "The Pharmacological Basis of Therapeutics", 5th Ed.; Goodman, L. and Gilman, A., Chapter 15, pages 325 (1975).
To reduce the side effect problems of opioids, opioids have been combined with other drugs including non-opioid analgesic agents, which lowers the amount of opioid needed to produce an equivalent degree of analgesia. It has been claimed that some of these combination products also have the advantage of producing a synergistic analgesic effect. For example, A. Takemori, Annals New York Acad. Sci., 281, 262 (1976) discloses that compositions including combinations of opioid analgesics with drugs other than analgesics exhibit a variety of effects, i.e., subadditive (inhibitory), additive or superadditive. R. Taber et al., J. Pharm. Expt. Thera., 169(1), 29 (1969) disclose that the combination of morphine and methadone, another opioid analgesic, exhibits an additive effect. U.S. Pat. No. 4,571,400 discloses that the combination of dihydrocodeine, an opioid analgesic, and ibuprofen, a non-opioid analgesic, provides superadditive effects when the components are within certain ratios. A. Pircio et al., Arch. Int. Pharmacodyn., 235, 116 (1978) report superadditive analgesia with a 1:125 mixture of butorphanol, another opioid analgesic, and acetaminophen (APAP), a non-opioid analgesic, whereas a 1:10 mixture did not show any statistically significant superadditive analgesia.
An immediate-release tablet composition comprising a tramadol material and acetaminophen, and its use, was invented (U.S. Pat. No. 5,336,691). The usual adult dosage is one or two tablets (Ultracet™) every four to six hours. The compositions are pharmacologically useful in treating pain and tussive conditions. The compositions are also subject to less opioid side-effects such as abuse liability, tolerance, constipation and respiratory depression.
The benefits of sustained release dosage forms are well documented. To reduce the dose segment and increase the patient compliance is one of the purposes with sustained release formulations. It has been reported that sustained release oral solid dosage forms of opioid analgesics are provided as multiparticulate systems which are bioavailable and which provide effective blood levels of the opioid analgesic for at least about 24 hours (see U.S. Pat. No. 6,294,195). Sustained release tablets for acetaminophen may be prepared using coated acetaminophen particles and uncoated acetaminophen particles to compress them to tablets providing a combination of immediate release and sustained release dosage forms (see U.S. Pat. No. 6,126,969). An acetaminophen-sustained release tablet or tablet layer is formed by making a wet granulation, using Povidone (PVP) in water or alcohol-water as the granulating fluid which is mixed with acetaminophen, hydroxyethyl cellulose, a wicking agent e.g. microcrystalline cellulose, then drying and milling the granulation and blending with dry powdered erosion promoter, e.g. pregelatinized starch, wicking agent, lubricant e.g. magnesium stearate and glidant e.g. silicon dioxide, and compressing the resultant granulation, which upon administration results in a slow release of the acetaminophen (see U.S. Pat. No. 4,820,522).
It has previously been known in the art that controlled release compositions of opioid analgesics such as morphine, hydromorphone or salts thereof could be prepared in a suitable matrix. For example, U.S. Pat. No. 4,990,341 (Goldie) describes hydromorphone compositions wherein the dissolution rate in vitro of the dosage form, when measured by the USP Paddle Method at 100 rpm in 900 ml aqueous buffer (pH between 1.6 and 7.2) at 37.degree. C., is between 12.5 and 42.5% (by wt) hydromorphone released after 1 hour, between 25 and 55% (by wt) released after 2 hours, between 45 and 75% (by wt) released after 4 hours and between 55 and 85% (by wt) released after 6 hours.
In the pharmaceutical market today, there are only sustained release dosage forms available for individual analgesic drugs, for example, oxycodone or acetaminophen.

Sustained release formulations containing acetaminophen and tramadol


An adaptive feedback control method is provided for a chemical mechanical polish process to minimize a dielectric layer clearing time difference between two annular regions on a substrate. An optical system with an optical window passes below the polishing pad and detects reflected light interference signals from at least two annular regions. A pre-clearing time difference is determined and is used to calculate an adjustment to one or both of a CMP head membrane pressure and a retaining ring pressure. The pressure adjustment is applied before the end of the polish cycle to avoid the need for a second polish cycle and to reduce a dishing difference and a resistance difference in a metal layer in the at least two annular regions. In some embodiments, a second pressure adjustment is performed before the end of the cycle and different CMP head membrane pressure adjustments are made in different pressure zones.

CMP is a process of removing unwanted conductive or dielectric materials from a substrate by the application of chemical and mechanical forces. For example, during a damascene process, a metal such as Cu is deposited in openings within a dielectric layer. However, excess metal is deposited and must be removed with portions of dielectric material so that a top surface of the dielectric layer becomes coplanar with a top surface of the new metal layer.
A CMP tool is typically comprised of a polishing station with a rotatable platen on which a polishing pad is affixed. A substrate having a front side with one or more layers to be planarized has a backside that is held to a head piece by a vacuum during loading/unloading and by a retaining ring during polishing. After the substrate's front side is brought into contact with the polishing pad, a slurry is introduced and includes a chemical component such as an aqueous base or aqueous acid, and abrasive particles. As the polishing pad is rotated in one direction, the substrate typically rotates in the same direction, and the slurry effectively etches and abrades away a portion of the uppermost layer or layers on the substrate. During a polishing cycle, end point signals from an optical detection system may be analyzed either in real time or off-line to determine the end of the polishing cycle. Moreover, metrology measurements may be taken at the end of a cycle to indicate a final non-uniformity of film thickness across each wafer and may be used to adjust the polish process in subsequent polish cycles.
In some cases, CMP processes require a second polishing cycle where the wafer is reloaded into a CMP tool and non-uniformity thickness data from the initial polish cycle is used to determine backside pressures applied to the wafer in the second polish cycle with the aim of improving the final thickness non-uniformity. Sometimes a second polish is not possible due to a situation where final thickness constraints have already been met after the initial polish. In other words, further polishing of the thicker regions on the substrate cannot occur since the thinner regions that are already at the minimum thickness specification would also be thinned. Therefore, a CMP process that enables pressure adjustments during a single polish cycle is needed to minimize the difference between clearing times between different annual regions at the end of the polish cycle which reduces process time and improves film thickness uniformity across the substrate thereby increasing product yield.

Method for adaptive feedback controlled polishing


A key blank loading cartridge includes a sleeve defining a cavity for holding a stack of key blades within a box of key blanks. The key blanks are releasably retained in the cartridge cavity by their blade portions leaving the head portions of the blanks exposed. After having been removed from the box, the so retained stack of key blanks is ready to be loaded as a single unit in a corresponding key blank magazine. Once the head portions of the key blanks have been engaged in the magazine, the sleeve can be pulled off the blanks and returned to the key blank manufacturer and reused in another key blank shipping package.

A key blank dispenser or magazine has a plurality of key blanks stored therein. At regular intervals, new key blanks must be loaded into the dispenser. The loading process may be cumbersome because the key blanks are typically shipped loose in a box. Hence, the operator or employee must manually align the key blanks and load them in said magazine. To assist in the loading of the key blanks, a manual tool can be used to remove the contents of the box of blanks and load them into the magazine as one unit. While, the manual tool facilitates removal of the blanks from the box, it still necessitates the use of a separate tool. There is, thus, still a need to simplify and expedite the loading operation of the blanks into the magazine.


Embodiments of the invention are directed to methods and compositions of multitype HPV polypeptides.

I. Field of the Invention
Embodiments of this invention are directed generally to biology and medicine. In certain embodiments the invention is directed to compositions and method of using multitype HPV polypeptides.
II. BACKGROUND
Genital-tropic human papillomavirus (HPV) infections are considered the most common sexually transmitted infection in the United States (CDC Report to Congress, Prevention of Genital Human Papillomavirus Infection, January 2004). The major manifestations of anogenital HPV include genital warts (condyloma acuminatum) and intraepithelial neoplasia of the vulva, cervix, anus, or penis. A small fraction of persistent high-risk HPV infections, if left untreated, progresses to cancer. (e.g., cervical cancer, on occasion head and neck cancer, and some types of non-melanoma skin cancer). The presence of HPV DNA has been reported in 99.7% of cervical carcinomas worldwide, suggesting that HPV infection is a necessary cause of this cancer and that this disease can be prevented by prophylactic HPV vaccination (Walboomers et al., 1999).
In addition to genital warts, HPV infection can result in common warts, plantar warts, or planar warts. Warts may exist in different forms depending on the HPV type responsible and the epithelium involved. Common warts (verruca vulgaris) usually occur on the hands, as flesh-colored to brown, exophytic, and hyperkeratotic papules. Plantar warts (verruca plantaris) occur on the soles of the feet and can be quite painful. They can be differentiated from calluses by removing the surface layer to reveal thrombosed capillaries. Flat or planar warts (verruca plana) are most common among children and can occur on the face, neck, chest and flexor surfaces of the forearms and legs.
Approximately 35 of the more than 100 subtypes of HPV are specific for the anogenital epithelium and have varying potentials for malignant transformation (Munoz et al., 2003). Of the 15 oncogenic genital HPV types, HPV16 is the most common, followed by HPV 18 and HPV45 (contributing ˜50%, ˜20% and ˜10% of cervical cancer cases, respectively). Despite the successes of public health efforts to reduce the incidence and mortality of cervical cancer with the implementation of cervical cytology screening programs, women who do not undergo regular screening account for most of the patients with invasive cancers (Hoffman and Cavanagh, 1995) and cervical cancer remains the second most common cause of cancer death in women worldwide and the most prevalent cancer in women of sub-Saharan Africa, Central America, south-central Asia and Melanesia (a subregion of Oceania extending from the western side of the West Pacific to the Arafura Sea, north and northeast of Australia; the term was first used to denote an ethnic and geographical grouping of islands distinct from Polynesia and Micronesia) (Parkin, 2001). Approximately 471,000 cases of invasive cervical carcinoma are diagnosed annually (Parkin, 2001).
The HPV genome is surrounded by a 60-nm, non-enveloped icosahedral capsid (Baker et al., 1991) which contains the two genetically-unrelated major capsid protein L1 and the minor capsid protein L2. Recombinant L1 self-assembles into virus-like particles (VLPs) which are morphologically and immunologically similar to native virions (Kirnbauer et al., 1992). L1 VLP-based vaccines are highly protective against infection corresponding to the papillomavirus type used to derive the immunogen (homologous vaccine), but are ineffective against all but the most closely related HPV types (Roden et al., 2000). Licensed HPV vaccines have circumvented this obstacle by designing multivalent vaccine preparations; CERVARIX™ contains L1 VLP derived from HPV16 and HPV18, while GARDASIL™ also contains HPV6 and HPV11 L1 VLPs for prevention of benign genital warts. Unfortunately, the expense and the need for refrigeration of these L1 VLP vaccines currently renders them impractical for use in low resource and remote areas where they are most needed. Furthermore, because these vaccines are ineffective against a significant fraction of oncogenic HPV types, costly cytologic screening programs remain necessary. To realize the full potential of HPV prevention globally, the vaccine should be safe and effective, stable at ambient temperature to facilitate delivery in remote locations, inexpensive to manufacture, and administered without needles, preferably available in a single dose formulation. The disease burden resulting from the plethora of HPV types suggest that a broadly protective vaccine is necessary. Thus, there is a need for additional cross-neutralizing HPV vaccines.

Multitype HPV peptide compositions and methods for treatment or prevention of human papillomavirus infection


Operation for each action of a machine is individually controlled by providing a file of set of components necessary to carry out the operation and a file of a set of components that are available and then determining in sequence whether each required component is also available and transferring those components that are both required and available in sequence to a fault file. The fault file may then be read in sequence and used to control the action being controlled so that if anyone of the required components is not available, the fault file so indicates and terminates the operation based on the first component found to be inoperative so that it is an easy matter to define the source of the problem.

Generally, the control system for controlling the operation of equipment, particularly complicated equipment where a number of different elements must start-up in sequence in order to achieve a desired output require a relatively complicated controls to ensure that the required elements are components of the system are operative.
Systems are known to maintain the machine or equipment on target, e.g. computer controls that measure or estimate trajectory error and adjust the controlled system to ensure it follows more closely a designated path or trajectory.
U.S. Pat. No. 5,222,017 issued Jun. 22, 1993 to Yellowley et al. describes a computer control system that incorporates a plurality of slaves and a flagging system that influences the operation when any one of the monitored conditions reaches an unacceptable level. Again, this system is primarily used for machine control maintaining a required trajectory as opposed to machine or module start-up and identification of unavailable or faulty components


A clock data recovery (CDR) circuit to recover a clock signal and data signal from an input signal. The CDR circuit includes a control circuit, a select circuit and a phase adjust circuit. The control circuit generates a first control signal according to a phase relationship between the input signal and a first clock signal. The select circuit is coupled to receive the first control signal from the control circuit and coupled to receive a second control signal. The select circuit is responsive to a select signal to select either the first control signal or the second control signal to be output as a selected control signal. The phase adjust circuit is coupled to receive the selected control signal from the select circuit, the phase adjust circuit being responsive to the selected control signal to adjust the phase of the first clock signal.

Clock data recovery (CDR) circuits are often used in high speed signaling applications to recover clock and data signals from a signal line. Typically, transitions in an incoming signal are detected and used to generate a clock signal which is used, in turn, to sample data in the incoming signal.
FIG. 1 illustrates a prior art integrated circuit device 101 that includes a number of CDR circuits, CDR0–CDRN-1, to recover clock and data signals from lines DATA0–DATAN-1, respectively. Each CDR circuit includes a receiver 102 and a clock generator 103. The receiver 102 captures a number of samples of the incoming signal during each cycle of the recovered clock signal 104. The samples are compared with one another within a phase control circuit 107 (shown in the detail of clock generator 103 of CDR0) to determine whether transitions in the incoming signal occur early or late relative to edges of a recovered clock signal 104. Based on the early/late determination, the phase control circuit 107 outputs a control signal to a phase adjust circuit 105 which responds by advancing or delaying (i.e., retarding) the phase of the recovered clock signal 104. Eventually, each of the CDR circuits reaches a phase locked condition in which the recovered clock signal 104 has a desired phase relationship to the incoming data signal (e.g., the recovered clock signal becomes aligned with the midpoint of the data eye), and the phase control output begins to toggle between advancing and delaying the phase of the recovered clock signal 104.
One disadvantage of the CDR arrangement in the integrated circuit 101 is that each of the signals on lines DATA0–DATAN-1 usually must undergo some minimum number of transitions per unit time (i.e., have a minimum transition density) in order for the corresponding CDR circuit to remain phase locked. Because the data content of the incoming signal may include relatively long sequences of zeroes or ones which lack such transitions, encoding, such as 8b/10b encoding, is often performed to replace the incoming data with codewords that meet the minimum transition density requirement. Because the codewords typically include more bits than the data values they replace, signal encoding tends to consume bandwidth on the signal line that could otherwise be used to transmit data. For example, in the case of 8b/10b encoding, each eight-bit data value is replaced with a 10-bit codeword, so that the encoding scheme consumes 20% of the signal line bandwidth. Other data encoding schemes also tend to consume signal line bandwidth.

Clock data recovery with selectable phase control


According to the invention, there is provided null-LOX-1 barley and plant products produced thereof, such as malt manufactured by using barley kernels defective in synthesis of the fatty acid-converting enzyme lipoxygenase-1. Said enzyme accounts for the principal activity related to conversion of linoleic acid into 9-hydroperoxy octadecadienoic acid, a lipoxygenase pathway metabolite, which—through further enzymatic or spontaneous reactions—may lead to the appearance of trans-2-nonenal. The invention enables brewers to produce a beer devoid of detectable trans-2-nonenal-specific off-flavors, even after prolonged storage of the beverage.

One of the research goals related to modern beer production is determining the molecular factors for beer quality and stability. A large fraction of beer is produced on the basis of barley (Hordeum vulgare, L.). It is a monocotyledonous crop plant grown in many parts of the world, not only due to its economic importance as a source of industrial products, such as beer, but also as a source of animal feed. The United States is now one of the leading producers of malting barley, with around 13% of the world crop; Canada, Australia and Europe together account for about 70% of the production (Bios Intern., 2001).
A continuing effort of barley breeders is to develop stable, high-yielding cultivars that are agronomically sound. To accomplish this goal, attempts have included random mutagenesis by chemical treatment or irradiation to modify traits of interest, for example to alter the expression of specific genes that may have deleterious effects on plant growth and crop productivity in general—but also on traits conferring added quality to a product manufactured from the crop. It is well established that sodium azide, NaN3, is a useful chemical to mutagenize barley. Specifically, NaN3-derived mutagenesis has been used to induce genetic changes in barley to generate mutants blocked in the synthesis of anthocyanins and proanthocyanidins (von Wettstein et al., 1977; von Wettstein et al., 1985; Jende-Strid, 1991; Jende-Strid, 1993; Olsen et al., 1993). A second example relates to barley kernels mutagenized with NaN3 to screen for high levels of free phosphate with the aim to identify low-phytate mutants (Rasmussen and Hatzak, 1998); a total of 10 mutants out of 2,000 screened kernels were identified. Although a major drawback in barley genetics has been the inability to specifically study gene function through reverse genetics, forward genetic screens—e.g. following NaN3-induced mutagenesis—continue regarding improvements that relate to nutritional and product quality parameters of barley and malt.
Except in a gross and general fashion, a breeder cannot predict the outcome of new plant lines under development in a conventional plant breeding process. This unpredictability is mainly caused by the lack of control at the cellular level, more specifically at the level of nuclear DNA—the complexity of which is enormous. A number of other factors influence the outcome of a plant breeding process, for example the climate and soil quality at the geographical location of plant propagation. As a result, different barley breeders that use conventional techniques will never develop plants with identical traits. In the conventional breeding process, a most difficult task is the identification of plants that are genetically superior, not only with respect to the trait of interest, but also with respect to physiological issues of relevance for plant growth. The selection process is particularly difficult when other confounding traits mask the trait of interest. When present-day plant breeding procedures include DNA sequence determination of the mutated gene, it is at a late stage of the breeding program—i.e. after mutant characterization, for example as recently described for screening of chemically induced mutations in Arabidopsis and other plants (Colbert et al., 2001).
Thus far, the creation of gene-indexed loss-of-function mutations on a whole-genome scale has been reported for the yeast Saccharomyces cerevisiae (Giaever et al., 2002). For the plant Arabidopsis, 21,700 of the ˜29,454 predicted genes have been inactivated by the insertion of Agrobacterium T-DNA sequences (Alonso et al., 2003).
Until now, it is not unusual that a conventional breeding process from the first mutagenesis or crossing to marketing of plants or seeds takes >10 years. Specifically, it would be excellent to provide the plant breeder with methods to detect mutations in the gene related to the trait of interest. Such improvements would enhance the level of predictability in breeding programs, especially when the selection of mutants is directed toward those having nonsense mutations in the protein-coding part of the gene of interest. In other cases, it may also be preferred with an early identification of DNA mutations, for example to cancel further breeding with lines characterized by promoter mutations in the gene of intererest or where other DNA mutations influence expression—simply because environmental or physiological factors could confer reversion of the trait induced by the mutagen. Accordingly, there is a demand for finding alternative ways of detecting mutations of interest early in the breeding program. This should make the entire breeding process faster and economically of higher interest, thus maximizing the amount of grain produced on the land.
A major proportion of the barley produced comprises malting varieties, the kernels of which are converted to malt through processes of controlled steeping, germination, and drying of the barley. A small proportion of the malt is used as ingredients in the food industry, whereas the majority of the malt is subsequently used as the main ingredient in the production of malt-derived beverages, including, but not limited to, beer and whisky. In the brewhouse, milled malt is subjected to a mashing process comprising a step-wise increase in temperature of a malt-water suspension which confers partial, enzymatic degradation and extraction of, for example, the kernel polymers starch and β-glucan. Following filtration, the aqueous mash is boiled with hops to yield the wort. Said wort is subsequently fermented with yeast, giving the beer product which—upon maturation—is bottled. The wort can also be used for the production of non-fermented malt beverages.
Palatability and flavor stability of a beverage is an important factor of relevance to the composition of barley and malt. This is because natural flavor molecules derived from said barley and malt—or generated by the action of enzymes extracted from said barley and malt—may confer undesirable taste characteristics to the final product (Drost et al., 1990). In this respect, formation of the volatile compound giving a cardboard-like flavor appears to be of particular biochemical as well as economic interest. In 1970, the molecule responsible for cardboard-like flavor was isolated and identified as T2N, a nine-carbon (C9) alkenal (Jamieson and Gheluwe, 1970). Since the taste-threshold level for T2N in humans is extremely low, previously determined to be around 0.7 nM or 0.1 ppb (Meilgaard, 1975), products with even minute levels of the aldehyde are regarded as being aged due to the off-flavor taste of the product. Moreover, liberation of T2N from decomposing T2N adducts during beer storage may cause deterioration of the product (Nyborg et al., 1999).
Radioactive labeling studies with plant tissue established that nonenals are derived from the C18 fatty acid linoleic acid, whereas the hexanals and nonadienals are formed from the C18 fatty acid linolenic acid (Grosch and Schwartz, 1971; Phillips and Galliard, 1978). These and numerous subsequent observations—for example as summarized by Tijet et al. (2001), Noordermeer et al. (2001), and Matsui et al. (2003)—have been interpreted as evidence that T2N is formed by the sequential action of LOX pathway-specific enzymes, with the action of LOX representing an early enzymatic step. Consistent with this notion, Kurodo et al. (2003) found that malt contains a heat-stable enzymatic factor which is necessary for the transformation of the products made by LOX into T2N. The barley kernel contains three LOX enzymes known as LOX-1, LOX-2 and LOX-3 (van Mechelen et al., 1999). While LOX-1 catalyzes the formation of 9-HPODE—a precursor of T2N—from linoleic acid, LOX-2 catalyzes the conversion of linoleic acid to 13-HPODE which is further metabolized to hexanal (FIG. 1B), a C6 aldehyde with a taste threshold level of around 0.4 ppm (Meilgaard, supra). Although the product specificity of LOX-3 remains elusive, the very low expression level of the corresponding gene, as shown by van Mechelen et al. (supra), suggests that its contribution to T2N formation is negligible. Research is ongoing to determine if LOX activity is the sole enzymatic source for the generation of linoleic acid hydroperoxide precursors of relevance for the formation of the T2N-specific off-flavors, or whether the process of fatty acid autooxidation contributes as well. It is notable that C18 hydroperoxides can be further converted by more than seven different families of plant and animal enzymes, with all reactions collectively called the LOX pathway (Feussner and Wasternack, 2002); this pathway is also referred to as the oxylipin pathway. Oxylipins, as their name implies, are oxygenated lipid-derived molecules, which result from the oxygenation of unsaturated fatty acids via the LOX reaction and also include any molecules derived from such oxygenated molecules.
Barley kernels and barley plants having a LOX-1 protein characterized by reduced activity were disclosed in PCT application PCT/IB01/00207 published as WO 02/053721A1 to Douma et al. However, said application does not teach the generation and analysis of barley kernels with inactive LOX-1 enzyme.
Several examples on mutated plants that synthesize low levels of LOX are known. For example, three soybean lines were identified in the early 1980s, each deficient in one of the three LOX enzymes in mature soybean seed:                (i) LOX-1. Although the molecular basis of the LOX-1 null mutation remains uncertain, it correlates with the absence of the corresponding mature mRNA (Hildebrandt and Hymowitz, 1982; Start et al., 1986);        (ii) LOX-2. Transcripts for the mutated gene were detected, and a single base change was observed which replaces a histidine ligand to the active site iron, leading to enzyme instability (Davies and Nielsen, 1986; Wang et al., 1994);        (iii) LOX-3. LOX-3 null mutants exhibited no detectable levels of the corresponding transcript, probably as a consequence of cis-acting elements in the gene promoter (Kitamura et al., 1983; Wang et al., 1995).
In pea seed, a null-LOX-2 line was found to carry a defect leading to the absence of most LOX-2 protein (Forster et al., 1999). Since this line exhibited a great decrease in the amount of mRNA for LOX-2, it was suggested that the mutation caused a dramatic reduction in mRNA stability.
In rice, immunoblot screening of extracts revealed the presence of two natural cultivars, Daw Dam and CI-115, each lacking one of three LOX enzymes (Ramezanzadeh et al., 1999). It was determined that the amount of hexanal, pentanal, and pentanol in normal rice with all three LOXs was markedly induced during storage, while that in Daw Dam and CI-115 was reduced in the range from 66% to 80%. Despite that the results suggest the absence of LOX enzymes in rice grains alleviate oxidative deterioration, the molecular determinants which impart the LOX-less characteristics of Daw Dam and CI-115 remain elusive.
Both antisense-mediated and co-suppression-mediated transgenic depletion of genes for LOX have proved useful to elucidate the function of specific LOX enzymes and their corresponding products in plant defense signaling. In Arabidopsis, for example, depletion of a LOX enzyme led to a reduction in the wound-induced accumulation of jasmonic acid (Bell et al., 1995). And results of antisense-mediated depletion of a gene encoding LOX established the involvement of the corresponding enzyme in the incompatibility trait of a tobacco plant resistant to a fungal pathogen (Rancé et al., 1998). A third example where transgenic approaches have been used to elucidate LOX functions relates to the role of a potato LOX, denoted LOX-H1, in growth and development of potato plants (León et al., 2002). It was shown that LOX-H1 depletion resulted in a marked reduction of volatile aliphatic C6 aldehydes, compounds involved in plant defense responses and acting as either signaling molecules for wound-induced gene expression or as antimicrobial substances. A further study showed that transgenic potato plants depleted in the expression of a gene for a LOX enzyme exhibited abnormal tuber development (Kolomiets et al., 2001). However, specific oxylipins that accounted for the tuber phenotype were not identified. In another study, antisense-mediated depletion of potato LOX-H3 suppressed the inducible defense response of the plant, concominant with a higher tuber yield (Royo et al., 1999). Collectively, these data suggest that expression of genes encoding LOX enzymes is important in plant development, possibly with some LOX enzymes playing a defensive role against pathogens, whereas other LOX enzymes generate products that may act to regulate cell development.
It is also of importance to note that tomato fruits with 2-20% reduced levels of two LOX enzymes showed no significant changes in flavor volatiles when compared to wild-type fruits (Griffiths et al., 1999). This finding suggests that either very low levels of LOX are sufficient for the generation of aldehydes and alcohols, or that other LOX enzymes are active in the generation of these compounds.
The role of LOX enzymes is also related to issues outside the field of manufacturing beer, such as LOX-catalyzed generation of hydroperoxy fatty acids that inhibit mycotoxin formation in plants susceptible to fungal contamination, for example as disclosed in U.S. Pat. No. 5,942,661 to Keller. Although the role for LOX enzymes in plant defense and wounding responses remains less clear, the enzymes are induced upon wounding and pathogen challenge (Bell and Mullet, 1991; Bell and Mullet, 1993; Melan et al., 1993; Sarvitz and Siedow, 1996). LOX enzymes' role in wounding and plant defence could be to produce reactive fatty acid hydroperoxides against pathogens (Rogers et al., 1988). Alternatively, LOXs may be induced by stresses to produce signal molecules, such as methyl jasmonate (Bell et al., supra).
Strategies have also been described where 13-HPODE, produced by the action of a LOX enzyme, acts as a substrate for hydroperoxide-converting enzymes to produce flavor-active aldehydes (Noordermeer et al., 2002; Husson and Belin, 2002). Similar processes are disclosed in numerous patents, e.g. U.S. Pat. No. 6,150,145 to Häusler et al. and U.S. Pat. No. 6,274,358 to Holtz et al.
Also, LOX enzymes have been shown to contribute several beneficial effects to bread-making (Casey, 1997). Moreover, U.S. Pat. No. 6,355,862 B1 to Handa and Kausch discloses that fruit quality can be enhanced by inhibiting production of LOX, such as giving a longer shelf life to the product.

Barley for production of flavor-stable beverage


A ROM containing a variable length coding table for a 2 picture element range is provided. A motion vector within the range of 2 picture elements is provided to the ROM to produce a VLC code corresponding to the motion vector within the range of 2 picture elements. In a calculation circuit, assuming that the value of a motion vector within the range of 4 picture elements is X, a quotient Y and a remainder Z are obtained by the division of X by 2. The quotient Y is supplied to the ROM and the output of the ROM is added the remainder Z at an addition circuit to obtain a VLC code corresponding to the motion vector lying within the range of 4 picture elements. This is equivalent to variable length coding for a 4 picture element range. By transmitting a flag indicating whether the motion vector range is 2 picture elements or 4 picture elements, the motion vector is correctly reproduced from the VLC code. Accordingly motion vectors within the ranges of 2 picture elements and 4 picture elements can be coded using a single ROM table so that the hardware requirements are reduced.

1. Field of the Invention
The invention relates to a variable length coding apparatus and method for motion vectors to be used in highly efficient coding of a moving picture signal, on the basis, for example, of interframe correlation.
2. Description of the Prior Art
When coding which utilizes interframe correlation is performed in connection with highly efficient coding of a moving picture signal, differences between frames are coded and, a motion vector is used to account for movement between two frames.
More specifically, a picture is divided into blocks of a predetermined size (for example, 16.times.16 picture elements as shown in FIG. 1A) and a motion vector indicates that a certain block the (objective block 11) has moved to another position on a second picture from which a difference is taken (as shown in FIG. 1B).
When a difference is taken between two frames after adjusting the second frame on the basis of a motion vector, the difference is minimized so that highly efficient coding can be performed. Conversely speaking, if the motion vector is obtained so that the difference between frames is minimized again highly efficient coding is made possible.
It is known to improve transmission efficiency of the motion vector, by using variable length coding of the motion vector. In particular, as shown in FIG. 2, picture data is supplied to a motion vector detecting circuit 10 which detects a motion vector, and the motion vector is then provided to a variable length coding circuit 20 and coded to provide a variable length coding code (VLC code).
Although the permissible range and degree of accuracy for the motion vector are theoretically unrestricted, and there are in fact practical limit such as hardware size, etc,. For example, consider the case in which variable length coding is to be performed the range of permissible range of the motion vector may be either .+-.7, picture elements or .+-.15 picture elements from the origin (i.e., the center), and the degree of accuracy may be 1 picture element unit or 0.5 picture element unit.
In this case two different variable length coding tables are needed for the 1 picture element degree of accuracy. That is, the table for the range of .+-.7 picture elements with 1 picture element accuracy has 15 elements 7, 6, . . . , 0, . . . , -6, -7, while the table for the range of .+-.15 picture elements with the same degree of accuracy has 31 elements 15, 14, . . . , 0, . . . , -14, -15. In addition, a table for the range of .+-.7 picture elements with 0.5 picture element which has 29 elements 7.0, 6.5, . . . , 0, . . . , -6.5, -7.0.
Accordingly, when there are plural kinds of motion vector ranges and there are plural degrees of accuracy, the number of tables that are needed increases, leading to more onerous hardware requirements.

Variable length coding apparatus and method for motion vector


Methane in a feedstock gas having methane as its main component, is partially oxidized with oxygen, which selectively permeates from a first side to a second side of a oxygen selective permeation ceramic membrane. Air is contacted with the first side of the oxygen selective permeation ceramic membrane, and the feedstock gas containing methane is contacted with the second side of the oxygen selective permeation ceramic membrane. A first catalyst for partial oxidation of methane is disposed two-dimensionally on the second side of the oxygen selective permeation ceramic membrane, and a second catalyst for partial oxidation of methane is disposed three-dimensionally in the feedstock gas stream downstream from the first catalyst. Furthermore, steam is mixed into the feedstock gas stream at a ratio of 0.25 to 0.5 moles of steam based on the moles of carbon in the feedstock gas.

Producing a clean synthetic liquid fuel from a gas including methane as a feedstock contributes to the effective utilization of untapped natural gas and other resources and to the supply of an environmentally-friendly clean energy source. Actually, however, technologies for producing synthesis liquid fuel have hardly been commercialized anywhere in the world at present, except for methanol that is used as the feedstock for the chemical industry. This is because the technology is not economically viable for commercial application based on the current level of technology and the prices of existing fuels, indicating that further improvement of the technology is indispensable for reducing the cost. This technology consists of two phases; the production of a synthesis gas from a gas that contains methane, and the production of a liquid fuel from the synthesis gas. Reduction of cost in the former phase that accounts for about 60% of the total equipment investment has a greater impact. With the background of concerns over shortage of natural resources and the global environment, there have been growing social demand for practical application of this technology, thus prompting the development of technologies that reduce the cost and improve the energy efficiency in the stage of producing the synthesis gas.
At present a steam reforming process is principally employed in the production of synthesis gas used as the feedstock for producing methanol or other purposes. In addition to the fact that steam reforming is an endothermic reaction that requires the supply of heat from the outside, an excessive quantity of steam is supplied in order to avoid a decrease in catalytic performance resulting from the precipitation of carbon as well as the carburizing metal dust in a waste heat recovery boiler installed downstream of the reactor, which result in a low energy efficiency and high investment cost. While a hydrogen to carbon monoxide ratio of 3 has been achieved for the synthesis gas produced by steam reforming, it would be necessary to add a large quantity of CO2 to the feedstock gas or partially separate hydrogen from the synthesis gas, in order to provide the synthesis gas that is suited for the production of liquid fuel, namely one that has the above-mentioned ratio of 2 or 1.
In order to overcome the drawbacks described above, especially the necessity to supply heat from the outside, there has been a progress in the development of internally heated reforming reactor technology that introduces pure oxygen directly into the gas flow which includes methane. According to this technology, the heat required for the reforming reaction is supplied from the combustion of the feedstock gas that takes place inside of the reactor, and is based on partial oxidation of methane that is represented by the following formula (standard enthalpy of formation is 298K).CH4+1/2O2→CO+2H2+35.5 kJ/molThis technology can be classified by the form of reaction into gas phase partial oxidation, fixed bed autothermal reforming, fluidized bed autothermal reforming and catalyst partial oxidation. Except for the catalyst partial oxidation that is said to have partial oxidation reaction proceed in a single stage, these processes include the methane combustion reaction and the reforming reaction of CO2, H2O that are generated by the combustion with methane. That is, the following exothermic reaction and endothermic reactions proceed in combination.CH4+2O2→CO2+2H2O+801.7 kJ/molCH4+H2O→CO+3H2−206 kJ/molCH4+CO2→2CO+2H2−247.5 kJ/molAmong these processes, the process that is being applied to commercial plants is the gas phase partial oxidation while there has not been much progress in the commercial application of the fixed bed autothermal reforming process. The fluidized bed autothermal reforming process remains at the stage of pilot testing, while the catalytic partial oxidation remains at the basic research stage. As these technologies utilize the thermal energy supplied from the inside, energy efficiency is improved over that of the steam reforming, but it is difficult to significantly reduce the cost because it requires the supply of expensive pure oxygen produced by the cryogenic distillation air separator.
Current technologies to produce oxygen, represented by the cryogenic distillation, are capital intensive and energy intensive, and have low prospect of significant cost reduction because they are intrinsically based on the difference in the boiling point of oxygen and nitrogen that have very low boiling points, in spite of some advancements that have been made so far including the improvement in the process configuration. With this background, a novel technology for producing oxygen that has been vigorously researched in Western countries in recent years is the high temperature (up to 850° C.) oxygen separation technology that uses a dense mixed conductivity ceramic membrane. This technology is regarded as very promising because it employs a compact facility and offers the possibility of reducing energy consumption. In a mixed conductivity ceramic membrane, oxygen molecules included in air are selectively ionized on the surface of the membrane and pass through the crystal lattice, being driven by the difference in partial pressure of oxygen on both sides of the membrane. At the same time, electrons move in a direction opposite to the flow of oxygen ions so as to maintain the electrical neutrality Partial pressure of oxygen on the methane side can be minimized by placing a catalyst on the side opposite to the air side so as to oxidize methane and other substances (consume oxygen), thereby maximizing the difference in partial pressure of oxygen, namely the driving force for the selective permeation of oxygen. As the ceramic material exhibits mixed conductivity at a high temperature from 800 to 900° C., partial oxidation reaction of methane and other substances can be carried out simultaneously with the separation of air, namely in a single unit, thus providing the possibility that the reactor could become more compact and low-cost. For these reasons, basic research on the use of the ceramic membrane has been conducted by many researchers, such as the methane oxidation coupling and production of synthesis gas from methane. Particularly intensive efforts have been poured, world-wide, into the production of synthesis gas from methane including a big research project with a fund granted by the U.S. Energy Department, since there are possibilities of drastic cost reduction and reducing energy consumption.
As the basic technologies upon which the synthesis gas producing technologies that employ a ceramic membrane reactor to produce synthesis gas from a methane-containing gas have been developed, materials for the mixed conductivity ceramic membrane, configuration of the membrane including thin membrane, methane reforming catalyst and the arrangement thereof, configuration of the reactor including the sealing method, reaction heat supplying method and the entire process including the membrane reactor have been disclosed.
For the properties of the mixed conductivity ceramic membrane material, material stability as well as high oxygen permeability, particularly stability of the crystal structure in the reducing atmosphere are of great importance. When a change in the crystal structure and/or the phase change occurs, the membrane often swells and this eventually results in the destruction of the ceramic membrane. Progress has already been made, world-wide, for the development of ceramic membrane materials that have high oxygen permeability and high material stability in the reducing atmosphere, such as Sr1.7La0.3Ga0.6Fe1.4O5.15 (WO99/21649) that has very high level of oxygen permeability and material stability in the reducing atmosphere.
As for the configuration of the membrane, it must be thin in order to increase the oxygen permeability against the bulk diffusion resistance of oxygen in the ceramic membrane, and such proposals have been made as a method for producing an inorganic thin film by means of organometallic chemical deposition on a porous supporting structure (Japanese Unexamined Patent Publication (Kokai) No. 6-135703). Also in case the surface exchange such as selective dissociation of oxygen reaches the rate-determining step of the oxygen permeation rate as the membrane is made thinner, it may be required to add a porous layer that increases the surface area or add an oxygen dissociating catalyst (WO98/41394, etc.).
As for the overall process that contains the membrane reactor for producing the synthesis gas from a gas including methane, proposals have been made on such aspects as the form of a process with various unit operations specified, and process running conditions that take the composition of feed gas into consideration (EP-0882670A1, EP-0926097A1).
For the reactor used for producing the synthesis gas from a gas that contains methane using a ceramic membrane, proposals have been disclosed as concepts of the reactor including the materials (U.S. Pat. No. 5,306,411, WO98/48921, WO99/21640, WO99/21649, EP-0962422A1, EP-0962423A1, U.S. Pat. No. 6,033,632), a method for supplying thermal energy for the reforming of hydrocarbon (WO98/48921), methods for controlling the reaction temperature for partial oxidation of hydrocarbon that is an exothermal reaction (Japanese Unexamined Patent Publication (Kokai) No. 11-70314, U.S. Pat. No. 6,010,614) and a method for sealing the joint between the ceramic membrane and metal (U.S. Pat. No. 5,725,218).
In a membrane reactor wherein synthesis gas is produced, oxygen flows along the flow of gas that contains methane thereby to join there with and, therefore methane concentration tends to be high especially in the upstream thus making carbon precipitation more likely to occur. This takes place in a reaction represented by the following formula.CH4→C+2H2Since the process of producing clean liquid fuel such as Fischer-Tropsch synthesis oil, methanol or dimethyl ether requires the operating pressure of 30 atm or higher, and pressure of the gas including natural gas such as methane must be as high as 50 atm or higher, the operating pressure of the synthesis gas production process is required to be at least 20 atm or higher, that means far higher probability of carbon precipitation than in the case of normal pressure. While the invention of WO99/21649 discloses two-dimensional and three-dimensional arrangements of various methane reforming catalysts, it does not disclose any specific means of suppressing the precipitation of carbon under normal to high pressures. While the invention of EP-0999180A2 discloses a method for suppressing carbon precipitation by recycling the product from the membrane reactor, consisting mainly of hydrogen, to the feed side, it has a drawback of complex process. Meanwhile, it is known that a methane partial oxidation catalyst such as those based on Ni loses the methane reforming capability due to oxidation. As oxygen comes out of the membrane in the membrane reactor, the methane reforming catalyst located near the surface of the membrane tends to be deactivated by oxidation. On the other hand, an increase in partial pressure of oxygen, on the gas side where methane is included that is generated due to decelerated progress of the methane reforming reaction, leads to a significant decrease in the amount of oxygen permeable through the ceramic membrane. In order to put the membrane reactor in commercial applications for producing synthesis gas, it is necessary to provide specific means for solving these problems without compromising the most remarkable feature of the reactor, namely the reactor and related facility can be made compact. However, no basic technologies related to the reaction have been disclosed as to the methane partial oxidation catalyst and the arrangement thereof that would enable practical application, in spite of various technologies related to the reactor that have been proposed so far.
The present invention relates to an oxygen permeation membrane reactor for producing synthesis gas using a gas that contains methane and air as the feedstock, and provides a method for producing synthesis gas with high efficiency, stability and low cost in a range from normal pressure to high pressure around 20 atm, while overcoming such drawbacks as carbon precipitation on the catalyst and deactivation of catalyst due to oxidation of a metal catalyst, and also providing solutions to problems caused by these drawbacks such as a decrease in oxygen supply from the ceramic membrane and the consumption of catalyst.

Method for partial oxidation of methane using dense, oxygen selective permeation ceramic membrane


An electronic device includes an earphone port, an audio amplifier, a digital processor, a multi-way selection switch, and an earphone detection response circuit. The earphone port includes left and right channel pins. The audio amplifier includes an earphone left channel output pin and an earphone right channel output pin. The digital processor includes a data transmission pin and a data receive pin. The multi-way selection switch includes four switches electrically connected between the data transmitting pin and the left channel pin, the data receive pin and the right channel pin, the earphone left channel output pin and the left channel pin, and the earphone right channel output pin and the right channel pin, respectively. The earphone detection response circuit turns on a first switch and a second switch, and turns off a third switch and a fourth switch when the earphone port does not receive an earphone.

Electronic devices, such as mobile phones and tablet computers, often need to be debugged when software of the electronic device is updated or broken. However, a debug port used to debug the electronic device is often covered by a casing of the electronic device, so the casing needs to be opened to debug the electronic device, which is inconvenient.

Electronic device capable of being debugged via earphone port

ShenZhen Goldsun Network Intelligence Technology Co., Ltd.


The broadening of the lines in NRF from an isotope that is part of a material may be due to several causes: the temperature of the material, the molecular structure of the material and the crystalline structure of the material. By measuring the broadening caused by the molecular structure and the crystalline structure the material itself can be identified. The exact energy of the lines in NRF may also depend on the nature of the crystalline and molecular structure of the material. By measuring the changes in the energy of the NRF lines caused by the structure of the material the material itself may be identified. These techniques provide a “fingerprint” of the molecule or crystal that is involved. The fingerprint information may be used to determine a potential threat.

Nuclear Resonance Fluorescence results when a nucleus is excited by photon absorption and then subsequently decays via photon emission to lower lying states of that nucleus. The decay is often but not always to the ground state. The emitted photon energy that results from a decay may be characteristic of the specific isotope which has decayed and therefore the detection of a photon of that energy may allow the identification of the presence of that isotope.
Because the emitted photon energies in NRF are in the MeV region, the photons involved may be very penetrating. This may allow NRF to be used for the non-intrusive inspection of dense cargo or materials. See U.S. Pat. No. 5,115,459, Explosives Detection Using Resonance Fluorescence of Bremsstrahlung Radiation, U.S. Pat. No. 5,420,905, Detection of Explosives and Other Materials Using Resonance Fluorescence, Resonance Absorption, and Other Electromagnetic Processes with Bremsstrahlung Radiation, and U.S. Pat. No. 7,120,226, Adaptive Scanning Of Materials Using Nuclear Resonance Fluorescence Imaging, the contents of all of which are hereby incorporated by reference.
The energies of the photons that are resonant with a specific isotope are for the most part determined by the nuclear structure of that isotope, and the nature of the strong nuclear interactions that bind that nucleus. Small effects may arise, however, from the recoil of the nuclear isotope due to the conservation of energy and momentum upon photon absorption and emission.
In particular, when a nuclear isotope absorbs a photon the energy of the absorbed resonant photon may not be simply the energy difference between the ground state of the nucleus and the resulting excited state of the nucleus. The photon energy must also account for the energy of excitation of the molecule or crystal to which the nucleus is bound. In a molecular structure, the molecule is generally excited because of the violent recoil of the nucleus caused by the conservation of momentum upon photon absorption. For light and heavy nuclei this recoil may be sufficient not just to excite the molecule but also to break the molecular bond. For crystalline materials, the recoil of the nuclear isotope may excite vibrations of the crystal in one or several of its many normal modes. The recoil may also break the nuclear isotope from its lattice position causing it to recoil almost freely through the crystal.

Methods and apparatus for the identification of molecular and crystalline materials by the doppler broadening of nuclear states bound in molecules, crystals and mixtures using nuclear resonance fluorescence


A boiler system is provided comprising: a furnace adapted to receive a fuel to be burned to generate hot working gases; a fuel supply structure associated with the furnace for supplying fuel to the furnace; a superheater section associated with the furnace and positioned to receive energy in the form of heat from the hot working gases; and a controller. The superheater section may comprise a platen including a tube structure with an end portion and a temperature sensor for measuring the temperature of the tube structure end portion and generating a signal indicative of the temperature of the tube structure end portion. The controller may be coupled to the temperature sensor for receiving and monitoring the signal from the sensor.

In a paper-making process, chemical pulping yields, as a by-product, black liquor, which contains almost all of the inorganic cooking chemicals along with lignin and other organic matter separated from the wood during pulping in a digester. The black liquor is burned in a recovery boiler. The two main functions of the recovery boiler are to recover the inorganic cooking chemicals used in the pulping process and to make use of the chemical energy in the organic portion of the black liquor to generate steam for a paper mill.
In a kraft recovery boiler, a superheater structure is placed in the furnace in order to extract heat by radiation and convection from the furnace gases. Saturated steam enters the superheater section, and superheated steam exits from the section. The superheater structure comprises a plurality of platens.

Boiler system controlling fuel to a furnace based on temperature of a structure in a superheater section


This invention relates to a sealed container containing a powder formulation comprising a dehydroepiandrosterone, its analogue(s) or salt(s) by itself or with a pharmaceutically or veterinarily acceptable carrier or diluent, and having a particle size of about 0.1 μm to about 100 μm. The formulation can be used to treat or prevent asthma, chronic obstructive pulmonary disease, lung inflammation, and other respiratory diseases or conditions. The formulation may be prepared by jet milling, and may be delivered through the respiratory tract or other routes using a nebulizer. The sealed container is provided in a device and/or a therapeutic kit.

1. Field of the Invention
This invention relates to a respirable dry powder formulation comprising a pharmaceutically or veterinarily acceptable carrier and a dehydroepiandrosterone (DHEA), DHEA derivative, or pharmaceutically or veterinarily acceptable salt thereof, sealed in a nebulizable form. Methods for preparation and delivering of the dry powdered formulation, and for treating asthma, chronic obstructive pulmonary disease (COPD), or other respiratory disease or condition, including microbial (including bacteria) or viral caused respiratory disease, such as severe acute respiratory syndrome (SARS). The formulation is provided in the form of a kit.
2. Description of the Background
Asthma and COPD and other respiratory ailments, associated with a variety of diseases and conditions, are extremely common in the general population, and more so in certain ethnic groups, such as African Americans. Respiratory ailments include microbial infections or viral infections (such as SARS). In many cases they are accompanied by inflammation, which aggravates the condition of the lungs. Asthma, for example, is one of the most common diseases in industrialized countries. In the United States it accounts for about 1% of all health care costs. An alarming increase in both the prevalence and mortality of asthma over the past decade has been reported, and asthma is predicted to be the preeminent occupational lung disease in the next decade. While the increasing mortality of asthma in industrialized countries could be attributable to the reliance upon beta agonists in the treatment of this disease, the underlying causes of asthma remain poorly understood.
Asthma is a condition characterized by variable, in many instances reversible obstruction of the airways. This process is associated with lung inflammation and in some cases lung allergies. Many patients have acute episodes referred to as "asthma attacks," while others are afflicted with a chronic condition. The asthmatic process is believed to be triggered in some cases by inhalation of antigens by hypersensitive subjects. This condition is generally referred to as "extrinsic asthma." Other asthmatics have an intrinsic predisposition to the condition, which is thus referred to as "intrinsic asthma," and may be comprised of conditions of different origin, including those mediated by the adenosine receptor(s), allergic conditions mediated by an immune IgE-mediated response, and others. All asthmas have a group of symptoms, which are characteristic of this condition: bronchoconstriction, lung inflammation and decreased lung surfactant. Existing bronchodilators and anti-inflammatories are currently commercially available and are prescribed for the treatment of asthma. The most common anti-inflammatories, corticosteroids, have considerable side effects but are commonly prescribed nevertheless. Most of the drugs available for the treatment of asthma are, more importantly, barely effective in a small number of patients.
Chronic obstructive pulmonary disease (COPD) causes a continuing obstruction of airflow in the airways. COPD is characterized by airflow obstruction that is generally caused by chronic bronchitis, emphysema, or both. Commonly, the airway obstruction is mostly irreversible. In chronic bronchitis, airway obstruction results from chronic and excessive secretion of abnormal airway mucus, inflammation, bronchospasm, and infection. Chronic bronchitis is also characterized by chronic cough, mucus production, or both, for at least three months in at least two successive years where other causes of chronic cough have been excluded. In emphysema, a structural element (elastin) in the terminal bronchioles is destroyed leading to the collapse of the airway walls and inability to exhale "stale" air. In emphysema there is permanent destruction of the alveoli. Emphysema is characterized by abnormal permanent enlargement of the air spaces distal to the terminal bronchioles, accompanied by destruction of their walls and without obvious fibrosis. COPD can also give rise to secondary pulmonary hypertension. Secondary pulmonary hypertension itself is a disorder in which blood pressure in the pulmonary arteries is abnormally high. In severe cases, the right side of the heart must work harder than usual to pump blood against the high pressure. If this continues for a long period, the right heart enlarges and functions poorly, and fluid collects in the ankles (edema) and belly. Eventually the left heart begins to fail. Heart failure caused by pulmonary disease is called cor pulmonale.
COPD characteristically affects middle aged and elderly people, and is one of the leading causes of morbidity and mortality worldwide. In the United States it affects about 14 million people and is the fourth leading cause of death, and the third leading cause for disability in the United States. Both morbidity and mortality, however, are rising. The estimated prevalence of this disease in the United States has risen by 41% since 1982, and age adjusted death rates rose by 71% between 1966 and 1985. This contrasts with the decline over the same period in age-adjusted mortality from all causes (which fell by 22%), and from cardiovascular diseases (which fell by 45%). In 1998 COPD accounted for 112,584 deaths in the United States.
COPD, however, is preventable, since it is believed that its main cause is exposure to cigarette smoke. Long-term smoking is the most frequent cause of COPD. It accounts for 80 to 90% of all cases. A smoker is 10 times more likely than a non-smoker to die of COPD. The disease is rare in lifetime non-smokers, in whom exposure to environmental tobacco smoke will explain at least some of the airways obstruction. Other proposed etiological factors include airway hyper responsiveness or hypersensitivity, ambient air pollution, and allergy. The airflow obstruction in COPD is usually progressive in people who continue to smoke. This results in early disability and shortened survival time. Stopping smoking reverts the decline in lung function to values for non-smokers. Other risk factors include: heredity, second-hand smoke, exposure to air pollution at work and in the environment, and a history of childhood respiratory infections. The symptoms of COPD include: chronic coughing, chest tightness, shortness of breath, an increased effort to breathe, increased mucus production, and frequent clearing of the throat.
There is very little currently available to alleviate symptoms of COPD, prevent exacerbations, preserve optimal lung function, and improve daily living activities and quality of life. Many patients will use medication chronically for the rest of their lives, with the need for increased doses and additional drugs during exacerbations. Medications that are currently prescribed for COPD patients include: fast-acting β2-agonists, anticholinergic bronchodilators, long-acting bronchodilators, antibiotics, and expectorants. Amongst the currently available treatments for COPD, short term benefits, but not long term effects, were found on its progression, from administration of anti-cholinergic drugs, β2 adrenergic agonists, and oral steroids.
Short and long acting inhaled β2 adrenergic agonists achieve short-term bronchodilation and provide some symptomatic relief in COPD patients, but show no meaningful maintenance effect on the progression of the disease. Short acting β2 adrenergic agonists improve symptoms in subjects with COPD, such as increasing exercise capacity and produce some degree of bronchodilation, and even an increase in lung function in some severe cases. The maximum effectiveness of the newer long acting inhaled, β2 adrenergic agonists was found to be comparable to that of short acting β2 adrenergic agonists. Salmeterol was found to improve symptoms and quality of life, although only producing modest or no change in lung function. In asthmatics, however, β2 adrenergic agonists have been linked to an increased risk of death, worsened control of asthma, and deterioration in lung function. β2-agonists, such as albuterol, help to open narrowed airways. The use of β2-agonists can produce paradoxical bronchospasm, which may be life threatening to the COPD patient. In addition, the use of β2-agonists can produce cardiovascular effects, such as altered pulse rate, blood pressure and electrocardiogram results. In rare cases, the use of β2-agonists can produce hypersensitivity reactions, such as urticaria, angioedema, rash and oropharyngeal edema. In these cases, the use of the β2-agonist should be discontinued. Continuous treatment of asthmatic and COPD patients with the bronchodilators ipratropium bromide or fenoterol resulted in a faster decline in lung function, when compared with treatment provided on a need basis, therefore indicating that they are not suitable for maintenance treatment. The most common immediate adverse effect of β2 adrenergic agonists, on the other hand, is tremors, which at high doses may cause a fall in plasma potassium, dysrhythmias, and reduced arterial oxygen tension. The combination of a β2 adrenergic agonist with an anti-cholinergic drug provides little additional bronchodilation compared with either drug alone. The addition of ipratropium to a standard dose of inhaled β2 adrenergic agonists for about 90 days, however, produces some improvement in stable COPD patients over either drug alone. Anti-cholinergic agents were found to produce greater bronchodilation in combination with anti-cholinergic agents than β2 adrenergic agonists, in people with COPD. Overall, the occurrence of adverse effects with β2 adrenergic agonists, such as tremor and dysrhythmias, is more frequent than with anti-cholinergics. Thus, neither anti-cholinergic drugs nor β2 adrenergic agonists have an effect on all people with COPD; nor do the two agents combined.
Anti-cholinergic drugs achieve short-term bronchodilation and produce some symptom relief in people with COPD, but no improved long-term prognosis even with inhaled products. Most COPD patients have at least some measure of airways obstruction that is somewhat alleviated by ipratropium bromide. "The lung health study" found in men and women smokers spirometric signs of early COPD. Three treatments compared over a five year period found that ipratropium bromide had no significant effect on the decline in the functional effective volume of the patient's lungs whereas smoking cessation produced a slowing of the decline in the functional effective volume of the lungs. Ipratropium bromide, however, produced serious adverse effects, such as cardiac symptoms, hypertension, skin rashes, and urinary retention. Anticholinergic bronchodilators, such as ipratropium bromide, and theophylline derivatives, help to open narrowed airways. Long-acting bronchodilators help to relieve constriction of the airways and help prevent bronchospasm associated with COPD. Theophyllines have a small bronchodilatory effect in COPD patients whereas they have some common adverse effects, and they have a small therapeutic range given that blood concentrations of 15-20 mg/l are required for optimal effects. Adverse effects include nausea, diarrhea, headache, irritability, seizures, and cardiac arrhythmias, and they occur at highly variable blood concentrations and, in many people, they occur within the therapeutic range. The theophyllines' doses must be adjusted individually according to smoking habits, infection, and other treatments, which is cumbersome. Although theophyllines have been claimed to have an anti-inflammatory effect in asthma, especially at lower doses, none has been reported in COPD, although their bronchodilating short-term effect appears to be statistically different from placebo. The adverse effects of theophyllines and the need for frequent monitoring limit their usefulness. There is no evidence that anti-cholinergic agents affect the decline in lung function, and mucolytics have been shown to reduce the frequency of exacerbations but with a possible deleterious effect on lung function. The long-term effects of β2 adrenergic agonists, oral corticosteroids, and antibiotics have not yet been evaluated, and up to the present time no other drug has been shown to affect the progression of the disease or survival.
Oral corticosteroids elicit some improvement in baseline functional effective volume in stable COPD patients whereas systemic corticosteroids have been found to be harmful at least producing some osteoporosis and inducing overt diabetes. The longer term administration of oral corticosteroids may be useful in COPD, but their usefulness must be weighed against their substantial adverse effects. Inhaled corticosteroids have been found to have no real short-term effect on airway hyper-responsiveness to histamine, but a small long-term effect on lung function, e.g., in pre-bronchodilator functional effective volume. Fluticasone treatment of COPD patients showed a significant reduction in moderate and severe (but not mild) exacerbations, and a small but significant improvement in lung function and six minute walking distance. Oral prednisolone, inhaled beclomethasone or both had no effects in COPD patients, but lung function improved oral corticosteroids. Mucolytics have a modest beneficial effect on the frequency and duration of exacerbations but an adverse effect on lung function. Neither N-acetylcysteine nor other mucolytics, however, have a significant effect in people with severe COPD (functional effective volume<50%) in spite of evidencing greater reductions in frequency of exacerbation. N-acetylcysteine produced gastrointestinal side effect. Long-term oxygen therapy administered to hypoxaemic COPD and congestive cardiac failure, patients, had little effect on their rates of death for the first 500 days or so, but survival rates in men increased afterwards and remained constant over the next five years. In women, however, oxygen decreased the rates of death throughout the study. Continuous oxygen treatment of hypoxemic COPD patients (functional effective volume<70% predicted) for 19.3 years decreased overall risk of death. To date, however, only life style changes, smoking cessation and long term treatment with oxygen (in hypoxaemics), have been found to alter the long-term course of COPD.
Antibiotics are also often given at the first sign of a respiratory infection to prevent further damage and infection in diseased lungs. Expectorants help loosen and expel mucus secretions from the airways, and may help make breathing easier.
In addition, other medications may be prescribed to manage conditions associated with COPD. These may include: diuretics (which are given as therapy to avoid excess water retention associated right-heart failure), digitalis (which strengthens the force of the heartbeat), painkillers cough suppressants, and sleeping pills. This latter list of medications help alleviate symptoms associated with COPD but do not treat COPD.
Thus, there is very little currently available to alleviate symptoms of COPD, prevent exacerbations, preserve optimal lung function, and improve daily living activities and quality of life.
Severe acute respiratory syndrome (SARS) is a respiratory illness that has recently been reported in Asia, North America, and Europe. In general, SARS patients initial experience a fever of greater than 100.4° F. (>38.0° C.). This may be accompanied or followed by headache, an overall feeling of discomfort, and body aches. Certain patients also experience respiratory symptoms. Following 2 to 7 days, SARS patients may also develop a dry cough and experience breathing trouble. SARS appears to spread primarily by close person-to-person contact. The majority of SARS patients appear to have been involved people who cared for or lived with others with SARS, or had direct contact with an infectious material (e.g., respiratory secretions) from another patient with SARS. Potential ways in which SARS can be spread include touching the skin of other people or objects that are contaminated with infectious droplets and then touching your eye(s), nose, or mouth. This can happen when someone who is sick with SARS coughs or sneezes droplets onto themselves, other people, or nearby surfaces.
Scientists at the Centers for Disease Control and Prevention (CDC) and other laboratories have detected a previously unrecognized coronavirus in patients with SARS: SARS-CoV, which is the leading hypothesis for the cause of SARS The sequence of SARS-CoV has been sequenced and all of the sequence, except for the leader sequence, was derived directly from viral RNA. The genome of the SARS coronavirus is 29,727 nucleotides in length and the genome organization is similar to that of other coronaviruses. Open reading frames have been identified that correspond to the predicted polymerase protein (polymerase 1a, 1b), spike protein (S), small membrane protein (E), membrane protein (M) and nucleocapsid protein (N)
Researchers worldwide are been working frantically to develop a treatment for SARS. Currently no treatment has been found to be effective at stopping the SARS-CoV coronavirus associated with SARS. The antiviral drugs currently used, or considered, for treating SARS include ribavirin, 6-azauridine, pyrazofurin, mycophenolic acid, and glycyrrhizin. However, all these drugs have serious side effects (e.g., side effects of glycyrrhizin include raised blood pressure and lowered potassium levels). Treatment with the anti-inflammatory drug methylprednisolone has been shown achieve some improvement in SARS patients (So, L. K., et al., "Development of a standard treatment protocol for severe acute respiratory syndrome", Lancet 361(9369): 1615-7, 2003).
Dehydroepiandrosterones are non-glucocorticoid steroids. DHEA, also known as 5androsten-3 beta-ol-17-one and DHEA sulfate (DHEA-S), a sulfated form of DHEA, are endogenous hormones secreted by the adrenal cortex in primates and a few non-primate species in response to the release of ACTH. DHEA is a precursor of both androgen and estrogen steroid hormones important in several endocrine processes. Current medical use of DHEA is limited to controlled clinical trials, and as a food supplement, and is thought to have a role in levels of DHEA in the central nerve system (CNS), and in psychiatric, endocrine, gynecologic, obstetric, immune, and cardiovascular functions.
DHEA-S or its pharmaceutically acceptable salts are believed to improve uterine cervix maturation and uterine musculature sensitivity to oxytocin in late phase pregnancy. DHEA-S and its pharmaceutically acceptable salts are thought to be effective in the therapy for dementia, for the therapy of hyperlipemia, osteoporosis, ulcers, and for disorders associated with high levels of, or high sensitivity to adenosine, such as steroid-dependent asthma, and other respiratory and lung diseases. Dehydroepiandrosterone itself was administered intravenously previously, subcutaneously, percutaneously, vaginally, topically and orally in clinical trials. In preformulation studies, however, the anhydrous form of DHEA sodium sulfate (DHEA-SNa) was found to be unstable to humidity, and its dihydrate form (DHEA-SNa) was found to be more stable under conditions of normal humidity.
As is known, various operations may be performed on medicinal agents during pharmaceutical processing that often affect the physicochemical properties and stability of the compounds. Prolonged grinding of the dehydroepiandrosterone sodium sulfate dihydrate produced a decrease in crystallinity and loss of hydration water; the latter decreasing storage stability and producing DHEA, its degradation product.
Accordingly, there is a need for a powder formulation of dehydroepiandrosterone compounds, their analogues and salts, that will show good dispersibility and shelf stability, as well as appropriate respirable properties. Such formulation would make it possible to deliver the dehydroepiandrosterone compounds, analogues and salts in a highly efficacious and cost effective manner.
U.S. Pat. No. 5,527,789 discloses a method of combating cancer in a subject by administering to the subject dehydroepiandrosterone (DHEA) or DHEA-related compound, and ubiquinone to combat heart failure induced by the DHEA or DHEA-related compound.
U.S. Pat. No. 6,087,351 discloses an in vivo method of reducing or depleting adenosine in a subject's tissue by administering to the subject dehydroepiandrosterone (DHEA) or DHEA-related compound. U.S. Pat. No. 6,087,351 discloses that solid particulate compositions containing respirable dry particles of micronized active compound may be prepared by grinding dry active compound with a mortar and pestle, and then passing the micronized composition through a 400 mesh screen to break up or separate out large agglomerates. Also, a solid particulate composition comprised of the active compound may optionally contain a dispersant which serves to facilitate the formation of an aerosol; and a suitable dispersant is lactose, which may be blended with the active compound in any suitable ratio (e.g., a 1 to 1 ratio by weight).
DHEA and DHEA-S have been described to treat COPD (U.S. patent application Ser. No. 10/454,061, filed Jun. 3, 2003, and International Application No. PCT/US02/12555, filed Apr. 21, 2002, published Oct. 31, 2002).

Nebulizer formulations of dehydroepiandrosterone and methods of treating asthma or chronic obstructive pulmonary disease using compositions thereof