A diffuser assembly for diffusing a fluid from a fluid source into a medium to aerate the medium. The diffuser assembly including a diffuser body in fluid communication with the fluid source and a membrane connected to the diffuser body. The membrane is circular and includes a slitting pattern divided into a series of similar angular segments. The segments are positioned adjacent each other in a circular arrangement to substantially cover the membrane. Each segment includes a plurality of rows each having a plurality of slits. The slits within the segment are arranged in a parallelogram pattern. A first line extending between adjacent slits in a common row is substantially the same length as a second line extending between adjacent slits in adjacent rows.

The present invention relates to aeration diffusers used in wastewater treatment tanks, and more specifically to the piercing pattern on the elastomeric membranes of the diffuser assemblies.
Aeration systems are used in wastewater treatment tanks to introduce oxygen into the wastewater. The wastewater is typically contained in treatment tanks, and air is forced through diffuser assemblies to produce fine bubbles that flow through the wastewater. Diffusing a high volume of air or oxygen into the wastewater in the form of fine bubbles facilitates biological growth during the waste treatment process. Supplying air into the treatment tank also serves to prevent sedimentation of the wastewater within the treatment tank. The treatment tank usually includes a network of air distribution piping for transferring air to the diffuser assemblies. The network of air distribution piping typically includes a drop pipe extending from an air supply to a manifold that is submerged within the wastewater. The submerged manifold is connected to a plurality of submerged distribution pipes that are also submerged within the wastewater and generally arranged in a parallel configuration along the bottom of the treatment tank when such tank is of rectangular design. Each distribution pipe typically supports a number of diffuser assemblies such that the diffuser assemblies are also submerged within the wastewater along the bottom of the tank.
Each diffuser assembly includes a diffuser body and includes a membrane coupled to the diffuser body. The membrane includes a perforation pattern that generates the fine bubbles. Diffuser assemblies can include circular or rectangular diffuser bodies and include corresponding circular or rectangular membranes. Many different types of membranes are known and are described in detail below.
The perforation pattern of circular membranes can be either segmented or unsegmented. Segmented patterns divide the surface area of the circular membrane into a number of equal-sized, pie-shaped segments. Each of the segments includes the same or substantially the same piercing pattern. Segmentation allows consistent spacing between and across rows regardless of the radial distance from the center of the membrane. Some known segmented patterns include square or rectangular piercing patterns while others include parallelogram piercing patterns. As shown in FIG. 1, the square or rectangular piercing pattern is generated by creating slits in a square or rectangular pattern across the segment. The parallelogram piercing pattern is generated by creating punctures in a parallelogram pattern across the segment. Slitting is different from puncturing in that a slit is an extended cut into the membrane and a puncture is a generally circular hole through the membrane. Some square or rectangular patterns use curved slits and orient the curved slits in opposite facing directions in adjacent rows.
With further reference to FIG. 1a, the line b extending between midpoints of adjacent slits in a common row is the same length as the line a extending between midpoints of adjacent slits of adjacent rows. Specifically, the lines a, b extend between common points (e.g., center points) of the slits. Also, the angle A defined between the lines a, b equals 90 degrees. The common length and 90 degree angle define the square pattern. A rectangular pattern is defined when the 90 degree angle exists, but the lines a, b are not equal. In one embodiment, the perpendicular distance d between adjacent rows is 0.100 inches and the lines a, b are also 0.100 inches. This allows for a maximum bubble diameter D of up to 0.100 inches, at which diameter adjacent bubbles touch and likely coalesce into a single larger bubble which transfers oxygen less effectively than two smaller uncoalesced bubbles.
On round membrane diffusers, unsegmented patterns do not divide the piercing pattern into repeatable angular segments. Known types of unsegmented patterns include a circumferential slitting pattern, a spiral slitting pattern, and a random puncturing pattern. The circumferential slitting pattern includes rows of slits spaced at radial intervals across the surface area of the circular membrane. The relative spacing between adjacent slits is not consistent and varies depending upon the location of the slit on the membrane. The spiral slitting pattern is similar except that it includes a single row of slits that gradually increases its radial position around the circular membrane such that the row wraps or spirals around itself. The random puncturing pattern does not include any repeatable pattern and therefore there is no consistent spacing in any direction between adjacent punctures. To accommodate a maximum bubble size of 0.100 inches before coalescence, such random patterns must accommodate the closest adjacent slits, and are forced to use a row-to-row spacing of 0.100 inches. This pattern is inefficient in the sense that over most of the membrane the center-to-center distance between adjacent slits is greater than 0.100 inches.
Rectangular membranes are generally unsegmented and include a piercing pattern that is continuous across the surface area of the membrane. Some examples of piercing patterns for rectangular membranes include diamond, parallelogram, square or rectangular slitting patterns. With reference to FIG. 1A, a diamond pattern is defined when the base angle A is 60 degrees and the lines a, b are the same distance. In contrast, a parallelogram has a base angle greater than or less than 60 degrees and lines a, b are not equal distances.

Aeration diffuser membrane slitting pattern

Siemens Water Technologies Holding Corp.


A device for fixing a segment of tubing in the form of a loop, for an apparatus by which a fluid is fed to or out from a patient via tubing, in particular for monitoring vascular access in extra-corporeal blood treatment, and a tubing and an arrangement for monitoring, each having the device for fixing the segment, are also described. The fixing of the segment includes a guiding piece and a securing piece. The guiding piece fixes intersecting portions of the segment which forms an eye, thereby forming a loop which contracts under a tractive stress. The securing piece fixes a portion of the segment forming the eye such that when the loop tightens, that portion of the segment does not slip through the guiding piece. Alternatively, intersecting portions of the segment are fixed in a loop only by a guiding piece formed as an annular body.

In the field of medical technology, there are a large number of known pieces of apparatus by which, via tubing, fluids can be fed to a patient or fluids can be fed out of the patient. Access is generally gained to the patient in this case by means of a catheter for introduction into organs of the body or by means of a canula or needle for puncturing vessels. It has to be ensured that there is proper access to the patient during examination or treatment. It is therefore necessary for the access to the patient to be monitored.
An application which makes particularly severe demands on the safety of the access to the vessel is extra-corporeal blood treatment in which blood is fed out of the patient via arterial tubing which has an arterial puncturing canula, the blood is conveyed through a dialyser, and is fed back to the patient via venous tubing which has a venous puncturing canula. Even though the access to the patient is regularly monitored by the hospital staff, there is basically a danger in this case of the venous puncturing canula slipping out of the patient's blood vessel unnoticed. Whereas if the arterial canula slips out this involves air being drawn into the arterial tubing, which results in a visual and/or optical alarm being given due to the detection of air by the machine and in the treatment being interrupted, the slipping-out of the venous canula, and the free flow of blood into the surroundings of which there is then a danger, cannot readily be detected. However, if the slipping-out of the venous canula is not detected immediately, the patient may exsanguinate.
There are a large number of different arrangements in the prior art for solving this problem. Some of these arrangements have recourse to safety arrangements which are present as standard in the blood treatment machines and cause an immediate interruption of the extra-corporeal circulation of blood if there is a vascular access which is not in a proper state. The safety arrangements which are present as standard in treatment machines are generally based on monitoring the pressure in the extra-corporeal blood circuit. However, it has been found in practice that the slipping-out particularly of the venous puncturing canula cannot be detected with sufficient reliability simply by monitoring the pressure in the extra-corporeal blood circuit. It is true that some known safety arrangements do have adequate sensitivity but they also react very sensitively to changes in the patient's position, which often results in false alarms. It is also a disadvantage that existing pieces of blood treatment apparatus cannot readily be retrofitted with the known monitoring arrangements and instead the retrofitting calls for a complicated and cost-intensive incursion to be made into the treatment apparatus.
International Patent Publication No. WO 2007/104350 A1 describes an easily operated arrangement which can be produced inexpensively and retrofitted at any time and which allows an access to a patient to be monitored safely and reliably. The monitoring of the access to the patient is based on the forming of a loop in the fluid-carrying tubing. It is assumed that slipping-out of the puncturing canula or the catheter is attributable to tractive forces being applied to the tubing. When the tubing is stressed in traction, the loop is necessarily pulled closed. This results in an increased pressure drop in the tubing and this is easy to detect.
Special fixing means are used to fix the tubing in the form of a loop. International Patent Publication No. WO 2007/104350 A1 describes two alternative embodiments which differ in that in one embodiment the fixing means are fixing pieces which are included loose with the tubing whereas in the other embodiment the fixing pieces are an integral part of the catheter for accessing the patient. The characteristic feature of the fixing pieces which are included loose is two eyes which are each used to receive a section of the tubing, the tubing being fixed in the form of a loop.
With the known fixing pieces, a section of the tubing can be fixed in the form of a loop which contracts under a tractive stress. It is a disadvantage however that the tractive force required for this is relatively high.

Device and method for fixing a segment of tubing, for an arrangement for monitoring an access to a patient


Coupon information is stored in a memory at a cable television station. The cable television station may simultaneously transmit multiple video signals, each representing different sources of television programming, over multiple television channels on the cable network. The video signal may at times, such as during a product advertisement or other offer, include an embedded coupon identifier. A coupon subsystem at the cable television station monitors each video signal and retrieves coupon information from a database when it detects a corresponding embedded coupon identifier and embeds the coupon information into the video signal before transmitting it. Coupon information may be embedded using teletext standards. A subscriber unit at the television viewer's site receives the television signal and includes a teletext decoder that extracts the coupon information. The television programming aurally or visually alerts the viewer that a coupon may be generated. If the viewer actuates an input device, such as a button on a television remote control, a printer generates a coupon bearing the coupon information. The coupon may have an anti-counterfeiting stripe. The subscriber unit may keep track of the coupons printed and prevent the user from printing those coupons again.

The present invention relates to an apparatus and method for generating a token, such as a product coupon or ticket, at a television viewer's site in response to a request by the television viewer.
Businesses may offer consumers coupons. Coupons are typically printed on paper and made available to consumers in various ways, including placing them in product containers and printing them in newspapers and magazines. In addition, devices coupled to cash registers or point-of-sale terminals are known that automatically print coupons when a shopper makes a purchase. A consumer may redeem a coupon at an establishment to obtain a cash discount for goods or services purchased there. If the establishment is a retailer of manufactured goods, the retailer, in turn, redeems the coupons by sending them to the manufacturer, who then reimburses the retailer for the amount of the discount. A retailer may utilize a redemption agency as a liaison between it and the manufacturer. A redemption agency sorts and tallies the coupons, validates the coupons as a safeguard against fraud and misredemption, determines the charges to the manufacturer, and compiles statistical information that may be useful to the manufacturer. Coupons, once redeemed, are destroyed to prevent re-use.
Manufacturers and other businesses have long advertised their products and services to consumers using the medium of television. Television commercials may be transmitted over cable networks and broadcast over the air. Coupons may be available for the advertised products and services.
A method for distributing coupons using signals transmitted via television channels is described in U.S. Pat. Nos. 5,249,044 and 5,128,752, both issued to Von Kohorn. The Von Kohorn system transmits a video image of product information, such as the manufacturer's name, the amount of the discount, and an identification number. The product information is displayed on a consumer's television. The consumer views this information on the television and then manually enters it into a hand-held electronic device using a keypad. The device has a printer that can be activated to print a coupon having some or all of the entered product information on it.
Coupons are valuable because they can be exchanged for cash, and fraud and misredemption are costly to manufacturers and retailers. Above all other considerations, a coupon distribution system should prevent duplication of a coupon. The Von Kohorn system, however, allows a user to print multiple copies of a coupon by entering the same product information multiple times. Another feature of the Von Kohorn system allows the electronic device to record the coupon transmission while the consumer is away from the television. Not only does recording a coupon encourage unlimited duplication, but it also fails to encourage the consumer to watch the televised commercial.
U.S. Pat. No. 5,070,404, issued to Bullock et al., describes a system that transmits two signals, each on a separate channel. The first signal carries coupon data, which are encoded along with a unique identifier into packets. The second signal carries an encoded "cue" signal. The coupon data are transmitted sequentially or periodically using a broadcast wheel. At the receiving end, the system receives the first signal and stores the decoded coupon data in memory. When the system receives the cue signal, it determines whether data having a matching identifier have been stored. If so, the system provides an indication to the user. The system may then retrieve the stored data and print a coupon.
The Bullock et al. system may inhibit fraud by preventing a user from printing coupons other than during the period in which the cue signal is transmitted. Nevertheless, monitoring and controlling the operation of the broadcast wheel inconveniences the broadcaster.
U.S. Pat. No. 5,285,278, issued to Holman, describes a system that encodes coupon data into the closed-captioning space of a standard television signal. At the receiving end, the system decodes the coupon data during display of the associated picture information. In contrast to the Bullock et al. system, encoding the television signal in this manner provides transparent operation from the broadcaster's point of view. Nevertheless, the system inextricably ties the coupon data to the source video. A new videotaped advertisement must be produced if the manufacturer wishes to change the terms of the coupon offer or withdraw the offer altogether. Furthermore, different videotapes must be produced if the manufacturer wishes to offer different coupons in different geographic regions in which the advertisement is to be televised, or to offer coupons in certain geographic regions and not in others.
It would be desirable to provide a system that distributes product coupons to consumers' sites using signals transmitted via television channels, while safeguarding against fraud and misredemption and while encouraging the consumers to watch the televised advertisements for the products. It would further be desirable in such a system to provide local control over the content of the coupon data at each regional broadcaster's site, yet without inconveniencing the broadcaster. These problems and deficiencies are clearly felt in the art and are solved by the present invention in the manner described below.

Apparatus and method for generating product coupons in response to televised offers


A digital image sequence with multiple image frames can be enhanced. An appearance graph can be determined from the digital image sequence. The appearance graph includes prime layer nodes. Each prime layer node can represent a distinctive visual style. A prime layer image sequence can be computed for each prime layer node that matches the visual style represented by the prime layer node. An enhanced image sequence can be generated by blending at least two prime layer image sequences as defined by the appearance graph.

The visual quality of a motion picture or video content can be improved by digitally processing image data in the temporal domain using sophisticated motion estimation or optical flow methods. In those methods, the movement of each pixel is tracked over numerous image frames, and pixels are enhanced for better quality attributes including noise reduction, deblurring, artifact removal, and detail enhancement. But, the computing process of temporal processing technology is very time consuming due to high computational complexities, and the computing time may exponentially increase as image resolution gets higher and as the motion tracking algorithms become more sophisticated. The process may take hours or days before any results are available from a computing job. If the resulting visual quality is not satisfactory, the user makes adjustments to certain render parameters and starts the tedious computation job over. As a result, it becomes very difficult for a typical post-production facility, which can be under a very tight time schedule and a very limited production budget, to fine tune the image quality to the satisfaction of a client.
And image content is often released across multiple types of displays, such as cinema, packaged media, cable television, or streaming to tablets and mobile devices. There can be vast differences with different types of display platforms, in terms of brightness, resolution, sharpness, color, contrast, bit rates, etc., or whether the display is direct view display or having an image that is being projected onto display, and image data is processed with consideration of those differences to maintain a consistent artistic style or visual appearance over multiple platforms. For example, a motion picture may be timed for a 30-foot wide matte cinema screen with an organic "film look." When the film is up converted for a large-format theater release, such as a 60-foot wide silver screen by IMAX®, the film grain preserved in the image data is further suppressed so that it does not get overly magnified. When the film is to be released through a streaming service, such as Netflix®, Amazon®, or Hulu®, for television viewing, the image data is often re-mastered for a much higher brightness level, for Rec. 709 color space instead of P3, and with a much higher level of data compression. Furthermore, the same film from the same streaming service provider may also look vastly different, partially due to the adaptive streaming protocol used to adjust the quality of a video stream according to available network bandwidth, and partially due to different display quality with user's devices. The recent rapid market adoption of latest UHD, HDR, WCG and HFR display technologies can further impact the quality gaps among different display platforms to whom the same content is to be released.

Enhancing image data with appearance controls


The invention relates to cellulosic moldings having very finely distributed zinc pigments after the dry-wet extrusion method. Cellulosic moldings formed in accordance with the inventive methods, compared to unmodified cellulose fibers, have a high degree of whiteness combined with greatly increased UV light absorption and a wash-resistant bactericidal effect, while at the same time having unrestricted textile processability. The cellulosic functional moldings produced according to the invention are particularly suited for use in textiles for clothing, technical textiles, recreation, medicine, and cosmetics.

Zinc oxide is colorless, and because it absorbs UV light below 380 nm wavelengths it is used as a UV absorber. It is similarly known that zinc compounds have bactericidal and fungicidal properties. In textiles, for example, this effect has been described for the production of a bactericidal polyamide filament, U.S. Pat. No. 7,074,482, a bactericidal PET fiber, CN1800454, modified cotton, CN1687509, viscose, JP8060431, viscose, acrylic fibers, PVC fibers, CN1442518, fibers comprising thermoplastic matrix and zinc sulfide, EP1 560 953 (whose United States equivalents are U.S. Patent Application Publication Nos. 2010/047366A1 and 2006/208390A1).
JP 08-060431 A describes viscose (rayon) fibers having antibacterial, deodorizing properties. The antibacterial properties are achieved by mixing the viscose with ceramic complexes. The ceramic complexes are obtained from a mixture of a) magnesium oxide, b) quartzite or zinc oxide and c) hornblende, zeolite or calcium oxide, which is subsequently fired. However, the maximum possible fraction of antibacterially active ceramic complexes in the viscose is relatively low. The coagulation and regeneration of the cellulose in the course of the production of viscose fibers always takes place in acidic coagulation and regeneration baths.
DE 198 02 588 A1 ( whose United States equivalent is U.S. Pat. No. 6,514,609) provides luminescent fibers, more particularly luminescent cellulosic fibers obtainable by the viscose process or by the NMMO process. They contain inorganic luminophore pigments which, on stimulation with visible or ultraviolet radiation, preferably display a phosphorescent effect. Transition metal- or lanthanoid-doped zinc sulfides, oxides, oxysulfides, silicates or aluminates are mentioned specifically. Silver-doped zinc sulfides display blue fluorescence for example. However, transition elements or lanthanoid elements can bring about an autocatalyzed, strongly exothermic decomposition of the NMMO.
EP 0 043 325 A1 ( whose United States equivalent is U.S. Pat. No. 4,280,925) describes filter materials comprising cellulose ester material which contain zinc sulfide or zinc oxide. The filter materials can be used to filter heavy metal ions, such as silver, mercury, lead, copper or cadmium out of aqueous solutions. The cellulose esters mentioned are cellulose acetate, cellulose butyrate and cellulose propionate and also mixtures thereof.
Moldings, specifically fibers and filaments, with antibacterial or antifungal activity are disclosed in WO 2004/044284 A1( whose United States equivalents are United States Patent Application Publication Nos. 2010/047366A1 and US 2006/208390A1). The activity is achieved via a zinc sulfide content. The proportion of zinc sulfide ranges from 0.01% to 10% by weight, based on the weight of the polymeric material which forms the molding. Polymeric materials specifically mentioned are polyurethanes, polyesters, polyamides, acrylic polymers, polyolefins, cellulose or cellulose esters.
DE 44 26 966 A1 discloses a process for producing highly filled and oriented cellulosic fibers and films by a specific dry-wet spinning process. The fillers used are finely divided substances, for example metal powders or ceramic substances. The proportion of filler can be up to more than 500% by weight, based on the weight of the cellulose.
DE 10 2007 019 768 A1 ( whose United States equivalent is United States Patent Application Publication No. US 2010/124861) discloses a process for producing antibacterially additized cellulosic fibers of high whiteness. The fibers are produced by a lyocell process. The antibacterial performance is achieved through the addition of silver-containing nanoparticles.
The processes described all lead to moldings wherein the effect of the zinc compounds decreases greatly with the number of washes, and often textile processing is severely curtailed at high concentrations of zinc compounds.


An implantable cardioverting/defibrillating pacemaker and method for treating arrhythmias of a patient's heart are disclosed. Bradycardia support pacing is initially provided at a normal standby rate, in the absence of a tachycardia. Upon detection and confirmation of a tachycardia, antitachycardia therapy in the form of antitachycardia pacing pulse therapy and/or cardioversion or defibrillation therapy is delivered to the heart. Thereafter, upon reversion of the tachycardia, bradycardia support pacing is again delivered to the heart but at a greater rate than the earlier normal standby rate and only for a predetermined time period. At the end of such time period, the bradycardia support pacing rate is returned to the normal standby rate, either directly or in decremental steps.

Implantable pacemaker/defibrillator devices are well known to the medical profession. One early example of such a device is U.S. Pat. No. 3,857,398 to L. Rubin. The Rubin device utilizes separate circuitries in dealing with the different functions of pacing and defibrillation. There is no provision in the Rubin device for changing the bradycardia standby rate. All of Rubin's bradycardia pacing pulses are apparently delivered at the same rate. Many advances have been made after Rubin in the development of devices and techniques for providing effective medical responses to a variety of heart disorders of arrhythmias.
Recent efforts have resulted in the development of more sophisticated implantable pacing and defibrillating devices. One example of such a device is disclosed in U.S. Pat. No. 4,869,252 to N. L. Gilli, entitled "Apparatus and Method for Controlling Pulse Energy in Antitachyarrhythmia and Bradycardia Pacing Device". This Patent discloses an apparatus which provides bradycardia support pacing at different energy levels, including a higher pulse energy for a period following successful antitachycardia therapy, and a lower level during normal bradycardia support pacing. Capture is more efficient at the higher energy level since the heart has been traumatized by the tachycardia and/or the antitachycardia therapy. In the Gilli patent, again, the bradycardia therapy is delivered at a constant programmed standby rate.
The implantable pacing and defibrillating device disclosed in U.S. Pat. No. 4,940,054 to R. Grevis et al., entitled "Apparatus and Method for Controlling Multiple Sensitivities in Arrhythmia Control System Including Post Therapy Pacing Delay," is another example of a more sophisticated device of this type. Following antitachycardia therapy, which may be antitachycardia pacing or cardioversion/defibrillation, there is a pause or post therapy delay for a period of time substantially greater than a normal standby interval prior to the commencement of bradycardia support pacing. However, when bradycardia support pacing is required after antitachycardia therapy, it is delivered at a constant rate.
A problem that is common to all existing antitachyarrhythmia devices is their failure, after reverting tachycardias, to compensate patients who are dependent on bradycardia support pacing for the hemodynamic compromise resulting from the tachycardia and/or the antitachycardia therapy.
A tachycardia and/or antitachycardia therapy can temporarily reduce the heart's pumping efficiency. If so, the hemodynamic competence of a bradycardia support pacing-dependent patient being paced at a constant standby rate is impaired for as long as the pumping efficiency remains reduced. This can be traumatic to a patient and presents a real problem to some patients that are currently using existing devices.
It is therefore a primary object of the present invention to provide an improved apparatus and a method for treating cardiac arrhythmias which, following reversion from tachycardia, compensate for hemodynamic compromise experienced during tachycardia and/or following antitachycardia therapy.
It is a further object of the invention to provide an improved apparatus and method for treating cardiac arrhythmias which delivers antitachycardia pacing therapy and cardioversion/defibrillation therapy when needed and includes temporarily increasing the bradycardia support pacing rate following the delivery of antitachycardia therapy.
Further objects and advantages of this invention will become apparent as the following description proceeds.

Implantable pacemaker/cardioverter/defibrillator device and method incorporating multiple bradycardia support pacing rates


The present invention relates to methods for treating inflammation in body tissues. More specifically, certain disclosed methods relate to selectively inducing apoptosis in inflammatory immune cells. The methods are particularly suitable for treating inflamed atherosclerotic plaques. The techniques generally involve heating the cells with a catheter that is equipped to produce infrared radiation. The cells are heated for a sufficient time and at a sufficient temperature to induce programmed cell death.

A. Field of the Invention
This invention relates to the treatment of harmful inflammation in body tissue by exposing the inflammatory cells to heat. In one method, heat is applied to an inflamed atherosclerotic plaque by means of a catheter that is equipped with a heating source. Such heating can be very mild (38.degree. C.-40.degree. C.) so as to quiesce macrophages and other inflammatory cells, or moderate (41.degree.-44.degree. C.) to induce programmed cell death, apoptosis, but not hot enough to cause necrosis and subsequent inflammation.
B. Description of Related Art
Coronary artery disease is a leading cause of death in industrialized countries. It is manifested by athersclerotic plaques, which are thickened areas in vessel walls. A plaque is an accumulation of cholesterol, proliferating smooth muscle cells and inflammatory cells covered by cellular secretions of collagen that form a cap over the plaque in the vessel wall. Macrophages migrate into and accumulate in a plaque causing inflammation. Inflamed plaques are most susceptible to ruptures and the formation of blood clots. Falk, E. (1995).
Atherosclerotic plaques are thought to develop in response to irritation or biochemical damage of the endothelial cells that line blood vessel walls. Agents that are known to damage these cells include cigarette smoke, high serum cholesterol (especially in the form of oxidized low density lipoprotein), hemodynamic alterations (such as those found at vessel branch points), some viruses (herpes simplex, cytomegalovirus) or bacteria (e.g., Chlamydia), hypertension, and some plasma hormones (including angiotensisn II, norepinephrine) and homocysteine. Atherosclerotic plaques grow slowly over many years in response to the cumulative injury of endothelial cells. Ross (1993), Berliner (1995).
Typically, several dozen plaques are found in arteries afflicted with this disease. It is the rupture of these plaques that brings about the terminal stage of the disease. The rupture causes a large thrombus (blood clot) to form on the inside of the artery, which may completely occlude the blood flow through the artery, thereby injuring the heart or brain. Falk, E. (1995).
In most cases of terminal coronary artery disease, only one of several plaques ruptures. Rupture typically is caused by inflammatory cells, primarily macrophages, that lay beneath the surface collagen layer of the plaques. These cells release enzymes that tend to degrade the cap. Once a plaque ruptures, blood clots are formed and it is these clots that are believed to be responsible for over one half of all heart attacks and stokes. Falk, E. (1995); Buja (1994).
Techniques have been developed to identify those plaques that are most likely to rupture because of inflammation. See U.S. patent application Ser. No. 08/717,449, which is specifically incorporated by reference herein. The most common treatment for these plaques is balloon angioplasty. However, this method is known to result in about a 5% incidence of complete thrombotic occlusion and a 30-40 % incidence of vessel reclosure due to restenosis. It is clear that in many cases balloon angioplasty causes cellular injury and only temporarily eliminates the danger from an inflamed plaque until the advent of a secondary inflammatory response. Casscells (1994).
It has been shown that macrophages have a life span of only about a week or two in the vessel wall. Katsuda (1993). Typically, monocytes enter the atherosclerotic plaque, divide once, and contribute to plaque development by their ability to oxidize low density lipoprotein cholesterol and to release factors which cause smooth muscle proliferation and angiogenesis. The cells then undergo apoptosis, which is an active process of programmed cell death. This process differs from necrosis in that apoptosis requires the expenditure of energy, and the synthesis of new RNA and proteins in all but the inflammatory cells, the active cleavage of DNA and the shrinkage and involution of the cell with very little inflammation. Steller (1995); Nagata (1995); Thompson (1995); Vaux (1996).
Apoptosis is a form of programmed cell death in which the dying cells retain membrane integrity and are rapidly phagocytosed and digested by macrophages or by neighboring cells. It occurs by means of an intrinsic cellular suicide program that results in DNA fragmentation and nuclear and cytoplasmic condensation. The dead cells are rapidly cleared without leaking their contents and therefore little inflammatory reaction follows. It can be induced by the withdrawal of growth factors and to some extent by factors which can also cause necrosis such as extreme lack of oxygen or glucose, heat, oxidation and other physical factors.
Previously no method was known for selectively inducing apoptosis in macrophages or other inflammatory cells in a blood vessel without also inducing apoptosis in beneficial endothelial cells. Known methods for inducing apoptosis were systemic, including treatments with chemicals and elevated temperatures. Such methods are not useful as therapeutic methods because of the risk that apoptosis will develop in healthy tissue.
A number of studies have shown that heat can induce programmed cell death. Kunkel (1986) have found that indomethacin inhibits macrophage synthesis of prostaglandin but enhances macrophage production of TNF-.alpha., which suggests that heating may have advantages over indomethacin as an anti-inflammatory treatment. Preventing the synthesis of prostaglandin, which serve as feedback inhibitors of macrophage function, limits the anti-inflammatory utility of indomethacin and presumably other inhibitors of cyclo-oxygenase. Field and Morris (1983) surveyed many cell types and found that the time needed to kill cells at 43.degree. C. varied from four minutes in mouse testis, to 32 minutes in rat tumor 96 in vivo, to 37 minutes for mouse jejunum, to 75 minutes for rat skin, 210 minutes for mouse skin and 850 minutes for pig skin. Numerous other cell types were also studied. They observed that, above 42.5.degree. C., an increase of 1.degree. C. produces a similar effect as doubling the duration of heat exposure. Wike-Hooly (1984) found that a low pH enhanced hyperthermic cell killing, as did a low glucose or insulin exposure and that nitroprusside also increased the cell mortality caused by hyperthermia. Raaphorst (1985) and Belli (1988) studied Chinese hamster lung fibroblasts and found that 45.degree. C. heat and radiation were synergistic in cell killing. Raaphorst (1985) also found S-phase to be heat-sensitive and least radiosensitive, while in G1 and G2 the opposite was true. Klostergard (1989) found that cytotoxicity of macrophages was decreased by heating to 40.5.degree. C. for 60 minutes. Westra and Dewey (1971) found that in CHO cells S phase was more sensitive to heating to 45.5.degree. C. than was G1 phase. M phase was intermediate. In contrast, radiation killed cells preferentially in phases G1 and M1. Fifty percent of asynchronous (cycling) CHO cells were killed by a 20 minute heat treatment at 43.5.degree. C. Freeman (1980) found that the sensitivity of CHO cells to 41.degree. C. to 45.5.degree. C. was increased with acidosis and that thermotolerance was induced by exposure to 42.degree. C. for 250 minutes. Haverman and Hahn (1982) used an inhibitor of oxidative phosphorylation and found that CHO cells were thereby more prone to heat-induced death using 43.degree. C. for one hour. Preheating, however, led to tolerance. These experiments could not determine whether hyperthermia increased ATP utilization or inhibited its synthesis. Gerweck (1984) found that CHO cells were more easily killed by 44.degree. C. (20% died after a 15-minute exposure) when ATP was depleted by hypoxia and hypoglycemia, but neither condition alone had an effect. Lavie (1992) found that peritoneal macrophages from older mice tend to die at 42.5.degree. C. for 20 minutes but not macrophages from younger mice. Papdimitriou (1993) found that most peritoneal murine macrophages undergo apoptosis with a five-hour exposure to 41.degree. C., but few entered apoptosis at 30.degree. C. Most circulating monocytes did not undergo apoptosis at 41.degree. C., with a five-hour exposure. Mangan (1991) reported that TNF alpha and interleukin-1 beta prevent macrophage apoptosis. Chen (1987) reported that heat in the range of 41.degree. C. to 43.degree. C. stimulated macrophage production of prostaglandins. Prostaglandins serve to suppress macrophage production and phagocytosis. Heat did not decrease prostaglandin release from tumor cell line or from fibroblasts. They found that macrophage death began at 41.degree. C. with a four-hour exposure. A six-hour exposure to 43.degree. C. killed half the macrophages. Ensor (1995) found no macrophage cell death after six hours at 40.degree. C., (vs. 37.degree. C.) but at 43.degree. C. only 4% of cells were viable at six hours. O'Hara (1992) found that bone marrow macrophages survive 15 minutes at 45.degree. C. if they have been preheated for 110 minutes to 42.5.degree. C. Fouqueray (1992) found that exposing rat peritoneal macrophages to 39.degree. C. to 41.degree. C. for 20 minutes decreased synthesis of IL-1 and TNF-.alpha.. Circulating monocytes were less sensitive to heat than glomerular or peritoneal macrophages. This degree of heating did not kill the macrophages. Hamilton (1995) found that the cancer drug bleomycin blocked expression of HSP-72 in human alveolar macrophages in response to exposure to 39.8.degree. C. This was a relatively specific effect since there was no change in overall protein synthesis and, moreover, the effect appeared to be post-transcriptional, since there was no change in mRNA levels for HSP-72. The bleomycin exposure did not cause much necrosis, but it caused marked DNA fragmentation characteristic of apoptosis. Wang (1995) found that induction of HSP-72 prevented necrosis in human endothelial cells exposed to activated neutrophils. The activated neutrophils caused necrosis of endothelial cells that had been exposed to 30 to 60 minutes of heat shock at 42.degree. C., an exposure which by itself did not induce necrosis or apoptosis. Wang (1997) found that endothelial cells did not go to apoptosis with a 45-minute exposure to 42.degree. C. or with exposure to TNF-.alpha., but exposure to both did trigger apoptosis. TNF-.alpha. resulted in generation of reactive oxygen species, which the authors believe may be required, together with heat shock, to induce apoptosis in endothelial cells. Kim (1997) found that nitric oxide protected cultured rat hepatocytes from TNF-.alpha. induced apoptosis by means of inducing HSP-70. Belli (1963) observed that heating enhances cell susceptibility to radiation killing.
Cytokines are also known to influence apoptosis in macrophages and other leukocytes. William (1996) found that apoptosis in neutrophils was promoted by heat, TNF-.alpha., or endotoxin but inhibited by LPS, GMCSF and IL-2. Biffl (1996) found that IL-6 also delayed neutrophil apoptosis. Prins (1994) found in human fat tissue explants adipocytes underwent apoptosis within 24 hours of a 60-minute exposure to 43.degree. C. and then underwent phagocytosis, suggesting that at least some macrophages survived longer than some adipocytes. O'Hara (1992) showed that granulocyte-macrophage precursors take longer (T.sub.1/2 =36 min.) to become heat-tolerant than do stem cells or erythrocyte precursors from bone marrow. Verhelj (1996) found that 50 percent of confluent, nondividing, bovine aortic endothelial cells underwent apoptosis by 12 hours at 43.degree. C., versus 41.degree. C. for dividing human monoblastic leukemia of the U937 line, but this difference could well be attributable to the difference in age of the cells, cycling rate or species. D. Elkon and H. E. McGrath (1981) presented some evidence that granulocyte monocyte stem cells do not take as long as other cells to be killed at a temperature of 42.5.degree. C. Blackburn (1984) reported that circulating monocyte precursors are more sensitive to heat than are those from bone marrow. Kobayashi (1985) reported that granulocyte-macrophage progenitor cells were more sensitive to 60 minutes at 42.degree. C. when the marrow was regenerating (during cell division) than when it was stationary, but this is a finding in all cell types. Cohen (1991) found no difference in heat tolerance of epithelial cells and airway macrophages, as measured by immediate release of LDH and chromium-51.
A number of studies have studied the relationship between heat shock and cell killing. Nishina (1997) found that the stress-activated protein kinases (also known as the Jun N-terminal kinases) are activated in response to heat shock and other cell stresses. A knockout of one of these genes (SEK-1) resulted in fewer CD4+, CD8+thymocytes. Pizurki and Polla (1994) found that cAMP increased synthesis of heat-shock proteins by heated macrophages. Reddy (1982) found that heat shock of murine macrophages increased their production of superoxide but did not change their production of hydrogen peroxide or their microbicidal activity. Sivo (1996) found that heat shock acted in a fashion similar to glucocorticoids in inhibiting mouse peritoneal macrophages and increased the transfer of glucocorticoid receptors to the nucleus. Snyder et. al (1992) found that mouse peritoneal macrophages synthesized heat-shock proteins (HSPs) maximally after a 12-minute exposure to 45.degree. C.; HSPs were only found two to six hours after heat treatment. They found no HSP-70 at 42.degree. C. or 43.degree. C. At 2 and 24 hours after heating, phagocytosis was normal. They did not mention whether macrophages entered apoptosis with this treatment and that the same treatment (12 minutes at 45.degree. C.) decreased TNF alpha and IL-1 RNA synthesis in mouse peritoneal macrophages. Pizurki et. al (1994) reported that circulating human monocytes express HSPs two hours after 20 minutes of exposure of 45.degree. C. and that expression was enhanced in cAMP and unaffected by indomethacin.
A number of studies have shown that heating and chemical treatments change the activity of immune cells. Chen (1987) found that heating murine macrophages to 41.degree. C. to 43.degree. C. for one hour caused them to synthesize and release prostaglandins of the E type. Fouqueray (1992) found that a 20-minute exposure of rat peritoneal macrophages to 39.degree. C. to 41.degree. C. decreased synthesis of tumor necrosis factor alpha and interleukin-1 within two hours, but monocytes circulating in the blood were less sensitive to heating than were the tissue macrophages. Ribeiro (1996) confirmed that heat exposure decreases macrophage release of TNF alpha both in vitro and in vivo. Kunkel (1986) showed that indomethacin inhibited lipopolysaccharide (LPS)-induced synthesis of prostaglandins by macrophages (and inhibited heat-induced PGEs Chen, 1987) but enhanced macrophage production of TNF-.alpha. in response to LPS. Morange M. (1986) found that HSPs were induced at lower temperatures when cells were exposed to interferon-alpha and interferon-beta. Ensor (1995) reported that exposing a macrophage cell line to 40.degree. C. for 30 minutes prevented (within six hours) synthesis and release of TNF-.alpha. in response exposure to LPS. The half-life of TNF-.alpha. mRNA was shortened. There was no change in the levels of mRNA for GAPDH, .beta.-actin or IL-6. HSP-72 was increased at 43.degree. C. The same authors previously showed that in human macrophages TNF expression was suppressed at 38.5.degree. C., but HSP-72 was increased only above 40.degree. C. Papadimitriou showed that macrophage apoptosis was minimal at 39.degree. C. but substantial at 41.degree. C.
Although the cellular phenomenon of apoptosis has been studied in some detail in tissue culture, no studies have been directed toward developing that technique for the treatment of inflammation. New methods are needed for treating inflamed body tissues and in particular to the treatment of atherosclerotic plaques to prevent rupture. Such methods should not induce an inflammatory response and should be capable of eliminating or neutralizing macrophages or other inflammatory cells without damaging blood vessel walls. Novel methods for selectively inducing apoptosis are also needed. Such methods will be useful in preventing the rupture of atherosclerotic plaques and therefore reduce the risk of death from myocardial infarction or stroke.


A spectral feature extracting engine, chirp detecting engine, and target classifying engine with corresponding method, system, and computer product are provided. Given a “noisy” signal having multiplicative and additive noise, the spectral feature extracting engine extracts spectral features from the noisy signal in the form of a spectral detection density. The extraction includes identifying an initial detection by comparing the spectral content of a subject time-frequency slice with an initial detection threshold calculated from a set of time-frequency slices, and determining the spectral detection density as a function of a number of identified initial detections and number of compared time-frequency slices. Based on the spectral detection density of the noisy signal, the chirp detecting engine detects multiple channel-induced and target-induced chirps present in the noisy signal and the target classifying engine classifies a target from the noisy signal.

A chirp is characterized by a frequency that is swept across a spectrum. The sweep can be of a first or higher order. When it is of the first order, the signal is a linear chirp. If it is second order, then the signal is a quadratic chirp and so on. Chirps do not lend themselves to analysis via classical Fourier transform techniques like the fast Fourier transform (FFT). The FFT is a proper tool to analyze signals with invariant or slowly varying frequencies over an observation interval. Analyzing signals with time-varying frequencies, however, requires a different set of tools.
A Short-Time Fourier Transform (STFT) is well suited and widely used for analyzing signals with time-varying frequencies. Even with STFT, however, analyzing a time-frequency spectrum like that of FIG. 5 for a chirp or for spectral features indicative of a chirp is arduous. What may be visually obvious, however, is not as easily attained algorithmically. Beside the fact that a chirp detecting algorithm has to perform a two-dimensional search of the entire spectrum, the algorithm has to make decisions as to what is a chirp or what is indicative of a chirp on a large number of pixels (i.e., spectral information or data). It seems advantageous to analyze a signal in a transform domain where a chirp is a localized signal rather than one that is distributed across the entire spectrum.
Academic work in the signal processing has produced several algorithms that are designed to detect or estimate chirps in a localized manner. The work includes a maximum likelihood technique, Discrete Chirp Fourier transform, and the cubic phase transform. These techniques, however, are limited to signals having a single chirp present, and a noise model that is additive and Gaussian in nature. These techniques are inadequate for detecting or estimating chirps in signals containing multiple chirps and having noise that is multiplicative in nature.
Particularly challenging is the presence of broadband noise that can clutter the entire spectrum. By comparison, a chirp occupies a finite region across frequency. Broadband noise has a spectral signature that spreads energy across the entire spectrum. This type of noise may be uniform across frequency but its time spread extends for the duration of the noise burst in the time domain signal.

Extracting spectral features from a signal in a multiplicative and additive noise environment


A base station can select orthogonal frequency-division multiplexing (OFDM) numerologies that define subcarrier spacing values based on attributes associated with one or more services that a user equipment (UE) is using. The base station can use the selected OFDM numerologies for transmission associated with the services. When the UE is using multiple services simultaneously, the base station can select the same or different OFDM numerologies for the multiple services.

Multiplexing can be used to combine and transport multiple signals over a channel bandwidth. One type of multiplexing often used in wireless access technologies is orthogonal frequency-division multiplexing (OFDM). OFDM transmits data in multiple subcarriers within a larger channel bandwidth. To mitigate interference between the subcarriers, the subcarriers can be spaced apart according to a subcarrier spacing.
Some wireless access technologies, such as Long Term Evolution (LTE), use an OFDM numerology with a fixed subcarrier spacing. However, other wireless access technologies, such as fifth generation (5G) New Radio (NR), use flexible OFDM numerologies that allow scalable subcarrier spacing. Different subcarrier spacing values in these flexible OFDM numerologies can have different benefits in different situations.


Injectable compositions having improved injectability. The injectable compositions include microparticles suspended in an aqueous injection vehicle having a viscosity of at least 20 cp at 20xc2x0 C. The increased viscosity of the injection vehicle that constitutes the fluid phase of the suspension significantly reduces in vivo injectability failures. The injectable compositions can be made by mixing dry microparticles with an aqueous injection vehicle to form a suspension, and then mixing the suspension with a viscosity enhancing agent to increase the viscosity of the fluid phase of the suspension to the desired level for improved injectability.

1. Field of the Invention
The present invention relates to preparation of injectable compositions. More particularly, the present invention relates to injectable suspensions having improved injectability, and to methods for the preparation of such injectable suspensions.
2. Related Art
Injectable suspensions are heterogeneous systems that typically consist of a solid phase dispersed in a liquid phase, the liquid phase being aqueous or nonaqueous. To be effective and pharmaceutically acceptable, injectable suspensions should preferably be: sterile; stable; resuspendable; syringeable; injectable; isotonic; and nonirritating. The foregoing characteristics result in manufacturing, storage, and usage requirements that make injectable suspensions one of the most difficult dosage forms to develop.
Injectable suspensions are parenteral compositions in that they are introduced into an organism or host by means other than through the gastrointestinal tract. Particularly, injectable suspensions are introduced into a host by subcutaneous (SC) or intramuscular (IM) injection. Injectable suspensions may be formulated as a ready-to-use injection or require a reconstitution step prior to use. Injectable suspensions typically contain between 0.5% and 5.0% solids, with a particle size of less than 5 xcexcm for IM or SC administration. Parenteral suspensions are frequently administered through needles about one-half to two inches long, 19 to 22 gauge, with an internal diameter in the range of 700 to 400 microns, respectively.
To develop an effective and pharmaceutically acceptable injectable suspension, a number of characteristics must be evaluated. These characteristics include syringeability, injectability, clogging, resuspendability, and viscosity. As will be readily apparent to one skilled in the art, other characteristics and factors should be considered in developing an injectable suspension (see, for example, Floyd, A. G. and Jain, S., Injectable Emulsions and Suspensions, Chapter 7 in Pharmaceutical Dosage Forms: Disperse Systems Vol. 2, Edited by Lieberman, H. A., Rieger, M. M., and Banker, G. S., Marcel Dekker, New York (1996), the entirety of which is incorporated herein by reference and referred to herein as xe2x80x9cthe Floyd et al. Chapterxe2x80x9d).
Syringeability describes the ability of an injectable suspension to pass easily through a hypodermic needle on transfer from a vial prior to injection. It includes characteristics such as ease of withdrawal, clogging and foaming tendencies, and accuracy of dose measurements. As described in the Floyd et al. Chapter, increase in the viscosity, density, particle size, and concentration of solids in suspension hinders the syringeability of suspensions.
Injectability refers to the performance of the suspension during injection. Injectability includes factors such as pressure or force required for injection, evenness of flow, aspiration qualities, and freedom from clogging.
Clogging refers to the blockage of syringe needles while administering a suspension. It may occur because of a single large particle, or an aggregate that blocks the lumen of the needle due to a bridging effect of the particles. Clogging at or near the needle end may be caused by restrictions to flow from the suspension. This may involve a number of factors, such as the injection vehicle, wetting of particles, particle size and distribution, particle shape, viscosity, and flow characteristics of the suspension.
Resuspendability describes the ability of the suspension to uniformly disperse with minimal shaking after it has stood for some time. Resuspendability can be a problem for suspensions that undergo xe2x80x9ccakingxe2x80x9d upon standing due to settling of the deflocculated particles. xe2x80x9cCakingxe2x80x9d refers to a process by which the particles undergo growth and fusion to form a nondispersible mass of material.
Viscosity describes the resistance that a liquid system offers to flow when it is subjected to an applied shear stress. A more viscous system requires greater force or stress to make it flow at the same rate as a less viscous system. A liquid system will exhibit either Newtonian or non-Newtonian flow based on a linear or a non-linear increase, respectively, in the rate of shear with the shearing stress. Structured vehicles used in suspensions exhibit non-Newtonian flow and are typically plastic, pseudoplastic, or shear-thinning with some thixotropy (exhibiting a decrease in viscosity with an increase in the rate of shear).
In design of injection vehicles, viscosity enhancers are added in order to retard settling of the particles in the vial and syringe. However, viscosity is typically kept low, in order to facilitate mixing, resuspension of the particles with the vehicle, and to make the suspension easier to inject (i.e., low force on the syringe plunger). For example, Lupron Depot from TAP Pharmaceuticals (mean particle size of approximately 8 xcexcm) utilizes an injection vehicle with a viscosity of approximately 5.4 cp. The fluid phase of a suspension of Decapeptyl from DebioPharm (mean particle size of approximately 40 xcexcm), when prepared as directed, has a viscosity of approximately 19.7 cp. Conventional parenteral suspensions are dilute, with limitations for viscosity because of syringeability and injectability constraints. See, for example, the Floyd, et al. Chapter noted above.
Injectable compositions containing microparticle preparations are particularly susceptible to injectability problems. Microparticle suspensions may contain 10-15% solids, as compared with 0.5-5% solids in other types of injectable suspensions. Microparticles, particularly controlled release microparticles containing an active agent or other type of substance to be released, range in size up to about 250 xcexcm, as compared with a particle size of less than 5 xcexcm recommended for IM or SC administration. The higher concentration of solids, as well as the larger solid particle size, make it more difficult to successfully inject microparticle suspensions. This is particularly true since it is also desired to inject the microparticle suspensions using as small a needle as possible to minimize patient discomfort.
Thus, there is a need in the art for an injectable composition with improved injectability. There is a particular need in the art for an injectable composition that solves the injectability problems associated with microparticle suspensions. The present invention, the description of which is fully set forth below, solves the need in the art for such injectable compositions.
The present invention relates to injectable compositions having improved injectability, and to methods for the preparation of such injectable compositions. In one aspect of the invention, a composition suitable for injection through a needle into a host is provided. The composition comprises microparticles having a polymeric binder, with a mass median diameter of at least about 10 xcexcm. The composition also includes an aqueous injection vehicle (the injection vehicle not being the aqueous injection vehicle that consists of 3% by volume sodium carboxymethyl cellulose, 1% by volume polysorbate 20, 0.9% by volume sodium chloride, and a remaining percentage by volume of water). The microparticles are suspended in the injection vehicle at a concentration of greater than about 30 mg/ml to form a suspension, the fluid phase of the suspension having a viscosity of at least 20 cp at 20xc2x0 C. In other embodiments, the fluid phase of the suspension has a viscosity at 20xc2x0 C. of at least about 30 cp, 40 cp, 50 cp, and 60 cp. The composition may also comprise a viscosity enhancing agent, a density enhancing agent, a tonicity enhancing agent, and/or a wetting agent. The composition can be administered to a host by injection.
In another aspect of the present invention, a method of making a composition suitable for injection through a needle into a host is provided. The method comprises:
(a) providing microparticles comprising a polymeric binder, said microparticles having a mass median diameter of at least about 10 xcexcm;
(b) providing an aqueous injection vehicle having a viscosity of at least 20 cp at 20xc2x0 C., wherein said injection vehicle is not the aqueous vehicle consisting of 3% by volume sodium carboxymethyl cellulose, 1% by volume polysorbate 20, 0.9% by volume sodium chloride, and a remaining percentage by volume of water; and
(c) suspending the microparticles in the aqueous injection vehicle at a concentration of greater than about 30 mg/ml to form a suspension.
In a further aspect of the present invention, another method for preparing a composition suitable for injection through a needle into a host is provided. In such a method, dry microparticles are mixed with an aqueous injection vehicle to form a first suspension. The first suspension is mixed with a viscosity enhancing agent to form a second suspension. The viscosity enhancing agent increases the viscosity of the fluid phase of the second suspension. The first suspension may be withdrawn into a first syringe, prior to mixing with the viscosity enhancing agent. The first suspension may be mixed with the viscosity enhancing agent by coupling the first syringe containing the first suspension to a second syringe that contains the viscosity enhancing agent. The first suspension and the viscosity enhancing agent are then repeatedly passed between the first and second syringes.
In yet a further aspect of the present invention, a method for administering a composition to a host is provided. The method comprises:
(a) mixing dry microparticles with an aqueous injection vehicle to form a first suspension;
(b) mixing the first suspension with a viscosity enhancing agent to form a second suspension, wherein the viscosity enhancing agent increases the viscosity of the fluid phase of the second suspension; and
(c) injecting the second suspension into the host.
In still a further aspect of the present invention, another method for administering a composition to a host is provided. The method comprises:
(a) mixing dry microparticles with an aqueous injection vehicle to form a suspension, wherein the aqueous injection vehicle has a viscosity at 20xc2x0 C. of less than about 60 cp;
(b) changing the viscosity of the fluid phase of the suspension;
(c) withdrawing the suspension into a syringe; and
(d) injecting the suspension from the syringe into the host.
In a further aspect of the invention, step (b) is carried out by changing the temperature of the fluid phase of the suspension. In another aspect, step (c) is performed prior to step (b). Step (b) may be carried out by adding a viscosity enhancing agent to the suspension in the syringe to thereby increase the viscosity of the fluid phase of the suspension.
In still a further aspect of the invention, a method for preparing a composition suitable for injection through a needle into a host is provided. The method comprises:
(a) mixing dry microparticles with an aqueous injection vehicle that comprises a viscosity enhancing agent to form a suspension;
(b) removing water from the suspension; and
(c) reconstituting the suspension with a quantity of sterile water for injection to form an injectable suspension, wherein the quantity of sterile water for injection is sufficient to achieve a viscosity of a fluid phase of the injectable suspension that provides injectability of the composition through a needle ranging in diameter from 18-22 gauge.
A feature of the present invention is that the injectable compositions can be used to inject varying types of microparticles, and varying types of active agents or other substances, into a host.
A further feature of the present invention is that it allows microparticles to be wetted to achieve a homogeneous suspension, while improving injectability into a host and reducing in vivo injectability failures.
The present invention advantageously provides medically acceptable injectability rates for high concentration suspensions, and for suspensions having large particle size.
The present invention also advantageously provides an efficient method of improving in vivo injectability without introducing microbial contamination or compromising aseptic conditions.

Preparation of injectable suspensions having improved injectability

Alkermes Controlled Therapeutics, Inc. I


The invention relates to additives to improve the reversibility of a carbon electrode of a lithium ion secondary electrochemical generator. These additives are composed of cyclic or non-cyclic xcex1-halogenated esters such as xcex1-bromo-xcex3-butyrolactone or methyl chloroformiate. They may be added to the electrolyte at a rate of 0.5 to 3% by volume or adsorbed on the carbon electrode to form a passivation film on said electrode during the first use of the generator.

The present invention relates to the use of additives to improve the reversibility, in the presence of propylene carbonate, of a carbon electrode of a lithium ion secondary electrochemical generator.
It particularly applies to the production of specific high-power secondary generators, which are of great interest for the development of portable devices and, on a more long-term level, for the production of electric vehicles.
At the present time, for these applications, the choice seems to focus on lithium ion secondary electrochemical generators using a carbon compound, particularly graphite, as a negative electrode.
Indeed, graphite is currently the most promising carbon since, in its lamellar structure, it can accept up to one lithium atom for six carbon atoms, at potentials close to that of metallic lithium. However, lithium can only be inserted into graphite in a reversible manner in a few appropriate electrolytes. In this way, it is difficult to use propylene, in spite of its good properties, in such generators, since it has the disadvantage of decomposing in the graphite structure and thus preventing the insertion of lithium in the graphite electrode.
A. N. Dey and B. P. Sullivan reported this problem of the decomposition of propylene carbonate in the graphite electrode, in J. Electrochem. Soc., 117, 1970, pages 222-224, [1]. Similarly, M. Arakawa and J. Ichi Yamaki reported this problem and proposed a propylene carbonate decomposition schedule in J. Electroanal. Chem., 219, 1987, p. 273-280, [2].
To, overcome these difficulties, D. Billaud, A. Naji and P. Willmann proposed in J. Chem. Soc., Chem. Commun., 1995, pages 1867 and 1868, [63], to subject the graphite electrode to a pre-treatment to form on said electrode a protective coat impervious to propylene carbonate molecules but enabling the diffusion of lithium ions. This protective coat is formed by electrochemical reduction, in an electrolyte comprising ethylene carbonate and lithium perchlorate.
Another solution to avoid this disadvantage was described by Z. X. Shu, R. S. McMillan, J. J. Murray and I. J. Davidson in J. Electrochem. Soc., 143, No. 7, July 1996, p. 2230-2235, [4]. In this case, an electrolyte mixture of chloroethylene carbonate and propylene carbonate is used.
The first solution described in reference [3] has the disadvantage of requiring an electrode pre-treatment step, before the electrode is used in the secondary electrochemical generator with a propylene carbonate-based electrolyte.
The second solution described in reference [4] has the disadvantage of requiring a significant proportion of additive since chloroethylene carbonate, chloro-EC, with the formula:
generally represents 50% by volume of the electrolyte, and this proportion of chloro-EC must not be less than 30%.
The precise purpose of the present invention is to improve the reversibility of the insertion of lithium in a carbon electrode of a lithium ion secondary electrochemical generator using an electrolyte comprising propylene carbonate, which makes up for these disadvantages.
According to the invention, the process to improve the reversibility of the insertion of lithium in a carbon electrode of a lithium ion secondary electrochemical generator, using an electrolyte comprising propylene carbonate, consists of forming electrochemically, during the first use of the generator, a passivation film on the surface of the carbon electrode essentially using an organic compound selected from the cyclic and non-cyclic xcex1-halogenated esters.
These organic compounds are of particular interest since they make it possible to form a passivating coat on the carbon electrode, during the first use of the electrochemical generator, while being used in a much lower quantity than that required in the case of chloroethylene carbonate used in reference [4].
According to the invention, a xcex1-halogenated ester that is liquid at ambient temperature or soluble in propylene carbonate PC or in a mixture of PC and other solvents, and is also stable under the operating conditions of the electrochemical generator, is selected.
The halogen used in the ester may particularly be chlorine, bromine or iodine.
Examples of such non-cyclic xcex1-halogenated esters include alkyl halogen formiates and halogen acetates, particularly alkyl chloroformiates and chloroacetates.
Chloroformiates comply with the formula ClCOOR where R represents a linear or ramified alkyl group, preferably a lower alkyl group, with one to four carbon atoms such as the methyl or ethyl groups. In particular, it is possible to use methyl chloroformiate.
Alkyl chloroacetates comply with the formula ClCH2-COOR where R has the same significance as above.
Other non-cyclic esters liable to be used may comply with the formula R-CHCl-COOR where the Rs may be the same or different, with the same significance as above.
According to the invention, it is also possible to use cyclic xcex1-halogenated esters complying with the following formula, for example:
wherein X represents a halogen such as Cl, Br or I, and n is a whole number ranging from 1 to 3, it being possible to replace one or more of the CH2 groups by methyl, ethyl, propyl or butyl groups.
An example of a cyclic ester of this type is xcex1-bromo-xcex3-butyrolactone BrBL which complies with formula (II) given above, where n=2 and X represents Br.
According to a preferred embodiment of the invention, the organic compound selected from the cyclic and non-cyclic xcex1-halogenated esters is added to the electrolyte of the electrochemical generator, so as to enable the formation of the passivation film on the surface of the electrode during the first use of the generator.
According to a second embodiment of the invention, the organic compound selected from the cyclic and non-cyclic xcex1-halogenated esters, is adsorbed on the carbon electrode. In this case, the electrode is first of all subjected to an organic compound adsorption step by immersing it in said compound, before using it in the electrochemical generator. As described above for the first use, a passivation film on the carbon electrode is formed from the adsorbed compound by electrochemical reduction.
In the first embodiment of the invention, the electrolyte advantageously comprises a solution of at least one lithium salt in a solvent composed of a mixture comprising propylene carbonate and the organic compound selected from the cyclic and non-cyclic xcex1-halogenated esters.
The lithium salt(s) used may be selected from the salt generally used in lithium ion electrochemical generators. Lithium perchlorate LiClO4, lithium hexaf luoroarseniate LiAsF6, lithium hexaf luorophosphate LiPF6, lithium tetrafluoroborate LiBF4, lithium trifluoromethanesulfonate (lithium triflate) CF3SO3Li and lithium trifluorosulfonylimide (LiTFSI) LiN(CF3SO2)2 are preferably used.
In an electrolyte of this type, the added organic compound content may be low. It is selected so as to form a passivation film with a sufficient thickness over the entire surface of the electrode to prevent contact between the propylene carbonate molecules and the carbon electrode, but this proportion must not be excessively high since, if the film is too thick, it will prevent the diffusion of the lithium ions in the electrode.
When xcex1-bromo-xcex3-butyrolactone is used as the added organic compound, it may represent 0.5 to 3% by volume of the solvent composed of the mixture of propylene carbonate and xcex1-bromo-xcex3-butyrolactone, and preferably 1 to 2% by volume of the solvent.
The lithium salt concentrations of the electrolyte according to the invention are generally such that the electrolyte contains at least 0.1 mol/l of lithium ions. For example, the lithium salt concentration may be within the range from 0.1 mol/l to saturation.
In the lithium ion electrochemical generator using such an electrolyte and a carbon electrode, the other electrode, or positive electrode, may be made of various materials such as oxides, sulphides or oxysulphides.
Examples of oxides that may be used include vanadium oxide V2O5, nickel oxide NiO2, cobalt oxide CoO2, mixed. cobalt and nickel oxides, manganese oxides, molybdenum oxide MoO3, chromium oxides and vanadium bronzes MxV2O5, where M represents iron, sodium, potassium, lithium, silver, aluminium, chromium, barium, nickel or cobalt.
Examples of sulphides that can be used include titanium sulphide TiS2, molybdenum sulphide MoS2 and mixed nickel and molybdenum sulphides.
Examples of oxysulphides that can be used include molybdenum and titanium oxysulphides.
In an electrochemical generator of this type, using an electrolyte according to the invention, a separator is generally placed between the electrodes and said separator may be composed of a microporous film made of polypropylene or polyethylene, for example.
The generator. may be produced in, the form of a cylindrical generator comprising a spiral winding of the two electrodes separated by the separator if required. It may also be produced in the form of a prismatic type generator with plane electrodes facing each other and possibly a separator placed between these electrodes.
Other characteristics and advantages of the invention will be seen more clearly upon reading the following description, which is naturally given as a non-restrictive illustration with reference to the appended drawings.

Additives for improving the reversibility of a carbon electrode of a lithium ion secondary electrochemical generator


An electrical amplifier comprising an output stage that can be supplied by an electrical energy source, is connected to a control device on the input side, the control signal of the control device controlling an output signal of the output stage dependent on a parameter value of the energy source. The amplifier is has a compensation device that is connected to the energy source and the control device, and is used to modify the control signal according to the parameter value of the energy source which can be, for example, the network voltage of the energy source. A method for controlling an electrical amplifier comprising an output stage supplied by an electrical energy source includes, determining parameter value of the energy source, deriving a compensation signal therefrom, and a control signal for the output stage is generated according to the compensation signal. The amplifier and method can be used in a gradient amplifier for a magnetic resonance appliance.

Often, electrical amplifiers have a two-stage construction. In a first stage, an intermediate circuit generator or a power supply unit generates a supply voltage of medium amplitude or precision. The supply voltage and intermediate circuit generator supply an output stage for generating an output signal with the desired properties. Depending on requirements, the output signal may have a voltage that is transformed upward compared to the supply voltage and, may have predeterminable constant or time-dependent signal properties. For use as a gradient amplifier for gradient coils in magnetic resonance systems, especially fast-time dependent output signal properties that must be adhered to precisely must be assured.
The precision with which the desired parameter values of the output signal, such as current or voltage, can be adhered to depends, among other factors, on fluctuations in the power supply voltage. Under some circumstances, fluctuations in the power supply voltage can be partly compensated for by circuitry of the output stage. However, complete compensation is not always possible, and hence not all the requirements made of the output signal can readily be met.
With a view to the quality of the output signal, a stabilized power supply unit is employed. In addition, the desired parameters of the output signal can be regulated, and the regulator, for instance, regulates switching times of switch elements of the output stage. Such regulation can be adapted optimally to the desired mode of operation of the output stage, so as to minimize the effects of a fluctuating supply voltage. Nevertheless, at critical operating points, for instance when the time-dependent properties of the output signal are changing rapidly, an influence of the power supply signal remains. Depending on the output signal requirements, additional compensation for supply fluctuations can therefore be desirable.

Amplifier having a regulation system controlled by the output stage


In one embodiment, a biased fabric is supplied. The biased fabric supply has a first specified width and a first bias angle of warp yarns relative to weft yarns. At least one overfeed roller configured to overfeed fabric from the biased fabric supply at an overfeed rate is provided. At least one spreading arm configured to stretch the fabric to a second specified width and a fabric oven configured to heat the biased fabric supply to a specified temperature and output a balanced crimp and/or elongation biased fabric are also provided.

Rubber or other elastomeric belts can be reinforced with fabric, including fabric having thermoplastic fibers. As noted in U.S. Pat. No. 5,068,000 to Lauderdale ("Lauderdale"), which is incorporated herein by reference in its entirety, such reinforcing fabric can be incorporated into or upon elastomeric materials of a belt to improve the stability of the belt. Warp and weft yarns of reinforcing fabric incorporated into a belt can be oriented at an angle such as sixty degrees relative to the longitudinal direction of axis of a belt. Therefore, biased fabric can be employed for such an application.
Fibers or yarns of such biased fabric that are oriented in the warp direction may posses a different elongation and/or crimp relative to fibers or yarns oriented in the weft direction. The varying degree of elongation and/or crimp can be a result of prior art systems and methods employed in fabricating biased fabric for the purposes of reinforcement of elastomeric belts.

Systems and methods for fabricating biased fabric


The invention is a coating composition containing an aqueous polyurethane dispersion wherein the polyurethane is prepared from a mixture of polycaprolactone diols and an isocyanate mixture having an NCO functionality of more than 1.5 wherein the ratio NCO:OH is from 0.9:1 to 2.5:1. The polyurethane also can contains functional components capable of salt formation in the aqueous solution. The coating composition is particularly useful for coating flexible substrates such as leather and flexible polymeric materials.

Coating compositions based on aqueous polyurethane dispersions have been known for some time. In general, the polyurethanes on which the polyurethane dispersions are based are produced by polyaddition of polyols with diisocyanates, the co-condensation of components capable of salt formation having an advantageous effect on dispersibility. Polyurethane urea dispersions, which are also used as coating compositions, are formed in the presence of chain-extending agents, such as diamines.


A magnetic filter carriage (16) for use in filtering contaminants from fluid in a high pressure fluid flow comprises a frame (18, 20, 22) arranged to support a plurality of magnet filter rods (42), such that the rods (42) are each supported at both ends thereof in a fixed orientation, for example parallel to one another. The frame (18, 20, 22) is adapted to be inserted within a pressure vessel (4) across the direction of fluid flow between a fluid inlet (7) and a fluid outlet (9) of the pressure vessel (4), and may be arranged such that more than about 90% of the flow across the vessel (4) passes through the frame (18, 20, 22). The rods (42) are mounted in a plurality of cassettes (36) which are easily removable for cleaning or replacement.

Fuel filters are well known in the art and usually take the form of in line filtering materials, such as a paper, mesh, fibrous or woven filter cartridges. The fuel is passed through the filter material such that any contaminant particles are collected on the upstream surface of the material. A problem with these filters is that they have to be removed and either cleaned or replaced periodically in order to remove the contaminants which gradually block the filter material. Furthermore the pressure differential across the filter builds up as the filter becomes dirty, requiring more energy to pump the fuel through the filter. The magnitude of the pressure differential is an indication of the state of the filter, and therefore can be used to ascertain when the filter should be removed and replaced. This system of filtering is costly in terms of replacement costs and energy costs.
Magnetic filters are known, for example for use in domestic heating systems. A magnet rod is inserted in a thin walled tubular housing extending into the pressure vessel. The magnets attract debris in the fluid, in particular magnetic iron and steel particles such as rust, which collects around the tube. The system will need cleaning when sufficient debris has built up to form a barrier between the magnets and the fluid, which reduces the efficiency of rust collection due to the radial distance of the new material being collected from the magnetic core. This can be determined by visual inspection. However such a filter is not suitable for high pressure environments such as fuel pipelines, since it would be necessary for the tube to withstand a very high pressure differential between the fuel in the vessel and atmosphere. Furthermore it is difficult to determine when the filter is clogged since visual inspection would require the system to be drained.
Magnetic filters have been proposed fore use in pipelines comprising a pipe section of increased diameter, with a large aperture formed in the pipe wall for receiving a magnet filter unit. The unit comprises a plurality of filter rods extending parallel to each other and connected at one end to an end plate for fitting into and securing around the aperture. A disadvantage of this arrangement is that 'dead' zones exist around the rods, commonly amounting to around 30% of the cross-sectional area of the pipe. Also, such a system is not practical for use in large or high pressure pipelines, or those carrying hazardous fluids, since the unit would be extremely heavy and cumbersome to manipulate due to the need to remove a large pressure containing flange with multiple magnetic rods, and the requirements for sealing around the end plate would be extremely difficult to achieve. It has therefore been difficult to use magnetic filters for fuel pipelines. The present invention aims to alleviate some or all of these problems.


A cable connector comprises a housing, a signal conductive contact having a first transformable portion for holding a core conductor of a coaxial cable in a condition of caulking connection, a ground conductive contact having a second transformable portion for holding an outer conductor of the coaxial cable in a condition of caulking connection, and a cover member for engaging with the housing to cover the first transformable portion of the signal conductive contact and the second transformable portion of the ground conductive contact and operating to transform the first transforming portion of the signal conductive contact so as to hold the core conductor of the coaxial cable in the condition of caulking connection and to transform also the second transforming portion of the ground conductive contact so as to hold the outer conductor of the coaxial cable in the condition of caulking connection.

1. Field of the Invention
The present invention relates generally to a cable connector and a method of connecting a cable with a cable connector, and more particularly to an improvement in a cable connector which has signal and ground conductive contacts isolated from each other to be connected respectively with core and outer conductors of a coaxial cable, and an improvement in a method of connecting electrically a coaxial cable having core and outer conductors with a cable connector having signal and ground conductive contacts isolated from each other to be connected respectively with the core and outer conductors of the coaxial cable.
2. Description of the Prior Art
There has been proposed to use often a cable connector with which a coaxial cable, which comprises a core conductor, an outer conductor surrounding the core conductor, an insulating layer provided between the core conductor and the outer conductor and an insulating cover surrounding the outer conductor to form a signal transmitting path unsusceptible to influence of noise, is electrically connected, when electrical parts, electrical devices or electrical apparatus are connected with each other through the coaxial cable so that signal transmissions are carried out through the coaxial cable between the electrical parts, electrical devices or electrical apparatus. The cable connector thus used is provided, for example, with signal and ground conductive contacts isolated from each other, with which the core and outer conductors of the coaxial cable are connected respectively.
In a previously proposed cable connector for a coaxial cable, it is usual to use soldering for connecting electrically the coaxial cable with the cable connector. That is, when the coaxial cable is connected electrically with the cable connector, a core conductor of the coaxial cable is soldered to a signal conductive contact of the cable connector and an outer conductor of the coaxial cable is also soldered to a ground conductive contact of the cable connector.
In the case of the soldering for connecting electrically the coaxial cable with the cable connector, in which the core and outer conductors of the coaxial cable are soldered respectively to the signal and ground conductive contacts of the cable connector, there is a problem that operations for soldering the core and outer conductors of the coaxial cable respectively to the signal and ground conductive contacts of the cable connector are troublesome for an operator or that heat accompanying with the soldering spreads through the coaxial cable to bring about inconveniences. Such a problem is severe especially when a slender coaxial cable having a relatively small diameter is connected electrically with the cable connector or a cable aggregate constituted with a plurality of coaxial cables arranged in parallel with one another to be flat is connected electrically with the cable connector.
Accordingly, it has been desired that a cable connector with which the coaxial cable is connected electrically without using soldering is provided. As for the cable connector with which the coaxial cable is connected electrically without using soldering, there has been previously proposed a cable connector in which the core and outer conductors of the coaxial cable are connected respectively with the signal and ground conductive contacts of the cable connector by means of press-contacting, as disclosed in, for example, the Japanese patent application published before examination under publication number 2001-223039.
In the previously proposed cable connector disclosed in the publication mentioned above, a plurality of signal conductive contacts and a plurality of ground conductive contacts supported by a contact supporting plate member are provided in such a manner that each of the signal and ground conductive contacts is provided with a U-shaped connecting portion at the end thereof or the signal conductive contact is provided with a U-shaped connecting portion at the end thereof and the ground conductive contact is coupled with a pair of catching plates. Then, the coaxial cable is connected electrically with the previously proposed cable connector in such a manner that the core conductor of the coaxial cable is pushed in the U-shaped connecting portion of the signal conductive contact of the cable connector and the outer conductor of the coaxial cable is pushed in the U-shaped connecting portion of the ground conductive contact of the cable connector or the core conductor of the coaxial cable is pushed in the U-shaped connecting portion of the signal conductive contact of the cable connector and the outer conductor of the coaxial cable is put between the catching plates with which the ground conductive contact of the cable connector is coupled. Thereby, the coaxial cable is connected electrically with the cable connector without using soldering in such a manner that the core conductor of the coaxial cable is in press-contact with the U-shaped connecting portion of the signal conductive contact of the cable connector and the outer conductor of the coaxial cable is also in press-contact with the U-shaped connecting portion of the ground conductive contact of the cable connector or the core conductor of the coaxial cable is in press-contact with the U-shaped connecting portion of the signal conductive contact of the cable connector and the outer conductor of the coaxial cable is press-contact with the catching plates with which the ground conductive contact of the cable connector is coupled.
In the above-mentioned previously proposed cable connector in which the core and outer conductors of the coaxial cable are connected respectively with the signal and ground conductive contacts by means of press-contacting, the core conductor of the coaxial cable is connected with the signal conductive contact by pushing the core conductor in the U-shaped portion of the signal conductive contact to come into press-contact with the same and the outer conductor of the coaxial cable is connected with the ground conductive contact by pushing the outer conductor in the U-shaped portion of the ground conductive contact or by putting the outer conductor between the catching plates with which the ground conductive contact is coupled to come into press-contact with the U-shaped portion of the ground conductive contact or the catching plates. In the case that the core conductor of the coaxial cable is connected with the signal conductive contact of the cable connector only by means of press-contacting the core conductor with the U-shaped portion of the signal conductive contact and the outer conductor of the coaxial cable is connected with the ground conductive contact of the cable connector only by means of press-contacting the outer conductor with the U-shaped portion of the ground conductive contact or press-contacting the outer conductor with the catching plates with which the ground conductive contact is coupled, as mentioned above, there is a problem that the connection of the core conductor of the coaxial cable with the signal conductive contact of the cable connector or the connection of the outer conductor of the coaxial cable with the ground conductive contact of the cable connector is lacking in certainty.
For example, it is feared that the core conductor of the coaxial cable is not pushed enough in the U-shaped portion of the signal conductive contact of the cable connector so as to be lifted out of the U-shaped portion of the signal conductive contact and thereby the core conductor of the coaxial cable is uncertainly in press-contact with the U-shaped portion of the signal conductive contact, or the core conductor of the coaxial cable is pushed excessively in the U-shaped portion of the signal conductive contact of the cable connector so as to be partially cut off and thereby the core conductor of the coaxial cable is uncertainly in press-contact with the U-shaped portion of the signal conductive contact. Further, it is further feared that the outer conductor of the coaxial cable is not pushed enough in the U-shaped portion of the ground conductive contact of the cable connector also so as to be lifted out of the U-shaped portion of the ground conductive contact and thereby the outer conductor of the coaxial cable is uncertainly in press-contact with the U-shaped portion of the ground conductive contact. Especially, when an extremely slender coaxial cable having, for example, the diameter of a core conductor of 0.075 mm, the outer diameter of an insulating layer surrounding the core conductor of 0.2 mm, the outer diameter of an outer conductor of 0.26 mm and the outer diameter of an insulating cover surrounding the outer conductor of 0.34 mm is connected electrically with the cable connector by means of press-contacting, it is seriously feared that the extremely slender coaxial cable is partially cut off on the cable connector.

Cable connector and method of connecting a cable with a cable connector


An image pickup apparatus capable of, when adjusting the white balance in development processing, eliminating the need for performing integration processing and calculation processing for white balance adjustment even when white balance is set to an arbitrary mode, thereby significantly reducing the processing time. In the image pickup apparatus, a calculation unit is adapted to, in a case where an integration parameter to be set in an integration unit is identical with or close to an integration parameter stored in a storage unit, calculate a white balance control value using a white balance integration value read out from the storage unit, without performing calculation processing using a white balance integration value acquired by an integration unit.

1. Field of the Invention
The present invention relates to an image pickup apparatus having a plurality of white balance modes, and a white balance control method thereof, and a storage medium.
2. Description of the Related Art
Digital cameras are conventionally known which is capable of outputting a video signal of the digital camera as it is (see Japanese Laid-Open Patent Publication (Kokai) No. 11-261933 and Japanese Laid-Open Patent Publication (Kokai) No. 2001-223979). Utilizing image data of a video signal as it is (hereunder, referred to as "the raw data") is utilized enables image correction processing to be expected after photographing.
Since the raw data is image data of a video signal as it is, the raw data can be converted into commonly handled image data such as JPEG format data by performing image processing (hereunder, referred to as "the development") on the raw data. A function of adjusting the white balance is one kind of image correction processing for the raw data. With this function, it is possible to switch a white balance mode after photographing to obtain image data having the appropriate color tones.
Technology is also known of improving the accuracy of white balance adjustment when a white balance mode is switched by storing information that shows a shift in a blackbody locus in the raw data (see Japanese Laid-Open Patent Publication (Kokai) No. 2003-324746).
However, there is the following problem with the conventional image pickup apparatus described above. That is, when setting a white balance (WB) mode to perform correction processing for color tones, it is necessary to perform integration processing for video signals included in the raw data and also perform WB calculation processing utilizing an integration value that is obtained by the integration processing.
Conventionally, when performing this processing and switching among a plurality of white balance settings to view changes in color tones, there is a problem that it is necessary to execute the aforementioned integration processing and calculation processing for each white balance mode, to require substantial processing time.
Further, the amount of data in video signals is increasing because of the increasing numbers of pixels in images captured by image pickup devices in recent years. As a result, the processing times required for integration processing and calculation processing are steadily increasing.
Furthermore, with respect to image pickup apparatuses having a function of capturing an image as the raw data, when image data subjected to the development processing at the image pickup apparatus main unit is compared with image data obtained after subjecting the raw data to the development processing on a PC or the like after photographing, the processing and the results relating to white balance adjustment are not the same. As a result, there is a problem that the color reproduction properties deteriorate.

Image pickup apparatus, white balance control method thereof, and storage medium