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|Blog Posts
Most of the time, if not all the time, the food I prepare in my house does not lend itself well to the addition of artificial flavours and colours in order to create an impression. Most (again, if not all) of the time, my food, though simple and unpretentious, is highly aromatic and colourful, at any rate. This is the first year that I have felt 'obliged' to take a more liberal approach to food preparation. But it did not detract me from seeking out more natural approaches to icing cupcakes. And all because the artificial stuff simply doesn't exist on our supermarket shelves.
Another problem I found with making frosting is the high cost of butter in Hania. Forget the locally produced stuff; it smells like a sheep station (we don't have locally made cow's butter). Good quality butter is very expensive in a non-producing region like Crete. From experience, I've found that most recipes which call for butter can be made with olive oil instead. I decided to replace the butter with olive oil, which flows like water in our house. I don't expect my readers to take up this idea (unless they live in Crete or have ample supplies of olive oil). It did turn out to be successful though!
I started off by beating a mixture of olive oil and icing (confectioner's) sugar. The pale yellow mixture (I could not get a white colour) came out very smooth and glossy, able to hold stiff peaks - but it tasted of olive oil. I added some vanilla sugar to mask the taste, but that wasn't enough; the taste improved when I added a very small amount of peach jam (it did not affect the colour). By adding cocoa powder to the same mixture, I got a classic chocolate (ie brown) icing. The icing was easy to apply on a cupcake (the one above was made with frozen grated summer zucchini). It even gave good results when used in a piping tube. My main worry was that it would melt if left out at room temperature for a long time - but it didn't. The icing remained set, it did not run, it didn't go crusty in the fridge, and, above all, it tasted good.
The results of my experimentations with natural colours and flavours were all conducted during a test session with my children in my kitchen. They tasted everything and I adjusted the ingredients accordingly. My first test session looked into achieving good texture, while my second session looked into natural colourings, which necessitated adding the dimension of taste when I added natural ingredients.
Brown (chocolate flavour with cocoa powder), dark pink (strawberry jam flavour with beetroot dye), creamy white (peach jam flavour) and light pink (dried crushed blueberry flavour - I was hoping for a blue-purple tinge, but this didn't work). You will see some olive oil floating on the top of some icings; as I added liquids to adjust colour and taste, I found that the oil began to separate from the mixture. This was able to be drained away completely and it did not affect the taste or texture of the icing. In fact, the removal of the excess oil improved both taste and texture.
The cream and brown coloured icing didn't present any problems, which encouraged me to continue with my experiments. The pink icing was achieved with a drop of strained beetroot liquid and some strawberry jam to mask the taste of the vegetables (strawberry jam alone was not enough to colour my frosting).
With the help of a piping set, my daughter decorated the beetroot-walnut-cocoa cupcakes above; my creations are below. My natural icing colours reminded me of the colours found in the sepia tones of old-fashioned photography. They were all able to be used with a piping tube, and they set without running.
For a white coloured icing, I made some simple glaze using icing sugar mixed with water, which I later discovered could be substituted with lemon juice for a tangy flavour. Orange juice also makes a tasty pale yellow-orange glaze, but don't expect a bright orange colour!
The white icing was dense enough to set without running; by the time I made the 'orange' icing, I had run out of sugar!
Green is a difficult colour: would avocado (with lemon juice) work? How about nettles, which give a deep green colour? But what about the taste? Sometimes, it's just so much more convenient to use the easy option...
*I finally found a packet of food colours containing three vials of red, blue and yellow food colouring at a larger brnach of Carrefour at a cost of 2.40 euro.
©All Rights Reserved/Organically cooked. No part of this blog may be reproduced and/or copied by any means without prior consent from Maria Verivaki.
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Worst ever Internet censorship law planned for South Africa - MyBroadband
The Draft Online Regulation Policy recently issued by the Film and Publication Board (FPB) of South Africa is such a regulation. It's as if the fabled prude Mrs. Grundy had been brought forward from the 18th century, stumbled across hustler.com on her ...
Municipal Demarcation Board
The Municipal Demarcation Board provides municipal boundary information and maps, and details about the demarcation process.
Web: http://www.demarcation.org.za/
Location: South Africa
Desc: Municipal Demarcation Board
Welcome to the Municipal Demarcation Board - South Africa
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Metropolitan, District, Local, Traditional, Local Authority, Municipal Powers, Municipal Functions, Wards, Demarcation Maps, Local Government, Elections, Delimitation, Municipal, South Africa, Statistics, Demographics, Contact, Councillors, Sa Explorer, Municipal Profile

subset: commoncrawl


text:
Looking back in the 25 years since CU Times first published, how have the industry's trade associations changed?
RBC2 still threatens credit unions, and trade associations' divided approach may have its own consequences.
Of the 250 issuers that have Apple Pay agreements, approximately 155 are credit unions.
Reflecting on Larry Sharp's credit union legacy.
Stephanie Smith was named the executive director for America's Credit Union Museum in Manchester, N.H., the organization's board of directors announced. She replaced Peggy Powell who retired after 15 years of service. Smith most recently served as director of alumni & development events at St. Paul's School, an international preparatory...
Strong internal controls are just one source of prevention.
Thanks for the Oct. 15 article, "Firms Circle Credit Unions in Growing Core Space." I agree that among our peer credit unions, core conversion is the main item on the business plan. SAFE Credit Union will begin our search process this year and convert during the two-year period following our...
Anthony Silvi was appointed SVP and chief lending officer for the $592 million Sb1 Federal Credit Union in Philadelphia. Previously, he served as the vice president of financial services at the $656 million Freedom Credit Union in Warminster, Pa. He also worked as SVP of lending at First Penn Bank...
Credit unions say NCUA examiners are pressuring them to keep long-term fixed assets below 35% of total assets, sacrificing income.
Pressured by NCUA examiners and concerned about interest rate risk, credit unions shed mortgages and other fixed rate assets, giving up income.


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Georgia Yellow Hammers
The Georgia Yellow Hammers is an old-time string and vocal quartet from Gordon County, Georgia from the 1920s. The group featured Charles Moody, Jr. on guitar; Bud Landress on banjo; Phil Reeve on guitar; and Bill Chitwood on fiddle.[1]
Collaboration with the Baxters[edit]
The group often played with Andrew and Jim Baxter from Curryville, GA (also in Gordon County). Curryville was also home to music legend Roland Hayes. Andrew Baxter's unique style of fiddle is heard an early recording of a band favorite entitled "G-Rag". Interestingly enough, the Baxter's were African Americans. This is an interesting note due to the time period. The band released one of the top selling records of 1920s southern music with 1927's release "The Picture on the Wall"/"My Carolina Girl".[1] The 1927 recording session with the Baxter's took place in Charlotte, NC, and was a rare integrated session, uncommon even through the mid to late 20th century.[2] Andrew and Jim Baxter were a well known duo for the time in their own right around Northwest Georgia.
The band is nationally recognized as an important 1920s "old-time" band. Their songs can still be heard from early recordings on such sites as YouTube.com and others. The song "Drifting Too Far From The Shore" written by member Charles Moody has been covered by such artists as Jerry Garcia,[3] Emmylou Harris, Phil Lesh & Friends, Hank Williams, and many others, as well as being a standard in many gospel hymnals. The Calhoun High School football stadium in Calhoun, Georgia is also named after the guitar player and founding member Phil Reeve.
Georgia Yellow Hammers recorded songs including:
Mary, Don't You Weep[4]
I'm S-A-V-E-D[5]
Pass around the Bottle[6]
Fourth of July at a County Fair (1927)[7]
Going to Ride That Midnight Train[8]
Tennessee Coon (1927)[9]
My Carolina Girl (1927)[10]
G Rag with Andrew Baxter (1927 Aug. 9)[11]
Peaches down in Georgia[12]
Picture on the Wall (1928)[12]
Further reading[edit]
- Wayne W. Daniel, Pickin' on Peachtree: A History of Country Music in Atlanta, Georgia (Urbana: University of Illinois Press, 1990), 76-77.
- The Encyclopedia of Country Music, ed. Paul Kingsbury (New York: Oxford University Press, 1998), s.v. "Georgia Yellow Hammers."
- Gene Wiggins and Tony Russell, "Hell Broke Loose in Gordon County, Georgia," Old Time Music 25 (summer 1977): 9-21.
- Charles K. Wolfe, "The Georgia Yellow Hammers," in Classic Country: Legends of Country Music (New York: Routledge, 2001).
- Tony Russell, Old Time Music Journal
- ^ a b "New Georgia Encyclopedia: Georgia Yellow Hammers". Georgiaencyclopedia.org. 2007-10-05. Retrieved 2013-03-05.
- ^ "Blogger: Aanmelden". Oldbluebus.blogspot.com. Retrieved 2013-03-05.
- ^ "The Jerry Site". The Jerry Site. Retrieved 2013-03-05.
- ^ "Georgia Yellow Hammers-Mary, Don't You Weep". YouTube. 2010-06-19. Retrieved 2013-03-05.
- ^ "The Georgia Yellow Hammers-I'm Saved". YouTube. 2010-02-26. Retrieved 2013-03-05.
- ^ "The Georgia Yellow Hammers-Pass Around The Bottle". YouTube. 2010-06-22. Retrieved 2013-03-05.
- ^ "Georgia Yellow Hammers : Fourth Of July At A County Fair ( 1927 )". YouTube. 2008-12-05. Retrieved 2013-03-05.
- ^ "The Georgia Yellow Hammers-Going To Ride That Midnight Train". YouTube. 2010-07-10. Retrieved 2013-03-05.
- ^ "Georgia Yellow Hammers, Tennessee Coon. North Carolina 1927.". YouTube. 2011-09-09. Retrieved 2013-03-05.
- ^ "The Georgia Yellow Hammers-My Carolina Girl". YouTube. 2010-08-24. Retrieved 2013-03-05.
- ^ "Andrew Baxter with the Georgia Yellow Hammers G Rag VICTOR 21195". YouTube. 2011-09-03. Retrieved 2013-03-05.
- ^ a b "The Georgia Yellow Hammers-The Picture On The Wall". YouTube. 2010-07-27. Retrieved 2013-03-05.


text:
Muramasa trades in its console counterpart for a sleeker, more compact platform.
Tag Archive: the demon blade
Muramasa: Rebirth review for PS Vita
July 9th, 2013
by Aaron Vaughn
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Amy M.
Original recipe yields 4 servings
Amount per serving ({{servings}} total)
Based on a 2,000 calorie diet
Ready In
Wow!!! That is all I can say! WOW WOW WOW WOW WOW!!! This is soooo awesome!! I didn't have the sherbert but it is still awesome!!
This "smoothie" was great! I did not have any strawberry sorbet so I used about 1/2 cup of plain yogurt and about 1/2 cups of peach juice since that is what I had on hand. I transfomed this sm...


text: Exit this survey Best of Bethel 2013-14 Introduced in Sunday River's free newspaper, Sunday River This Winter, the Best of Bethel invites you to celebrate the Bethel region with us. We're now celebrating our third year of Best of Bethel and we still want to know your Happy Place, whether it's an early morning run on a favorite trail or a race to the pub at the end of the day for a well-deserved basket of fiery hot wings—now tell us. You have until January 18 to cast your ballot. Please only vote one time and use just the official name for your answer. We'll collect your answers and publish them in Sunday River This Week later in the season. Thanks for participating! 1. Best Breakfast 2. Best Cup o' Joe 3. Best Lunch Spot 4. Best Bar-Apres Ski 5. Best Bar-Late Night 6. Best Beer Selection 7. Best Martini 8. Best Bar Menu 9. Best Pizza 10. Best Wings 11. Best Nachos 12. Best Burger 13. Best Place To Splurge on a Meal 14. Best International Meal 15. Best Bartender--Please mention name and establishment 16. Best Waiter/Waitress--Please mention name and establishment 17. Best Food on the Run 18. Best Shop for Purchasing Locally Crafted Gifts 19. Best Photo Spot 20. Best First Run of the Day 21. Best Bump Run 22. Best Glade 23. Best Winter Hike 24. Best Spring Deck Scene 25. Best Annual Event 26. Best Live Music Venue 27. Best Use of Bacon 28. Best Chairlift at Sunday River 29. Best Summer Hike 30. Best Kids Activity I'm Happy with my answers. Vote now!


text:
McGee also among first-timers on ballot
Updated: November 30, 2004, 11:20 AM ETAssociated Press
NEW YORK -- Five-time AL batting champion Wade Boggs, eight-time All-Star Darryl Strawberry and two-time NL batting champion Willie McGee are among 12 players who will appear on the Hall of Fame ballot for the first time.
Ryne Sandberg, Bruce Sutter, Jim Rice, Andre Dawson and Rich Gossage head the returning players on the ballots, which will be mailed this week to eligible voters in the Baseball Writers' Association of America.
Also among the newcomers announced Monday ...
Read full story
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Originally written on Fox Sports Florida | Last updated 4/6/12
Washington Wizards Gilbert Arenas falls hard after committing a foul on the Miami Heat during the fourth quarter at the Verizon Center in Washington on November 4, 2009. The Heat defeated the Wizards 93-89. UPI/Alexis C. Glenn Photo via Newscom
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MIAMI Gilbert Arenas is averaging a microscopic 4.3 points, but he seems happier than most guys who are putting up 20 a night. At Friday mornings shootaround at AmericanAirlines Arena, the guard was all smiles as his Memphis Grizzlies prepared to face the Miami Heat. And why not? What he calls the worst period of his life is over. I call them the dark years, Arenas says of the period between December 2009 and December 2011. Whats funny is I dont remember them. When people ask me about those years, I just dont remember. I guess I just subconsciously blanked them all out Im just trying to have fun now. That gloomy period started when it was came to light Arenas had drawn guns in the locker room with guard Javaris Crittenton when the two were with the Washington Wizards in December 2009. Arenas ended up being suspended for the remainder of the season. From there, I just tried to forget about life, said Arenas, 30, a three-time All-Star who is now just a role player. He says the d...
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ELEMIS supporting Breast Cancer Care - When was the last time you checked?
Men's skin differs to woman's, which is why ELEMIS has developed a men's grooming programme
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Originally written on Project Spurs | Last updated 2/8/13
San Antonio Spurs shooting coach Chip Engelland has helped numerous Spurs players with their shooting over the years. Former Spur Steve Kerr has raved about Engelland and the proof is in the pudding with Spurs all-star guard Tony Parker, who transitioned from a one-dimensional point guard whose main weapon was penetrating and finishing in the paint. With Engelland's help, Parker has developed a consistent, reliable jumper that has been effective off screens and has extended his range out to the three-point line. Now Engelland is helping another European import, Nando De Colo. A video on De Colo's YouTube channel has him working pregame with Engelland from shooting spot-up outside jumpers around the floor to shooting off the dribble and working on his decision making to either pull up for the shoot or drive. De Colo's shot is hardly bad, but with the benefit of Engelland's tutelage, any improvement would be more than welcome.
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text:
Coquilles St. Jacques
|1⁄4 Cup (4 tbs)
|Chopped celery
|1⁄4 Cup (4 tbs)
|Canned sliced mushrooms
|4 Ounce, drained (1 Can)
|Green onions
|2 Medium, sliced
|Chopped green pepper
|2 Tablespoon
|All purpose flour
|2 Tablespoon
|1⁄2 Teaspoon
|1⁄8 Teaspoon
|Bay leaf
|Dry white wine
|1⁄2 Cup (8 tbs)
|Sea scallops
|1 Pound
|Chopped pimiento
|1 Tablespoon
|Light cream
|1⁄4 Cup (4 tbs)
|Egg yolk
|2 Tablespoon
|Dry bread crumbs
|2 Tablespoon
|Grated parmesan cheese
|2 Tablespoon
1. Combine butter, celery, mushrooms, onions and green pepper in 2-quart glass casserole.
2. Microwave on ROAST for 3 to 4 minutes or until onion is tender. Stir in flour, salt, pepper, bay leaf and wine; mix well. Add scallops and pimento.
3. Microwave on ROAST for 6 minutes. Stir and continue cooking on ROAST for 2 to 3 minutes or until thickened. Mix together in small bowl, cream and egg yolk; stir into scallop mixture.
4. Microwave on ROAST for 2 to 3 minutes or until piping hot. Remove bay leaf. Spoon into 4 natural shells or 1-cup glass serving dishes.
5. Sprinkle about 1 tablespoon Buttered Bread Crumbs on each serving. Microwave on REHEAT for 1 to 2 minutes or until heated through. Let stand, covered, 5 minutes before serving.
6. Buttered Bread Crumbs: Place 2 tablespoons butter in 1-cup glass measure.
7. Microwave on ROAST for 1 to 1 1/2 minutes or until melted. Stir in bread crumbs and Parmesan cheese.


text: http://forums.fedoraforum.org – Hello, I've VNC (with SSL) access to my server. The server certificate has been signed by CA maintained by provider of the server. When I try to connect via TigerVNC it first warns me with "Hostname (...) does not match any certificate, do you want to continue?" and then another warning about unknown certificate issuer. If I wish to continue I'm presented with login dialog. When I try to connect via Vinagre it just hangs. Well, the programs runs and responds to clicks but it just show black window. I've checked in netstat that it's connected to the server. It just does nothing. (HowTos)


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Lister House
|Place Details
|Place ID
|Registration Type
|State Heritage
|Place Name
|Lister House
|Place Classification
|Place Category
Health and Care Services
|Place Type
Medical offices
10 Providing health and welfare services / 10.1 Providing health services
|Register Entry Date
|79 Wickham Terrace
|Town / Suburb
|Post Code
|Cultural Heritage Significance
|Principal Period
of Significance
|1930, 1948 (fabric) 1920s-1950s (historical)
|Criterion A
|Lister House is important in demonstrating the interwar evolution of Wickham Terrace as an important medical specialist precinct in Brisbane, and is associated with the development of specialist medicine in Queensland
|Criterion D
|Lister House is an accomplished and intact building which is important in demonstrating the principal characteristics of a small-scale, purpose-built interwar medical office building, including in the restrained design the assertion of medical specialist prestige.
|Criterion E
|As one of a related group of classical facades, and in particular in association with adjacent Inchcolm [600170], Lister House with its mannered facade exhibits a strong contribution to the Wickham Terrace streetscape, which is valued by the community.
|Criterion H
|The building has a special association with Brisbane architect RC Nowland, as an example of his private sector work and the innovative Brisbane Clinic concept, which was modelled on the Mayo Clinic in the United States of America.
|This two-storeyed masonry building was constructed in 1930 as purpose-designed medical suites for Lister House Ltd, a group of medical practitioners. Lister House Ltd acquired the site from the Congregational Church in 1929, and commissioned Brisbane architect Raymond Clare Nowland to design a building which could function along the lines of the Mayo Clinic in the United States. The contractor for the project was J I Green & Co. Drs LJ Jarvis Nye, John Bostock and John Power used the American model to institute the first specialist group practice in Queensland, the Brisbane Clinic, characterised by new standards of investigation and treatment, group consultation, shared facilities, and a reading circle (until the 1950s). Lister House was one of a number of interwar medical office redevelopments along Wickham Terrace. These included Inchcolm (QHR 600170), Ballow Chambers (QHR 600164), Wickham House and Craigston (QHR 600165). Their construction constituted the second phase (the first being in the 1880s) of the Terrace's growth as a medical precinct, and was indicative of new directions toward specialist medicine in Queensland in the interwar years. In 1948 the building was extended to the rear with the addition of a second reception and stairwell area and six offices on each storey. Some renovation of the building was undertaken in the 1980s.
|Lister House is located towards the eastern end of Wickham Terrace, overlooking the city centre, within an area dominated by buildings accommodating medical and allied professions. It is a two-storeyed, brick building with basement. The main arched entrance is surrounded by rendered mouldings which match the heavy render quoining to the angles of the building. Above the doorway is displayed a crest which incorporates a lighted torch, the date (1930) and the motto Lux sanant (light heals). On each side of the entrance are ornate bronze lamps of florentine design and arched windows with exaggerated keystones. Three rectangular windows with prominent mouldings distinguish the upper level. A heavy rendered cornice with a tiled roof behind completes the building. Although built in two stages, the internal finish to the newer section mirrors that of the first. The interior features silky oak joinery, parquetry floors, rough plaster finish on the walls to picture-rail height, plaster ceilings and cornices employing a variety of decorative mouldings, and leadlighted fanlights above doorways and in the arches of the central corridor. There are two reception and stairwell areas in the building, with the front staircase featuring silky oak treads and wrought iron balustrading. The basement was designed specifically to accommodate an x-ray unit, and continues to be used for this purpose. Lister House continues as a specialist medical office building.
|Element Name
|Lister House
|Designer Name
Nowland, Raymond C
|Design Period
|1919 - 1930s Interwar period
|Builder Name
Green, JI & Son
|Construction Period
|1930 - 1948
|Construction Method
Load-bearing brick
|Fabric (Exterior Structure)
|Images and Maps
|Create a Web Map
Information about places in the Queensland Heritage Register is maintained by the Department of Environment and Heritage Protection (EHP) under the Queensland Heritage Act 1992. Information available here is only part of the full Register entry and should not be taken as an official entry. Absence does not mean a particular place is not in the Register.
Certified copies of the full entries in the Register are available for a fee.
You can also search the full Register for a fee to find out if a place or parcel of land is listed or otherwise affected by the Act.
Last updated: 15 March 2013


text:
Liposomal-encapsulated taxol or an antineoplastic derivative thereof or a mixture thereof is provided which is used to effect a therapeutically enhanced method of treating cancer, and which may be used advantageously in combination with hyperthermia. The liposomes confer enhanced stability and solubility to taxol or derivatives thereof.
1. A method of modulating multidrug resistance in cancer cells in a mammalian host, comprising administering to said host a pharmaceutical composition comprising:
(i) a therapeutically effective number of liposomes comprising a liposome-forming material, cardiolipin, and an agent selected from the group consisting of taxol, an antineoplastic derivative of taxol, or a mixture thereof; and
(ii) a pharmaceutically acceptable excipient.
2. The method of claim 1, wherein said mammalian host is a human.
3. The method of claim 1, wherein said pharmaceutical composition further comprises a chemotherapeutic agent other than taxol or an antineoplastic derivative of taxol.
4. The method of claim 3, wherein said chemotherapeutic agent is an anthracycline glycoside.
5. The method of claim 1, wherein said antineoplastic derivative of taxol is taxotere.
6. The method of claim 1, wherein said liposome-forming material is at least one of the lipids selected from the group consisting of phosphatidyl choline, cholesterol, dipalmitoyl phosphatidyl choline and phosphatidyl serine.
7. The method of claim 1, wherein said cardiolipin is selected from the group consisting of natural cardiolipin and synthetic cardiolipin.
8. The method of claim 1, wherein said liposome bears a negative charge.
9. The method of claim 1, wherein said liposome bears a positive charge.
10. The method of claim 1, wherein said liposome is neutral.
11. The method of claim 1, wherein said liposomes are a mixture of multilamellar vesicles and unilamellar vesicles.
This application is a division Ser. No. 08/136,090 filed Oct. 14, 1993 now U.S. Pat. No. 5,424,073 which is a continuation Ser. No. 07/855,667, filed Mar. 23, 1992 now abandoned.
1. Field of the Invention
The present invention relates to liposome encapsulated taxol and a method of using the same.
2. Description of the Background Taxol, which is (2aR-(2aα, 4aβ, 6β, 9α(αR*, βS*), 11α, 12α, 12aα, 12bα))-β-(β-(benzoylamino)-α-hydroxybenzenepropanoic acid 6, 12b-bis(acetyloxy)-12-(benzoyloxy)-2a, 3, 4, 4a, 5, 6, 9, 10, 11, 12, 12a, 12b-dodecahydro-4, 11-dihydroxy-4a, 8, 13, 13-tetramethyl-5-oxo-7, 11-methano-14-cyclodeca (3, 4) benz (1, 2-6) oxet-9-yl ester, has the formula (I): ##STR1## Taxol was first isolated from the bark of the Pacific yew tree, Taxus breviofolia Taxaceae and has been shown to exhibit significant antineoplastic activity against the intraperitoneally (i.p.) implanted B16 melanoma, L1210 leukemia, P388 leukemia and the human MX-1 mammary tumor xenograft. More recently, it was determined that taxol exhibits tumor shrinkage in 30 to 40% of women with advanced ovarian tumors. Taxol has also shown considerable promise in the treatment of metastatic breast cancer.
Taxol inhibits normal cellular replication in vitro by promoting microtubule assembly and stabilizing tubulin polymers against depolymerization. Taxol functions as a mitotic spindle poison and is a potent inhibitor of cell replication in vitro. Taxol markedly enhances all aspects of tubulin polymerization, initiation and elongation are more rapid.
As noted in clinical trials, taxol has shown sufficient activity against lymphoma, ovarian and breast cancers.
Due to its limited solubility in water, taxol is prepared and administered in a vehicle containing cremophor EL, a polyoxyethylated castor oil, and ethanol in a 50:50 (vol/vol) ratio. This solution is further diluted 1:10 in saline before administration to humans. In clinical trials, a consistent problem of anaphylactoid reaction, dyspnea, hypertension and flushing have been encountered. The cardiac toxicity of taxol is treatment limiting and because of this the patient has to be hospitalized for continuous infusion of the drug.
In addition, the stability of taxol once diluted in saline solution is quite low. The drug degrades within 24 hours and hence handling of dosage for the patients becomes very difficult. In addition, the drug precipitates from dilution and hence an on-line filter is utilized for the infusion of drug to the patients.
Attempts to prevent taxol cardiotoxicity and anaphylactoid reaction have included reliance on pretreatment of patients with antihistamine and corticosteroids, and by prolonging the infusion time from six to twenty four hours. Even with these manipulations, patients suffer from serious toxicities which are often fatal.
Further, taxol has conventionally been obtained from Pacific yew trees in forests of the Pacific Northwest, requiring the sacrifice of about six trees to obtain a sufficient quantity of drug to treat one patient. Although it was recently announced that taxol could be produced synthetically, see The Wall Street Journal, Mar. 18, 1992, the yield is necessarily small due to the large number of steps involved in the synthesis.
Thus, even if improved syntheses of taxol could be devised, a number of drawbacks inherent in taxol use remain.
Thus, a need exists for a means by which the above drawbacks may be avoided or their impact minimized.
Accordingly, it is an object of the present invention to provide liposomal-encapsulated taxol, which minimizes the above drawbacks.
It is also an object of the present invention to provide a method for treating cancer in mammals.
Further, it is a particular object of the present invention to provide a method for treating lymphoma, breast, ovarian, lung and colon cancer in mammals.
Accordingly, the above objects and others are provided by liposomal-encapsulated taxol and antineoplastic derivatives thereof.
FIG. 1 illustrates the stability of liposomal taxol at different temperatures.
FIG. 2 illustrates a toxicity evaluation of free and liposomal taxol in normal mice.
FIG. 3 illustrates cytotoxicity of taxol on parent HL leukemia cells.
FIG. 4 illustrates taxol uptake by parent HL 60 cells.
FIG. 5 illustrates cytotoxicity of taxol on HL 60/VCR cells.
FIG. 6 illustrates taxol uptake by HL 60/VCR cells.
The present invention relates generally to liposome-encapsulated taxol and methods of using the same. Generally, any method of using taxol with a conventional therapeutic objective may be practiced in accordance with the present invention with surprisingly enhanced results.
In part, the present invention provides a delivery system for taxol to mammalian host which is characterized by 1) avoidance of solubility problems of taxol, 2) improved taxol stability, 3) avoidance of anaphylactoid reactions and cardiotoxicity, 4) ability to administer taxol as a bolus or short infusion rather than extended (24-hour) infusion of free taxol, 5) increased therapeutic efficacy of taxol, and 6) modulation of multidrug resistance in cancer cells.
As used herein, the term "liposome" means a closed structure composed of lipid bilayers surrounding an internal aqueous space.
Further, as used herein, the phrase "taxol as an antineoplastic derivative thereof" means taxol or any derivative of taxol which is or may be used in cancer chemotherapy due to its antineoplastic properties. It is particularly noted that although taxol is believed to function as an antineoplastic compound by promoting microtubule assembly and stabilizing tubulin polymers against depolymerization, the derivatives of the present invention are not limited to those which function by any particular mechanism.
For example, in addition to taxol, derivatives such as taxasm or others mentioned in synthesis and Anticancer Activity of Taxol derivatives D.G.I. Kingston et al, Studies in Organic Chemistry, volume 26, entitled "New Trends in Natural Products Chemistry"1986, Atta-ur-Rahman, P.W. le Quesue, Eds. (Elvesier, Amsterdam 1986), pp. 219-235 are explicitly included within the present invention. Further, the literature excerpt mentioned above is incorporated herein in the entirety.
Generally, in accordance with the present invention, taxol or a derivative thereof is dissolved in a suitable solvent. As a solvent, any non-polar or slightly polar solvent may be used, such as ethanol, methanol, chloroform or acetone. Then, cardiolipin is dissolved in a suitable solvent as described for taxol and the solutions are mixed.
Then, lipid-forming material is dissolved in a suitable solvent, which is generally a low polarity solvent such as chloroform, or a non-polar solvent, such as n-hexane the solvent mixture from above and the solution containing the lipid-forming material are mixed, and the solvents are removed to afford a thin, dry film of lipid and drug.
Liposomes are then formed by adding saline solution thereto. Thereafter, multi-lamellar liposomes may be formed by mixing the liposomes, for example, by vortexing.
Generally, the liposomes may be neutral, negative or positive liposomes. For example, positive liposomes may be formed from a solution containing phosphatidyl choline, cholesterol and staryl amine. Negative liposomes may be formed, for example, from solutions containing phosphatidyl choline, cholesterol and phosphatidyl serine.
Furthermore, is mixing the saline solution with the thin, dry film of lipid and drug, any form of dispersion may be used provided that it strongly homogenizes the mixture. For example, such homogenization may be effected by using a vortex, magnetic stirrer and/or sonication.
The cardiolipin used in accordance with the present invention may be obtained from either a natural or synthetic source as is known to those skilled in the art.
Having described the present invention, reference will now be made to certain examples which are provided solely for purposes of illustration and which are not intended to be limitative.
To 2.93 μM of taxol dissolved in chloroform 2.81 μM of cardiolipin in ethanol was added. To this mixture, 14.16 μM of phosphatidyl choline dissolved in hexane and 9.83 μM cholesterol in chloroform was added. The mixture was stirred gently and then solvents were evaporated under vacuum at below 30� C. A thin dry film of lipid and drug was formed. Liposomes were formed when 2.5 ml saline solution was added. The flasks were vortexed for 1/2 hour to provide multilamellar liposomes. These liposomes were then sonicated for 1/2 hour in a Heat System Cup horn sonicator which provided small unilamellar liposomes. The liposomes were then dialyzed against 1 liter saline solution for 24 hours. After the completion of dialysis, an aliquot of liposomes was dissolved in methanol and analyzed by high pressure liquid chromatography (HPLC). The encapsulation efficiency of taxol in liposomes was more than 95% of the initial input dose. The taxol concentration in these liposomes was 0.95 mg/ml.
In this preparation same experimental conditions were utilized except the quantities of drug and lipids were varied. For this preparation, the following concentrations were used: Taxol 5.86 μM, cardiolipin 5.62 μM, phosphatidyl choline 28.18 μM and cholesterol 19.38 μM. The solvents were then evaporated under vacuum and the dried lipids and drug layers were dispersed with 5 ml of 7% Trehalose-saline solution, hydrated, vortexed and sonicated. The liposomes were then dialyzed for 24 hours and the percent encapsulation of taxol in liposomes was more than 94% as assayed in HPLC.
To explore the potential use of taxol liposomes in hyperthermia, taxol was encapsulated in liposomes by using 2.58 μM of the drug, 15.26 μM of dipalmitoyl phosphatidyl choline and 8.79 μM cholesterol. The drug and lipid mixture was evaporated under vacuum and resuspended in 2.5 ml of saline. The remainder of the process was similar as described above. The taxol encapsulation efficiency was higher than 95%.
In this preparation of liposomes, cardiolipin was substituted with phosphatidyl serine to form taxol liposomes. In this case 2.11 μM taxol, 2.10 μM of phosphatidyl serine, 10.77 μM phosphatidyl choline and 7.24 μM cholesterol were used. The whole process was performed as described earlier and the liposomes were dialyzed extensively overnight and then the drug was assayed by HPLC. The percent encapsulation of taxol was found to be more than 95%.
The taxol liposomes were prepared as usual using cardiolipin, phosphatidyl choline and cholesterol. An aliquot of these liposomes was placed at room temperature, and refrigeration temperature (4� C.). As shown in the FIG. 1, the taxol liposomes at room temperature were stable for four days. On the contrary, the free taxol of 0.6 mg/ml concentration in saline degrades within 3 hours. The liposomal taxol at refrigeration temperature were stable for 1 month.
In another set of experiments, taxol liposomes were prepared in the usual way but instead of using saline, 7% trehalose-saline (a diglucose sugar) was used to resuspend the liposomes. Aliquots of these liposomes were placed at -20� C. and at -80� C. At -20� C., the taxol liposomes were also stable for 1 month as determined by HPLC. The experiment was terminated at this time. The liposomes with 7% trehalose were frozen at -80� C. for 5 months. Intermittently, the liposomes were thawed and frozen again. This process was repeated several times. At the end of 5 months, the liposomes were dialyzed against 7% trehalose solution and the content of taxol in dialyzed liposomes was measured by HPLC, and was found to be 93% of the initial concentration of taxol in those liposomes. This experiment demonstrates that taxol liposomes with trehalose as an excipient can be effective means of storing the liposomes frozen and be effectively used for clinical and therapeutic application after thawing the liposomes.
Male CD2 F1 mice weighing 22-25 gm were used in this study. Free taxol which is formulated in cremophor EL was diluted with saline to provide a concentration of 1.25 mg/mol. Taxol liposomes were prepared using cardiolipin, phosphatidyl choline, and cholesterol. The final taxol concentration in liposomes was 1.25 mg/ml. Ten mice in each group were injected with free taxol or liposomal encapsulated taxol at a dose of 25 mg/kg i.v. This is the highest dose of free taxol which can be injected into the mice because of the solubility limitations and alcohol content. The same doses were repeated on mice at day 5 and 9. No further injections could be given in mice which received free taxol because of the sclerosis of the vein. As shown in FIG. 2 by day 12, three mice in the free taxol group died because of toxicity whereas no toxicity or mortality was observed in mice which were injected with taxol encapsulated in liposomes.
The L1210 murine leukemia cancer was propagated in female DBA/2 mice. For therapeutic studies, CD2 F1 mice were implanted i.p. with 1�105 cells of L1210 leukemia and twenty four hours after tumor implantation, they were injected with free taxol or taxol encapsulated in liposomes. All the mice received dose of 6 mg/kg i.p. on days 1 to 5. Tumor bearing control mice were injected with normal saline in a same volume as experimental mice. All injections were made at 2% body weight basis. Mice were weighed on days of injection, doses of drugs were calculated on body weight basis and the survival time was recorded in days.
Table 1 shows the effectiveness of free taxol and taxol encapsulated in liposomes on the survival of mice bearing L1210 tumor. Mice when injected with free taxol at a dose of 6 mg/kg i.p. from day 1-5 exhibited a T/C of 135% (treated vs control). The same dose of taxol when injected as the liposome encapsulated drug produced a T/C of 178% demonstrating that survival of tumor bearing mice is substantially enhanced when treated with this modality of treatment. These studies demonstrate that not only the toxicities of taxol are reduced when encapsulated in liposomes but this encapsulation also provides a higher therapeutic ratio in tumor bearing mice.
HL-60 promyelocytic leukemia cells were grown in tissue culture in RPMl-1640 medium supplemented with 10% fetal bovine serum. All cultures were maintained in plastic tissue culture flasks and kept in an incubator at 37� C. in humidified air containing 5% CO2.
The growth inhibition method was used to determine the cytotoxicity of free taxol and liposomal encapsulated taxol. For these experiments, 1�105 cells in exponential growth phase were plated into 25 cm2 flasks. They were then exposed to varying concentration of free taxol and liposomal taxol for 72 hours at 37� C. Cells were counted in a hemocytometer and viability was determined by trypan blue exclusion. The cell survival was compared to the control cells and IC50 (inhibitory concentration for 50% of the cells) values for each drug was determined. As shown in FIG. 3, the IC50 values for free taxol were 0.0025 μg/ml and the same IC50 values for taxol encapsulated in liposomes were obtained. These experiments demonstrate that free taxol and liposomal taxol are as equivalent in their effectiveness to produce cytotoxicity to the HL-60 leukemia cells.
The cellular content of taxol was determined by high pressure liquid chromatography (HPLC). Briefly, exponentially growing cells were incubated in 100 mm petri dishes with drug containing medium at 37� C. The cells were treated for 1 to 4 hours with either free taxol or liposomal taxol at 10 μg/ml drug concentration, and were then centrifuged and rinsed twice with PBS. The cell pellets were suspended in 0.5 ml of 2% SDS solution and then sonicated for 5 minutes in a cup-horn sonicator. The cell homogenate was extracted with 2 ml of methanol. An aliquot of this solution was injected into HPLC for quantitative determination of taxol. As shown in FIG. 4, the cellular concentration of drug when exposed with free taxol was achieved to a maximum level at 1 hour, the value being 5.18 μg/107 cells. The same taxol concentration was observed at 2 and 4 hours of drug exposure. However, with liposomal taxol the cellular dry concentration was consistently lower than observed with free taxol. At 1 hour exposure, the cellular concentration of taxol was 2.3 μg/107 cells and this value was more or less similar to 2 and 4 hour exposure with liposomal taxol. This experiment demonstrates that even if the uptake of liposome encapsulated drug is less in HL-60 cells, the cytotoxicity is similar with either modality of treatment.
Resistance of tumor cells to chemotherapy is one of the major reasons for treatment failures in cancer patients. Over the last ten years, a major emphasis has been to define the mechanisms of tumor resistance to chemotherapy. This tumor resistance has been shown to be the result of amplified expression of multidrug resistance gene in cancer cells. The product of this multidrug resistance gene, p-glycoprotein of 170,000 daltons, functions as an efflux pump and confers resistance to cytotoxic action of structurally unrelated cancer chemotherapeutic drugs by producing lower intracellular levels of drugs.
Our studies demonstrate that liposome encapsulated taxol has significant capacity to overcome multidrug resistance. These studies were performed in HL 60/VCR cells which are promyelocytic human leukemia cells and are derived from parent HL-60 cells and are made resistant to vincristine demonstrating multidrug resistance phenotype. The HL-60 VCR cells were grown in media at 37� C. with 5% CO.
An accurately known number of cells were placed in tissue culture flasks and were treated with varying concentrations of free taxol, taxol encapsulated in liposomes and blank liposomes representing the same concentration of lipids as used for taxol. After 72 hours of incubation, cells in each flask were counted by hemocytometer and viability was determined by trypan blue exclusion. Percent survival of treated cells was determined relative to untreated control. Cytotoxic activity was expressed as IC50 which was defined as the concentration of drug resulting 50% survival of the cells compared to control.
The survival curves of HL-60/VCR cells after exposure to free taxol and liposome encapsulated taxol are presented in FIG. 5. The IC50 for free taxol in HL-60/VCR is 2.43 μg/ml demonstrating this cell line is 1280 fold resistant than the parent HL-60 cell line. However, the IC50 for liposomal taxol is only 0.37 μg/ml. This demonstrates that liposomal taxol sensitizes 7 fold the HL-60/VCR as compared to free taxol. Hence, it is apparent that liposome encapsulated taxol modulates drug resistance in the multidrug resistance phonotype which potentially would be a major advantage in a clinical situation where a large population of the patients fail to respond to chemotherapy because of multidrug resistance.
The cellular content of taxol was determined by High Pressure Liquid Chromatography. In brief, the multidrug resistance HL-60/VCR exponential growth phase cells were incubated in 100 mm petri dishes with drug containing medium at 37� C. containing either free taxol or taxol encapsulated in liposomes. The cells were treated for 1 to 4 hours with either of the drug and were then centrifuged and rinsed twice with PBS. The cells were suspended in cold PBS and counted, and centrifuged again. The cell pellets were suspended in 0.5 ml of 2% SDS solution and then sonicated for 5 minutes in a cup-horn sonicator (Heat Systems, Farmingdate, N.Y.). Resulting cell homogenate was extracted with 4 ml of methanol, vortexed for 1 minute and centrifuged for 20 minutes at 3000 rpm. The samples were read by using HPLC. The concentration of drug in 10 cells was calculated using a standard calibration curve for drug spiked cells and were then treated similarly.
FIG. 6 illustrates the accumulation of taxol in HL-60/VCR resistant phenotype cells following treatment with 10 μg/ml of free drug and liposomal encapsulated taxol for a period of 1 to 4 hours. The resistant HL-60/VCR cells demonstrated maximal uptake of liposomal encapsulated taxol and with time of exposure the intracellular drug accumulation correspondingly increased. By 4 hours, the drug accumulation was 10.54 μg/1077 cells with liposomal taxol whereas with free taxol it was only 3.04 μg/107 cells showing a threefold decrease in cellular uptake. The same relationship was observed at earlier time of cellular exposure and a difference of twofold drug concentration between free taxol and liposomal taxol was evident. These data suggest that modulation of drug resistance in HL-60/VCR cells can be partially explained by enhanced cellular drug uptake with liposomal encapsulated taxol. The enhanced cellular uptake and effective modulation of multidrug resistance in HL-60/VCR cells by liposomal encapsulated taxol demonstrates this modality of treatment can be of high clinical advantage for patients who have failed cancer chemotherapy previously. Overall, this modality of treatment is more effective than free taxol and can be successfully applied in cancer patients.
In accordance with the present invention, the present invention may be used to treat any mammal, such as a cow, horse, pig, dog or cat. However, it is particularly preferred if the mammal treated is human.
As referred to above, Table 1 is provided hereinbelow.
TABLE______________________________________Therapeutic Evaluation-of Free Taxol and Liposome EncapsulatedTaxol Against L1210 LeukemiaDose % T/C______________________________________6 mg/kg Free Taxol 1356 mg/kg Lipsomal-encapsulated 178 Taxol______________________________________
Generally, taxol, for example, may be obtained by isolation as a natural product from the bark of the Pacific Yew tree. See M. C. Wani et al, J. Amer. Chem. Soc., vol. 93, 2325 (1971). However, taxol or an antineoplastic derivative thereof may be synthesized in the laboratory. See J.-N. Denis et al, J. Amer. Chem. Soc., vol. 110, pp. 5917-5919 (1988).
Furthermore, taxol and the derivatives thereof in accordance with the present invention may be used to treat any form of mammalian cancer, particular those compounds which function by promoting the assembly of microtubules and which prohibit the tubulin disassembly process. However, the present compounds are particularly advantageous in treating mammalian lymphoma, ovarian, breast, lung and colon cancer, more particularly those of humans.
In accordance with the present invention, the liposomal-encapsulated taxol or antineoplastic derivatives thereof are generally administered intravenously or intraperitoneally to the mammal. Further, the present compound or compounds are generally administered in the amount of about 50-250 mg active compound/m2 of mammalian host surface area.
For a human, for example, of about 70 kg body weight, from about 0.5-5.0 mg active compound per kg of body weight is administered. Preferably, about 1.0-3.0 mg of active compound per kg of body weight is administered.
Thus, the present invention also provides methods of treating various mammalian cancers, particularly human cancers.
Moreover, the present invention also provides a method of modulating multidrug resistance in cancer cells which are subjected to chemotherapy. In accordance with this aspect of the present invention, it has been discovered that by using the liposomal compositions of the present invention, it is possible to reduce the tendency of cancer cells subjected to chemotherapy to develop resistance to the chemotherapeutic agents used for chemotherapy.
In particular, the present liposomal compositions not only reduce the tendency of cancer cells subjected to chemotherapy with taxol and derivatives thereof to develop resistance thereto, but the present compositions also reduce the tendency of cancer cells to develop resistance to other agents used for chemotherapy, such as anthracycline glycosides, for example.
Furthermore, in accordance with the present invention, it has been discovered that the present liposome compositions can be administered intravenously or intraperitoneally to an isolated portion of a mammalian body particularly a human body, such as an arm or leg, or in the case of a human, a hand. Then, that portion of the mammalian body may be subjected to a hyperthermia treatment. Hyperthermia treatments are well known to those in the art. Quite surprisingly, it has been discovered that upon effecting hyperthermia treatment the administered liposomes melt to provide a highly localized dosage of taxol or derivative thereof. Of course, the dosage administered will depend upon the body weight of the mammal being treated and the judgment of the treating physician. In accordance with this aspect of the present invention, the hyperthermia treatment may be administered before, contemporaneously or after administration of the active ingredient or ingredients, and the liposomes may either be administered locally or generally throughout the body.
Having described the present invention it will be apparent that one skilled in the art may make many changes and modifications to the above-described embodiments without departing from the spirit and scope of the present invention.
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Serving Size: 3 Capsule
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11th June 2009
British ambassador to Poland criticised for 'pushing' gay rights 37
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Adam Lambert now officially gay 31
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8th June 2009
Poll finds rising support for gay US troops 6
5:30 PM — A poll has found rising support for repealing the US ban on openly gay military personnel. The Gallup-conducted research found the biggest increases in support among conservatives and weekly churchgoers - up 12 and 11 percentage points respectively.
Supreme Court rejects challenge to military gay ban
4:47 PM — The Supreme Court has today rejected a challenge to the 'Don't Ask, Don't Tell' rule, which bans openly gay men and women from serving in the US military.
Gordon Ramsay calls journalist a 'lesbian pig' 21
12:35 PM — TV chef Gordon Ramsay has been condemned after calling a leading Australian journalist a "lesbian pig". He made the comment while giving a demonstration at a food show in Melbourne.
5th June 2009
Comment: Is Obama all talk and no action on gay issues? 36
6:43 PM — Impatience is growing amongst the USA's gay and lesbian community over President Barack Obama's slow approach to tackling the LGBT issues he promised to address.
LGBT group claims Iraq is waging a 'campaign of violence and murder' against gays 13
2:34 PM — An Iraqi gay group has said it has evidence the Iraqi government is involved with militia groups advocating violence and murder towards gays. Iraqi LGBT also described a statement from the Baghdad US Embassy as "offensive and insulting".
Study finds gay men do better at college but bisexual women lag behind 6
12:56 PM — New research has indicated that gay men achieve more at college than their straight male counterparts. However, the work also showed that bisexual women do worse during higher education than straight women.


text:
Orange for Animal Cruelty Awareness wants to
The Voiceless Dogs of Nassau, Bahamas
There are many homeless Beach dogs urgently needing a loving home.
There are many homeless Beach dogs urgently needing a loving home.
Animal abusers know they can get away with their crimes because courts rarely impose anything near maximum penalties.
The federal minimum wage would be $10.76 if it had kept up with inflation over the past 40 years. Instead, it's $7.25.
The NSA is looking through billions of our emails and phone records every day. Fight back to protect our privacy!
The USDA needs to act on violations documented by their own agency, and do their job to protect animals.
Animal welfare laws of Canadian provinces and territories must be changed to protect pets left in extreme temperatures.


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An electrical power generator includes a controller for making a full power capacity of the generator available for consumption by at least one intelligent load coupled to an output of the generator. The controller obtains data from which both a present output power of the generator and a power capacity of the generator can be determined. The controller then provides the intelligent load with data indicative of both the present output power and the power capacity of the generator for use by the load in controlling its power consumption.
1. An electrical system comprising:
a plurality of variable loads;
an electrical power generator that provides power to the variable loads via an output terminal;
a plurality of system sensors that sense a plurality of generator parameters related to the operation of the generator, the generator parameters including a voltage at the output terminal of the generator and a current drawn from the output terminal of the generator;
a generator controller that is coupled to the plurality of system sensors for receipt of data indicative of the plurality of generator parameters and that determines therefrom a present generator output power proxy and a generator power capacity; and
at least one load controller that is communicably coupled to the generator controller for receipt of data indicative of the present generator output power proxy and the generator power capacity and that controls a power consumption of at least one of the variable loads as a function the present generator output power proxy and the generator power capacity.
2. The electrical system of
3. The electrical system of
4. The electrical system of
5. The electrical system of
6. The electrical system of
7. The electrical system of
8. The electrical system of
9. The electrical system of
a prime mover that provides a rotational energy to the generator for conversion by the generator into electrical power; and
a prime mover controller that controls a rotation of the prime mover and that is communicably coupled to the generator controller via a communications network, wherein the generator controller is responsive to requests from the prime mover controller to adjust a power generation load of the generator on the prime mover.
This application is a divisional of application Ser. No. 11/156,216, filed Jun. 17, 2005 and entitled "Power Manager for an Electrical Power Generator" by Wei Wei Qi, Michael Rubbo and Richard Wainwright.
Reference is hereby made to U.S. Pat. No. 7,272,514 entitled "Protection System for an Electrical Power Generator" of Wei Wei Qi, Michael Rubbo, and Richard Wainwright. This application is hereby incorporated by reference as set forth fully herein.
The present invention relates generally to electrical power generation systems, and more particularly to an electrical power generator having self-monitoring capabilities that cooperate with at least one intelligent load to safely utilize traditionally untapped power generating capabilities of the generator.
Electrical generators are used in a wide variety of dedicated electrical system applications and locations that require power independent of a standard electrical grid. Commonly, electrical generators are the primary, if not only, source of electrical power on a vehicle or ship, or in a remote location such as on an oil platform, in a small town, on an island or along a pipeline. Electrical generators are also commonly used as a backup power source in locations operating primarily off the standard electrical grid.
Because of this primary role served by electrical generators, it is often desired to keep the generator fully functioning, or at least partially functioning, in all circumstances. Maintaining the generator at full capacity is complicated by the fact that the conventional generator is a slave to its loads, the maximum sum of which may greatly exceed a rated capacity of the generator. The generator itself cannot directly control its outputted power; it can only control its own output voltage. Rather, it is the generator's loads that control the draw of power from the generator. Thus, to avoid overloading conditions that may harm the generator, the conventional generator simply shuts itself off upon detection of overloading condition indicators, such as excessive temperature.
Generators typically have a rated continuous capacity that is determined as the maximum quantity of power the generator can produce for an indefinite amount of time without risking damage to the generator. Generators also have a rated surge capacity determined as a value the generator can sustain for a limited time, such as when the generator experiences a surge in power demands due to the transitioning of the generator's loads between on and off states.
The rated continuous and surge capacities are typically very conservative estimates of what the generator can actually handle. That is, most conventional generators can produce much more power than their ratings allow, and in use, much of the generator's power generating capacity is neglected. Nonetheless, to ensure their continuous operation, generators typically are selected to have a sufficient continuous capacity rating to handle all loads operating simultaneously at full capacity. This assumption often results in the selection of a larger capacity generator than what may otherwise be required or the addition of a second generator to allow a reduction in the load attached to the first generator. In many situations, however, these solutions are not appropriate due to cost, weight, size, and efficiency considerations. Thus, there exists a need for a generator capable of utilizing more of its capacity.
The present invention is a system and a method for making a full power capacity of an electrical power generator available for consumption by at least one intelligent load coupled to an output of the generator. In accord with the present invention, data is obtained from which both a present output power of the generator and a power capacity of the generator can be determined. Data indicative of both present output power and the power capacity of the generator are provided to the intelligent load for use by the load in determining its power consumption.
The present invention is a generator that incorporates a power management system that, in contrast to prior art generators that simply limit the generator to its rated capacity, seeks to capture and utilize the full power capacity of a generator.
As shown in
A rated continuous capacity and a rated surge capacity of a conventional generator are generally conservatively drawn from these power-time characteristics of the generator. That is, these rated values are typically determined from the generator's power-time relationship corresponding to a worse case scenario. The rated continuous capacity is generally determined as the steady-state value of the worse case scenario power-time relationship, while the rated surge capacity is determined as a multiple of the continuous capacity. The rated surge capacity may in fact be less than the actual maximum power the generator can produce.
The present invention enables the generator to produce power over its full range of capacities, rather than simply limiting the generator to its rated continuous capacity.
As shown in
The conventional power generating operations of generator 12 are well known. In operation, voltage regulator 20 receives a direct current (DC) voltage from battery 30. Alternatively, battery 30 could be replaced with a permanent magnet generator or another source of DC voltage. Voltage regulator 20 supplies a first DC voltage to exciter stator field windings 22, which in turn develop a magnetic field. Exciter rotor field windings 24 are rotated in this magnetic field to produce a first multiphase AC voltage. The first AC voltage is then supplied to rotating rectifier 25, which rectifies the first AC voltage into a second DC voltage for supply to main generator rotor field windings 26. The current in main generator rotor field windings then generates a magnetic field which in turn produces a induces a multiphase AC power at an output of main generator stator windings 28. This AC power is supplied to loads 14, 16, and 18 of generator 12, and also as feedback to voltage regulator 20.
Voltage regulator 20 uses this feedback to help maintain a constant voltage at the output of generator 12, which may otherwise vary due to factors such as a variable rotational speed of the rotor of generator 12. Voltage regulator 20 accomplishes this goal by measuring the output voltage of generator 12 and adjusting a current provided to exciter stator windings 22 as needed in a closed-loop fashion.
Generator 12 improves upon conventional generators by adding power management logic and communication abilities that allow for the capture and utilization of the full power generating capacity of generator 12. As will be more fully described below, the present invention essentially adds capabilities to generator 12 to monitor its own power production and various other system parameters and to determine therefrom its present power generating capacity. In other words, the present invention provides intelligence to generator 12 to enable it to determine answers to the questions: "What am I presently doing?" and "What am I capable of doing?" This information is then communicated to at least one intelligent load, which can adjust its consumption based upon the capabilities of generator 12. Thus, electrical system 10 is afforded the opportunity make use of traditionally untapped power capabilities of generator 12. In the embodiment of
As described above with reference to
Importantly, these system parameters also include the voltage supplied at the output terminal of generator 12 and the current drawn from the output terminal of generator 12. From these two values, voltage regulator 20 can compute a proxy for the present output power as the product of the voltage supplied at the output of generator 12 and the current drawn from the output of generator 12. While this value does not equal the actual power supplied by generator 12, it does serve as a fair representation of the power supplied. Thus system sensors 32 include hardware and/or software for determining the voltage provided at, and the current drawn from, the output terminal.
Another system parameter that voltage regulator 20 may include information about is the amount of time generator 12 has been operating at a particular output power. As described above, high power outputs can be sustained for a limited time period. Thus, generator 12 may include hardware and/or software for monitoring the length of time generator 12 has supplied a power outside the rated continuous capacity of generator 12.
Voltage regulator 20 evaluates the present output power proxy and the remaining system parameters to determine a present operating point of generator 12. In other words, voltage regulator 20 effectively determines which power-time curve is the appropriate curve, and where on that curve it is. From this information, voltage regulator 20 can determine the present power capacity of generator 12. This power capacity is the maximum power generator 12 can produce based upon the data indicative of output voltage, output current, and system parameters of generator 12. The power capacity of generator 12 may be greater than, less than, or the same as the present power being supplied; but importantly, it may exceed the rated capabilities of generator 12. For example, generator 12 will be able to produce more power on a cold day with prime mover 19 operating at high speeds than on a hot day with prime mover 19 operating at a low speed.
A further aspect of the present invention is use of intelligent loads (i.e., loads having their own controller for controlling their own power consumption) communicatively connected to voltage regular 20 over communications network 44. As shown in
Communications network 44 may be implemented with any communications protocol. For example, communications network 44 may be implemented with a controller area network (CAN), which is one of the ISO standard communications protocols.
Load controllers 34 and 38 receive and convert power delivered to loads 16 and 18 into useful forms for their associated loads. Load controllers 34 and 38 further receive and evaluate the present output power proxy and the power capacity of generator 12 to determine whether to adjust the power consumption of a respective one of loads 16 and 18. Load controllers 34 and 38 of loads 16 and 18 each have a performance set point to which they strive. Load controller 34 and 38 further include sensors (not shown in
For example, load 18 would constitute a large load if it were a vehicular air conditioning system in which load 40 is a compressor motor and load 42 is a compressor fan motor. In this example, the air conditioning controller (load controller 38) can evaluate both a quantity of power that generator 12 can supply and how the air conditioning system (load 18) is performing to determine whether to adjust its consumption. Thus, when the air conditioning system (load 18) is initially turned on to cool a hot space, and where generator 12 has excess capacity (that is, its power capacity exceeds its present power production), air conditioning controller (load controller 38) may prefer to operate the air conditioning system (load 18) at a higher consumption rate until its set point has been met or until generator 12 reduces its capacity. If generator 12 is operating above its capacity (the power capacity is less that its present power production), the air conditioning control (load controller 38) may choose to decrease its power consumption. Thus, rather than running continuously at lower settings, air conditioning system (load 18) may perform its job faster, taking advantage of the additional operating envelope of generator 12 for a period of time.
Load controllers 38 and 34 may also compute their own power consumption by including sensors to measure input voltages to loads 16 and 18 and currents drawn by loads 16 and 18. As with generator 12, load controllers 38 and 34 may compute and rely upon a proxy for the actual power consumed, such as voltage consumed multiplied by current drawn. By knowing their own consumption, load controllers 34 and 38 can evaluate their own operating point to determine their own capacity. Thus, much like generator 12 can operate over its rated continuous capacity, intelligent loads 16 and 18 may be able to operate over their rated continuous consumption levels. This is an improvement over prior art load controllers which evaluate only temperature or current, and shut off the device when either exceeds a predetermined limit. Another advantage to evaluating power consumption is that load controllers 34 and 38 can compare the actual power consumption to estimated power consumption for identification of component wear out, required maintenance, or imminent failure.
Loads 16 and 18 are prioritized within system 10 to prevent each of intelligent loads 16 and 18 from simultaneously grabbing excess power from generator 12 upon generator 12 announcing (broadcasting) its increased capacity. Thus, the load with the lower priority will not have an opportunity to increase its consumption until after the load with a higher priority makes its decision to adjust its consumption.
Load controllers 38 and 34 may also communicate their power consumption proxy with each other and with generator 12 over communication network 44 to allow for a more intelligent distribution of power. In this way, each of generator 12 and intelligent loads 16 and 18 can act in the best interest of electrical system 10, rather than operating in a vacuum where each is concerned only about its own performance. Such communication may also allow for dynamic assignment of load priorities. For instance, if load 16 is assigned a higher priority and is closer to achieving its set point than load 18, generator 12 may reassign priorities to result in an improved system performance.
By enabling load controllers 38 and 34 to communicate with voltage regulator 20, load controllers 38 and 34 can make requests of voltage regulator 20 to adjust the power provided to it. For example, if load controller 38 realizes that load 16 could use additional power to best meet its set point, but also aware that load 16 cannot tolerate any increase in current, load controller 38 may broadcast a request to voltage regulator 20 of generator 12 to "trim," or temporarily increase, its output voltage—the resultant effect being an increase in power without an increase in current.
Electrical system 10 can further be improved by adding "intelligence", or a controller, to prime mover 19 which causes rotation of the rotor of generator 12. This can be helpful in allowing prime mover 19 to control the electrical power generation load on it when needed. For instance, where prime mover 19 is an engine in a vehicle, and the vehicle is required to accelerate, as when the vehicle is attempting to pass in traffic or climb a hill, prime mover 19 can communicate a request to voltage regulator 20 of generator 12 to reduce power consumption. Voltage regulator 20 can respond to this request by reducing the output voltage of generator 12, thus reducing its generated power and its load on prime mover 19. Alternatively, prime mover 19 may request that the power generated by generator 12 be diverted from electrical system 10 to an alternative system of loads, such as a transmission system of the vehicle.
Voltage regulator 20 cannot control consumption by its loads. If intelligent loads 16 and 18 do not respond to requests by voltage regulator 20 to reduce their consumption, voltage regulator 20 can force a reduced power by lowering its output voltage. Because power is the product of the output voltage and the output current, this action results in a reduction in the power produced by generator 12.
In sum, the present invention is an electrical power generator that makes its full power capacity available for consumption by at least one intelligent load coupled to its output. The generator includes self-monitoring abilities that enable it to determine a present output power of the generator (i.e., what it is presently doing) and, from that, a power capacity of the generator (i.e., what it can do). These values are then broadcast to the intelligent loads via a communications network for use by the intelligent loads in controlling their own consumption.
Although the present invention has been described with reference to preferred embodiments, workers skilled in the art will recognize that changes may be made in form and detail without departing from the spirit and scope of the invention.
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text:
The project is to be constructed on PA land.
If selected for publication, it will appear as soon as possible on Haaretz.com.
Why is the Israeli establishment so bent on denying the existence of water discrimination? Because this time the Israeli establishment cannot wrap it in the usual security excuses it resorts to with other sorts of blatant discrimination.


text:
Tonight I'm Single
This great custom product in red from our department Accessories and Apron category can be printed just for you in the size and style you like. The design Tonight I'm Single was created by Prinz and uploaded to Spreadshirt for you to have printed on a Apron. Next to a host of other great customized designs, you can find this Tonight I'm Single design in Spreadshirt's Singles category. If you are interested in topics like Disco or Flirt, then you'll love Tonight I'm Single designs by Prinz. Spreadshirt also offers a huge selection of custom t-shirts, hoodies and accessories for the category Singles as well as top Love clothing. Prinz's designs have already impressed many of our customers, so we are sure that we've got right stuff for you! Spreadshirt is your destination for great designs of all kinds – whether it's Disco, Flirt or Love. We are sure that you will find something nice in our shop, there are many amazing custom Singles t-shirts, hoodies, or accessories for you to find! Tags: Design ID: 12656650
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Great Dads Get Promoted to Grandpa T-Shirts Designed by myfamily
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Class of 2015 T-Shirts Designed by Prinz
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For the chef in the family, this full-body apron is perfect for keeping your clothing clean. Complete with pockets for all of your kitchen utensils and condiments, this one is a must have for the kitchen, the grill or the open fire.
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text:
Le Desir Resortel, Phuket - Phangnga
- Free WiFi
Main amenities
- 12 guestrooms
- Breakfast available
- Bar/lounge
- Business center
- Airport shuttle
- Air conditioning
- Laundry service
- Tour/ticket assistance
What's around
- In Chalong
- Chalong Temple (2.1 mi / 3.4 km)
- HomePro Village (0.2 mi / 0.3 km)
- Chalong Pier (0.4 mi / 0.7 km)
Enter dates to check prices
Hotel Info: 866-539-8117from $19
- Deluxe Room
- Standard Room
Recommended hotels
At a glance
Key facts
Hotel size
- This hotel has 12 rooms
- Check-in time starts at 2 PM
- Check-out time is noon
Required at check in
- Credit card or cash deposit required
- Government-issued photo ID required
- Minimum check-in age is 18
Travelling with others
- No cribs (infant beds)
- No pets or service animals allowed
- Free WiFi in public areas
- Free WiFi in rooms
- Airport shuttle (available on request) *
Nearby Three Star Phuket - Phangnga hotels
In the hotel
- Cooked-to-order breakfast daily (surcharge)
- Bar/lounge
- Business center
- Tours/ticket assistance
- Dry cleaning/laundry service
In the room
- Air conditioning
- Minibar
- Balcony
- Shower only
- Hair dryer
- Satellite TV channels
- Free WiFi
- Phone
- Refrigerator
- Free bottled water
- In-room safe
Top Phuket - Phangnga hotels
Recently reviewed hotels in Phuket - Phangnga
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Nearby hotels
Le Desir Resortel, Phuket - Phangnga's small print
Also known as
- Le Desir Resortel
- Le Desir Resortel House
- Le Desir Resortel House Phuket
- Le Desir Resortel Phuket
This property does not have elevators.
For transfers, guests must contact the property before arrival at the number on the booking confirmation.
Optional extras
Rollaway beds are available for THB 500 per night
Airport shuttle service is offered for an extra charge of THB 900 per vehicle (one way)
We have included all charges provided to us by this hotel. However, charges can vary, for example, based on length of stay or the room you book.


text:
In Greek mythology, the Titans were powerful giants who once ruled the world. With these origins, it's easy to see why the word has come to signify size and strength. The Number Style of the Week exemplifies both. Titan is available in Pre-Cut Numbers in a variety of materials to help your customers make… read more
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July 3, 2015
Happy Canada Day!
Happy Canada Day to all of our Canadian customers, friends, and employees!
July 1, 2015
An Ode to Bleach
It makes things whiter than white And did you know it gives flowers a longer life? Killing germs, removing stains It relieves all sorts of household pains But here's a new use – giving uniforms a look that's unique, Bleach is the Number Style of the Week! Try it today in Pre-Spaced Numbers.
June 25, 2015