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Friday, February 26, 2010
© Copyright 2015 Albany Herald
Last Saturday evening we continued our trek with the Albany Symphony Orchestra to Baroque Germany lead, as usual by Claire Fox Hillard, this time as both conductor and violinist.
What is Baroque? -- in music, it is the period from about 1600 to 1750 following that of the Renaissance. Each of these "periods" has to do with changes in western European life styles as they are affected by politics, war, the economy, etc. Artists (painters sculptors, architects, musicians) being sensitively attuned to what is happening around them seek to express all this creatively. Johann Sebastian Bach life (1685-1750) spanned the height and beginning denouement of this period.
The symphony's sampling of the work of this broad genius is but a small one. Most of these musical periods were contemporary, in that people were only interested in the secular music popular in their time. Sacred music was a different story preserved by the Catholic Church. The music of three of J. S. Bach's sons -- Wilhelm Friedman, Johann Christoph and Carl Philip Emanuel Bach -- was far more popular than was his.
Apparently, Dad was a bit careless about preserving his own music, We know that there was much of it, that the requirements of his job was, to say the least, overwhelming -- producing "new" music each week, training the boys to sing it, teaching Latin in the church school, organ competitions.
Whew! Well, maybe he just didn't bother. Felix Mendelssohn uncovered this treasure trove when he discovered the great St. Matthews Passion (finished in 1729) and "introduced" (or re-introduced) it to an astonished audience 100 years later in 1829 at one of his Gewandhaus concerts in Leipzig, Germany where he was orchestra conductor. From that time until even now musicologists have made a kind of industry ("going crazy" to use a bit of levity) in trying to put together some semblance of a catalog of "all" that he wrote. And they're still discovering (and arguing about) stuff.
They've given it the name Bachwerkeverzeichnis. Wow! It simply means Catalog of Bach's Work. When you see BWV followed by a number, as in this program, that is an abbreviation of the impossible German word above. The number following is the order in which it appears in the catalog (they're still arguing about those). Dad, apparently, left few if any clues about any of this in his autographs (handwritten scores).
J.S. Bach's six Brandenburg Concertos fall with the genre of the concerto grosso which had been developing in Italy since the 1640's. They are characterized by small groups of solo instruments called concertini alternating with a larger group called tutti or ripieni. The whole mechanism is under girded by a keyboard instrument (or clavier, in Baroque parlance). This part is referred to as continuo which fills in the harmonic structure.
The orchestra gave us the full range of imaginative possibilities. Some highlights: the use of two continuo instrument (harpsichords) -- an orchestral one and a larger solo one raised from below to stage level; its broad lift displaying a colorful Baroque painting. In No. 5 in D Major, Marcia Mitchell Hood led the concertino with her characteristic masterful playing. Flautists Elizabeth Goode and Bond Anderson did yeomen's work throughout all six. No. 1 in F Major oboist Susan Brashier and bassoonist Shannon Lowe were standouts in the concertino (solo group). We are aware of slighting other fine musicians among the 27 artists who gave us such a splendid reading of this corner of this master's work.
There was so much music here and such bewildering contrast that we are strongly inclined to agree with the lexicographer Nicholas Slonimsky when he declared Johann Sebastian Bach to be "supreme arbiter and lawgiver of music."
James Marquis is a composer and emeritus professor of music at Albany State University, retired.
More like this story
- 'Musical Destination' makes a stop in Germany ( February 16, 2010 )
- Symphony taking classical turn to Vienna ( April 9, 2010 )
- Museum hosting Tallahassee Bach Parley ( February 25, 2014 )
- Symphony launches season of pride ( September 7, 2010 )
- Season ends on classical note ( April 27, 2010 )


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Sprinklebakes: Dessert Recipes to Inspire Your Inner Artistby Heather Baird
Synopses & Reviews
Publisher Comments:
How can you make cakes, cookies, and candy even MORE fun? Award-winning blogger Heather Baird, a vibrant new voice in the culinary world, has the answer: Cook like an artist! Combining her awesome skills as a baker, confectioner, and painter, she has created a gorgeous, innovative cookbook, designed to unleash the creative side of every baker.
Heather sees dessert making as one of the few truly creative outlets for the home cook. So, instead of arranging recipes by dessert type (cookies, tarts, cakes, etc.), she has organized them by line, color, and sculpture. As a result, SprinkleBakes is at once a breathtakingly comprehensive dessert cookbook and an artist's instructional that explains brush strokes, sculpture molds, color theory, and much more. With easy-to-follow instructions and beautiful step-by-step photographs, Heather shows how anyone can make her jaw-dropping creations, from Mehndi Hand Ginger Cookies to Snow Glass Apples to her seasonal masterpiece, a Duraflame®-inspired Yule Log..
"Line. Color. Sculpture. Mixed Media. These aren't your typical chapter titles for a baking book, but Baird, an artist and blogger, isn't your typical baker. With statements like 'Every dessert is just a draft,' and questions such as 'Who says a red velvet cake needs to be red?' she opts for blue velvet cupcakes. Creative freedom in the kitchen trumps tradition in this collection of more than 50 recipes that range from 'blank canvases' such as sugar cookies and gingerbread, to visually pleasing concoctions like Dale Chihuly — inspired Candy Nesting Bowls, Free-form Lollipops, and Origami Cookies. Practicality has its place in this unique title with a well-written primer on baking equipment, detailed technique instructions, and usable templates, but bakers and confectioners of all levels may be new to the author's 'sand' casting with brown sugar and making positive molds out of chocolate and balloons. In the over-the-top Book Cake with pages that could turn, based on a sculpture by Su Blackwell, one realizes vanilla cake has certainly come a long way." Publishers Weekly Copyright PWxyz, LLC. All rights reserved.
About the Author
Heather Baird is an accomplished painter and photographer whose works are in public and private collections across the United States, but her passion is creating eye-popping, mouthwatering desserts. She is a devoted practitioner of international confectionery technique who explores the outer limits of patisserie. She writes about her adventures in the world of creative dessert-making in her award-winning blog at sprinklebakes.com. Heather lives in Knoxville, TN, with her husband Mark and a mischievous pug named Biscuit.
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According to UNESCO estimates, there are approximately one billion people in the world who can neither read nor write. One sixth of the world population has never seen a schoolbook. In contrast, reading and writing in th
According to UNESCO estimates, there are approximately one billion people in the world who can neither read nor write. One sixth of the world population has never seen a schoolbook. In contrast, reading and writing in the industrialized nations are such commonplace objects of everyday life that they are completely taken for granted. We are taught to read and write at school, where we gain access to the cultural tool ofwriting, and it is this that forms the basis for all our further leaming activities. The teaching aids used in schools to impart us the skills of literacy are themselves based on the medium of writing. We can all remember what it was like to write things down on paper and in exercise books, to organize our notes in files, and to read up new information in text books. By teaching literacy to the individual, the schools as an institution are laying the foundation stone of literacy skills for entire societies. Many important developmental stages of this process in Europe took place in the Middle Ages, and the schools functioned as a dual participating force in this process. First of all, they were the institution in which competence in literacy was acquired, and they were themselves involved in leaming how best to communicate this task with the aid of the instruments of literacy. These tools, as employed in the schools, have undergone transformation over the centuries. Schoolbooks themselves have also had to adapt, to cope with the demands of literacy.…
|Michael Baldzuhn
|Document Type:
|Part of a Book
|Date of Publication (online):
|Year of first Publication:
|Publishing Institution:
|Univ.-Bibliothek Frankfurt am Main
|Release Date:
|http://www1.uni-hamburg.de/disticha-catonis/homepage/papers/schoolbooks-2006.pdf ; (in:) Franz J. Arlinghaus, Marcus Ostermann, Oliver Plessow, Gudrun Tscherpel: Transforming the medieval world. Uses of pragmatic literacy in the Middle Ages. A CD-ROM and
|HeBIS PPN:
|Dewey Decimal Classification:
|830 Literaturen germanischer Sprachen; Deutsche Literatur
|BDSL-Klassifikation: 06.00.00 Mittelalter > 06.04.00 Studien
|BDSL-Klassifikation: 02.00.00 Deutsche Sprachwissenschaft > 02.07.00 Textwissenschaft
|Licence (German):
|Veröffentlichungsvertrag für Publikationen


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ExOfficio Short-Sleeve Quick-Dry T-Shirt 53 56
EXCELLENT My husband loves these; they look great on. They wash and dry in less than a day and the fabric is light weight. May 8, 2015
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The 'ole Waffle Weave Material Texture - Duh! No where in your product description do you state that the material is a waffle-weave material. Even in the picture in your catalog and web site, it does not show the fabric texture. I have several Quick-Dry T-shirts, but I do not like the looks of the waffle weave texture, especially when worn under a dress shirt; hence, my reason for this purchase. Another T-shirt that you offer or sell - specifically states it is a weave texture material, that is why I chose to purchase this more expensive product. Sorry, you got me! I am sending them back for a credit card credit. Sorry.. February 18, 2015
I didn't believe it This is an expensive T shirt so I was both a reluctant and skeptical buyer. But I decided to give it a try. It not only has a good and comfortable fit but it is washable and dries quickly as advertised. In addition I sweat and a cotton T shirt lasts about a day. These seem to have an anti-odor factor of some kind. I can wear one 3 days before washing it.. I think you will like these. This is the first product I have written a review for. September 12, 2014
Simply the Best Took four of these T-shirts on a two-week trip through western Europe during the recent heat wave. Extraordinarily comfortable: light weight, silky luxurious feel on, wiicks away moisture so you stay cool in hot weather. EZ wash, dried in as little as 8 hours (sometimes less) if I rolled them up in a towel first and wrung hard to blot most of the water out, then hung on a hanger to dry. May seem pricey but worth it based on recent experience. An excellent product. August 13, 2010
Great for traveling with few items I bought a couple of these for my husband since we were going on a trip without laundry facilities. They dried quickly and held up well. He only had 2 and that worked fine for 3 week trip with sink washing. I would recommend. March 23, 2010
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sizes smaller than label the large was very tight under the arms and more like a medium December 27, 2014
Product:7092-ExOfficio Short-Sleeve Quick-Dry T-Shirt


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How To Solve Equations (Part 1)
How should you think about equations? And how can you solve them? Keep on reading to find out!
Page 1 of 3
In the last episode of Math Dude, we learned that an equation is a proclamation that the expression on one side of an equals sign has the exact same value as the expression on the other. But what exactly does that mean? And how do you use equations to solve problems and do useful things? Stay tuned because those are precisely the questions we'll be answering today and over the next few weeks.
Sponsor: This episode is brought to you by GoDaddy.com. GoDaddy.com offers everything you need to make a name for yourself on the Web, including domain name registration, website hosting, and more. Get 20% off your hosting plan purchase at GoDaddy.com by using the code hostpod60 at checkout.
How to Solve an Equation
When you plug in just the right number for the variable, the expressions on either side of the equals sign in the equation
must have the exact same value. After all, that's what an equation means! But how do you find that special value—the "solution" to the equation? As we'll see over the next few weeks, there are actually several different ways to do it. The method we're going to talk about today is by no means the best for most situations, but it's nonetheless a helpful one to keep in the back of your mind. This method is the most rudimentary of all methods—we're talking about good old brute force.
What does that mean in terms of math? It means that we start by guessing that the value of the variable must be equal to 1, and we then calculate the values that the left and right expressions will have. If the two expressions are equal, we're done. If not, we move on to the next guess and calculate the values of the two sides when the variable is equal to 2. We then check again and we repeat as necessary until we find the value of the variable that gives us a match.
Here are the values of the expressions on the left and right side of our equation for guesses ranging from 1 to 5:
For guesses of 1, 2, and 3, the value of the left expression is greater than the value of the right. For a guess of 5, the value of the left expression is less than the value of the right. And, lo and behold, the left and right expressions have the exact same value for a guess of 4. Which means that this equation is solved by setting the variable to 4.


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O-H-I-O Share your pride
"Families" Images (1990)
"Buckeye Pride in the Outer Banks of NC!"
by Carrie Dotson
We came across so many Buckeye fans while vacationing in NC this summer. Our family chose to show our pride at sunset at Jockeys Ridge State Park in the Outer Banks of NC!Beach, Families, US
"O-H-I-O Disney Style"
by Cindy Search - Future Buckeyes
Search family vacation 2013Families, US
"Scarecrow O~H~I~O"
by Mitzi Pfeiffer Kitchen - BS Human Ecology/FCS '84
Ohio State grad, Mitzi Pfeiffer Kitchen '84 celebrating Autumn 2013. Posing with her husband Chris, son Clint and their scarecrow outside their home in rural Forest, Ohio before heading down to the OSU-Wisconsin game!Alumni, Families, Game day
"Buckeye Love In London"
by Laurie Schultz-Hixson
Hixson-Lipinsky Family showing our home town pride under the London Olympic Rings! Go Bucks!!!Europe, Families
by Angela Zabala
The Zabala family from one of the beautiful beaches in Puerto RicoFamilies, Latin America/Caribbean, Silhouettes
"Jesse Owens tribute at US Olympic Hall of Fame"
by Skylar McCullough - International Studies 2013
Taken at the US Olympic Hall of Fame in Colorado Springs, CO. My parents, grandma and I figured in front of Jesse Owens' picture in the Hall of Fame would be a great spot for an O-H-I-O.Alumni, Families, US
"Family O-H-I-O on the beach in Maine"
by Daryl Scott - 2006 Graduate
Scott family photo on Willard's Beach in Portland, ME. Kids ages 5 and 3 made the I-O like champs!Beach, Families, Shadows
"Disney O-H-I-O"
Family Trip to Disney.Families, Travel/Vacation, US
"OSU Alumni Johnson Family 2013"
by Barbara Rich Johnson - MPA '80
Hampstead-Heath Park overlooking London was the site of this OSU celebration by: Bob and Barb Johnson (both MPA), son David Johnson (MArch '13) and Daughter-in-law Alison Johnson (DDS '13.)Alumni, Europe, Families
"O-H-I-O in Malibu"
by Melissa Oliver - Circulation Technology, 2006
The Oliver family out for a pre-game surf before watching OSU vs. CALAlumni, Families
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The Robert C. Parker School in North Greenbush last week hosted students from St. Peter's School in Barcelona, Spain. The Spanish students stayed with Parker families during the cultural exchange. The visiting students were surprised by the snowstorm in Albany and enjoy sledding at the school.
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On Obama's Unwinnable Battle Against Religious LibertyBy
What a crazy week it has been, between the Obamacare/HHS mandate, over 150 bishops speaking out against it, and the battle between Susan G. Komen and Planned Parenthood.
A great many people are visiting this site today because of my comments on the Komen situation — my most recent thoughts on that can be found here (ongoing updates can be found at my twitter page @AmericanPapist — the story is very fast moving and complex).
But I don't want to lose track of the "bigger" story – Obama's war against religious liberty in this country and the Catholic effort to win this war definitively.
Peggy Noonan calls this a "battle the President can't win" in her syndicated column today for the Wall Street Journal and says "President Obama just may have lost the election" because, in going after the religious liberty of Catholics, he has "awakened a sleeping giant":
If [Catholics] stay strong and fight, they will win. This is in fact a potentially unifying moment for American Catholics, long split left, right and center. Catholic conservatives will immediately and fully oppose the administration's decision. But Catholic liberals, who feel embarrassed and undercut, have also come out in opposition.
The church is split on many things. But do Catholics in the pews want the government telling their church to contravene its beliefs? A president affronting the leadership of the church, and blithely threatening its great institutions? No, they don't want that. They will unite against that.
I hope and pray she is exactly right.
Stephen White (a valued CV contributor) writes in National Review about the brazen politics behind Obama's decision — exploding the myth that this was about helping women. It wasn't. It was about asserting the raw power of the state over people and institutions of faith:
Perhaps the most telling moment in the [White House briefing] call came when one official conceded that the administration has no idea how many people this exemption is expected to "help." In other words, in all HHS's "careful considerations," there was no comparison of the "benefit" (however marginal) of this exemption versus possible alternatives.
It mattered not at all whether this narrow exemption, when compared to a more robust exemption, expanded coverage to one more woman or one million more women. Coverage simply had to be expanded as a matter of principle. Whoever meets the requirements of the narrow exemption, and decides to take advantage of it, should be grateful they are allowed even that.
… Overall, the administration's defense of the HHS mandate has been an exercise in condescension. In their eyes, the "religious exemption" wasn't carved out so the government could protect constitutional rights while it addressed what it saw as a compelling interest — those rights, we are told, are not even at issue. In the eyes of this administration, the "exemption" is a benevolent, even gratuitous, concession. HHS even allows a whole year for certain cultural laggards (read: Catholics) to bring their "religious beliefs" up to speed. Is that not generous?
No kidding.
Luckily, a rising chorus of voices (in addition to all those I have already cited over this past week) are speaking out. Radio pundit Hugh Hewitt writes a "memo" to the U.S. Bishops:
It may have taken a few days to sink in, but by now you should all have realized that President Obama has opened a massive assault on the Roman Catholic Church in America the likes of which none of you have ever experienced and for which few of you have prepared.
He goes on to interview Presidential candidate Rick Santorum, who says he has condemned the Obama/HHS decision "in every speech I've given today." And that Catholics should respond to the law with "civil disobedience."
GOP Presidential candidate Mitt Romney has published an op-ed in the Washington Times on the subject of standing up for Catholics and religious liberty:
I stand with the Catholic Bishops and all religious organizations in their strenuous objection to this liberty- and conscience-stifling regulation. I am committed to overturning Obamacare root and branch. If I am elected President, on day one of my administration I will issue an executive order directing my Secretary of Health and Human Services to issue a waiver from its requirements to all 50 states. And on day one I will eliminate the Obama administration rule that compels religious institutions to violate the tenets of their own faith.
Imagine that: we have the possibility of electing in November a President who will respect the constitutional right of American citizens to be, to live, Catholic.
That's a battle worth winning. Let's not forget it.
16 thoughts on "On Obama's Unwinnable Battle Against Religious Liberty"
We have every reason not to believe Mitt Romney.
Regarding the comment "do Catholics in the pews want the government telling their church to contravene its beliefs? A president affronting the leadership of the church, and blithely threatening its great institutions? No, they don't want that. They will unite against that." Let's pray we will unite. But recall just one historical precedent.
Could any English Catholic in, say, 1530, have imagined that in just eight years, (1538), that the twelve hundred year universal devotion to Catholicism of the English common people, not to mention the monasteries and Church lands so frequently devoted to the care of those same commoners, could be legislated from the scene, with the condemntation to barbarous execution of faithful adherents who refused to relinquish their devotion? (Keep in mind that the 1538 execution of St. Thomas More and Bishop St. John Fisher, by beheading, resulted an act of "compassion" by Henry VIIIth–a royal commutation pronounced for St. Thomas only on the very day of execution to forego the normal punishment for treason: hanging, drawing, and quartering. The innumerable ordinary priests, lay persons, and nuns who persisted in the faith received not such commutation. These sentences were imposed and carried out by fellow Englishmen, former members of the Faith. Does anyone sincerely think Nancy Pelosi will act differently from Thomas Cromwell or Bishop Cranmer when his own Bishop is tried for refusing to acknowledge this regulation? The traitorous apostates of the English reformation were motivated specifically by the desire to seize the great Catholic institutions for their own profit. Human nature has not changed between 1538 and 2012.


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Hotels in 72457 - Portia AR
Only hotels in 72457 zip code are listed below. Search for cheap and discount hotel rates in Portia, AR for your upcoming leisure or conference / group travel. We list the best 72457 hotels and motels so you can review the Portia hotel list below to find the perfect lodging. Hotels in Lawrence county and area code 870 are also listed.
72457 Hotels/Accommodations
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Born: February 04,1972 Secunderabad, Andhra Pradesh, India.
Zodiac: Aquarius
Biography: Sekhar kammula is an indian film director, screenwriter and producer, known for his works in telugu cinema. his first film, dollar dreams was a critical success, and won him the national film award for best debutant director. he has won six andhra pradesh state nandi awards. in 2011, sekhar was among the director's delegation to represent indian cinema at the cannes film festival.See full bio Read on Wikipedia
Sekhar Kammula : Filmography
- Avakai Biryani
- Happy Days (2007 Film)


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Annie CissySKU: #7907886
Product Information
- Your feet can walk the walk, but let your style talk the talk in the Cissy from Annie®.
- Synthetic leather upper with large floral adornment.
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Benefitfocus will hire 300 people in the next two years, the Daniel Island software company announced Tuesday as part of a ceremony officially unveiling its newly outfitted Design + Engineering building.
Most of that growth will be on Daniel Island, where the company's headquarters and the expansion offices were built as neighbors in 2006, said co-founder and CEO Shawn Jenkins.
The new building, most of whose 80,000 square feet were unfinished until this year, eventually will be able to house 475 employees — considerably more than the 325 who now work in the headquarters of the self-described "largest benefits technology provider in the U.S."
Jenkins called the new office space "a social workspace for the best minds in all the country to be attracted to as we grow" and a "most awesome place to hang out."
Charleston Mayor Joe Riley called Benefitfocus a "great, classic American success story" and the new offices and hiring plans a "wonderful signal of continued growth."
When dozens of Benefitfocus employees assembled outside the building responded by jangling their company's traditional cowbells, Gov. Nikki Haley, the next speaker at the afternoon ribbon-cutting, was ready with a riff.
"There's one thing I noticed: We need more cowbells," she said in a reference to a famous "Saturday Night Live" skit. "We are about to have about 300 more cowbells."
Benefitfocus, which was founded in 2000, now has 18 million users on its benefits-management platform in all 50 states and 66 countries, Jenkins said. In addition to the Daniel Island complex, the company has offices in Greenville, Oklahoma and San Francisco and more than 700 employees in total.
While the new offices were designed with user-interface and data-manipulation specialists in mind, the projected hiring spree also will include workers who help customers use the firm's software.
"You don't have to be a software engineer," Jenkins said.
The new space has a spare-no-expense feel about it. The third floor features hardwood floors and exposed brick, coffee machines and couches, antique light bulbs, Fender guitars and even a red Ducati motorcycle to set the mood for creative collaboration. A big video room is in the works.
The second floor also is now occupied, and there is room for expansion in almost 20,000 square feet on the first floor.
David Thorn, an analyst who was hired at the company about a year ago, moved into the new building a few months ago.
At headquarters, there was "definitely a lot of competition for focus to get stuff done," he said.
"Over in this building it's definitely much easier," the 39-year-old Daniel Island resident said, noting his entire information security team is grouped together. "I definitely feel more relaxed here."
Haley said she was impressed, calling the open work atmosphere contagious.
"I'm jealous," Haley said to Jenkins and his family on her way out of the new office. "I want to be them when I grow up."
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New Okuma Plant Relies on Automation, Production Control
The company says the DS1 facility in Japan is capable of 2 times the production capacity and 1/2 the lead time of the previous site.
A Smooth Transition to Five-Axis Machining
A mold manufacturer that specializes in precision, thin-walled container molds chose an integrated approach to establishing an effective five-axis "3 + 2" machining process.
The Value of a Portable Second-Op Machine
A portable second-op machine can make more effective use of labor while freeing primary machines to carry out the complicated work they were designed to perform.
Digital Dental Prosthesis Production
Digital dental technologies are helping to transform every aspect of the dental industry. The days of tedious, manual production of crowns, copings and bridges are fast disappearing.
Smart Machining Centers
These days, precision machine shops are often looking to expand the range of work they can take on profitably. It is not enough, in many instances, to be exclusively a turning shop.
"Right-Sized" Machine for Structural Aerospace Parts
This five-axis machine offers a compact footprint and atypical automated pallet changing system for small, yet challenging aerospace structural components.
What it Takes to Tackle Tungsten
When this aerospace job shop settled on machining tungsten alloys and other heavy metals as its specialty, it had to have a machine tool, cutting tools, workholding and process know-how to succeed.
Automation at Aztalan Engineering
A contract manufacturer expands its capacity using various approaches to feeding the machines.
Composites Technology at F-35 Suppliers Conference
A recent conference highlighted composites milling equipment as well as a new seven-axis fiber-placement machine specifically designed for the tricky material used to create critical F-35 components.
Taking the Long View on Short Runs
Certain jobs require a processing strategy that strikes a balance between the needs of high-volume production and low-quantity toolroom work. Reorganizing material flows and investing in machining centers designed specifically for small lots helped...


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The sides played out a 0-0 draw at The Den that saw Scott Dann have his head bandaged after being caught by Rob Hulse's elbow.
The same player also suffered a blow to the head after colliding with Lions defender Danny Shittu in the second half.
Referee Martin Atkinson issued seven yellow cards during the game, while Bradley Orr was left "struggling to breathe", according to Rovers manager Appleton, after one of his ribs was cracked in a challenge with Shittu.
Appleton was unhappy with how his players were treated but Jackett denied his players had purposely targeted the opposing side.
"There were a lot of tackles flying around today and a couple of cheap shots going on out there, which is disappointing," said Appleton.
But Jackett insisted his players had not acted improperly.
"Cheap shots? I don't think that was the case," he said. "I don't think that was my players at all."
Millwall midfielder Jack Smith was also surprised by Appleton's comments.
"I didn't see any cheap shots. They seemed to fall over if we breathed on them," he said.
The two sides meet again for the replay at Ewood Park on Wednesday night.


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Written by Valerie Skillern • Issue: November 7, 2013 • Campus: Anschutz Medical Campus, CU Denver, CU system, CU-Boulder, UCCS • Tags: employee services •
Ask Erik Jensen about the future of Social Security, and he'll refer you to a powerful group of people, 75 million strong, who are ensuring the program's viability.
The baby boomer generation — born 1946 -1964 — is increasingly moving toward retirement. Its members have the backing of AARP, one of the country's largest lobbying groups. And they're relying on Social Security to see them through their golden years.
"I think this is a piece of everyone's future," says Jensen, district manager of Colorado and Wyoming for VALIC Financial Advisors Inc. "There are some folks at CU that might not have Social Security, but their spouse might. Or (they have Social Security from working) years of summer jobs."
When Jensen gives his presentation, "Social Security and Your Retirement," as part of the university's "Preparing to Retire" seminars, he hopes to see several Gen Xers, Yers and Millennials among the crowd. Even if the program does someday fade into oblivion, Jensen says it's crucial for even today's youngest workers to think about how Social Security might play into their financial portfolios.
"Social Security and Your Retirement" is steeped in the notion that you must understand your finances today to decide where you want them to be tomorrow. Jensen's talk also uncovers several Social Security strategies, potential setbacks and interesting facts.
Some examples:
Potential setback
Interesting fact
Learn about Social Security and much more at "Preparing to Retire," seminars, sessions and fairs organized by Employee Services and set for Nov. 18, 19, 21 and 22 on each CU campus.
See the event calendar to find Jensen's seminar and more.
Post your comment here.
(Log in required. Need to register? Click here.)


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Japanese musician who rocks the hardest
Yoshimi P-we who plays with the psyche-noise-experimental group the "Boredoms" and is the leader of her own band "OOIOO." She is a musician of extraordinary talent and uniqueness, and is the kind of musician that makes you want to quit whatever your doing and take up drums for the rest of your life, with only hopes that you'll be an ounce as good. Yoshimi has been a prolific collaborator since the mid 1980's, when she began working with Yamantaka EYE on his UFO or Die project (a cut-up, noisy affair directly related to EYE's previous work with Hanatarash and emerging Boredoms recordings).
She joined the Boredoms lineup as lead drummer, and would become the most consistent member (along with EYE) for the next 20 years. Associations with Sonic Youth led to Yoshimi's involvement in Free Kitten, with Kim Gordon (Sonic Youth) and Julie Cafritz (Pussy Galore), and she has continued to lend her significant skills as a multi-instrumentalist and producer for a variety of bands throughout the 90's and 00's.
What sets Yoshimi apart from other eternal collaborators is that she seems to always be a driving force behind bold experimentation in sound and composition. This is most clearly apparent in the progression of Boredoms from punkish noise and no-wave through layered electronics and, most recently, rapturous tribal and elemental creations. The evolution of Yoshimi's own side project, OOIOO, has mirrored this shift to rhythm-based communications with nature. With Yoshimi acting as producer, singer, trumpeter, drummer, and guitarist, OOIOO's albums are the manifestos of sun and mountain, fusing chants, repetitive rhythms, electronics, and sinewy guitar riffs to create meditations and explosions alike.
Check out, in particular, Gold and Green (2005), and Taiga (2007) for a thorough representation of the sublime presence of OOIOO, and to experience the culmination of Yoshimi's significant mark on experimental, elemental sound.
If you don't have a subscription to award-winning 80-page quarterly Bitch magazine, it's definitely time to start one.
Comments1 comment has been made. Post a comment.
I love OOIOO. Good call! She's an amazing musician.
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In the past, I have written about the values of participation and localization in development. These two elements have, over the years, taken a prominent place in debates and discourses on what could possibly be an effective route towards economic stability and equality.
However, a new report from World Bank economists Ghazala Mansuri and Vijayendra Rao says otherwise. In Localizing Development: Does Participation Work?, Mansuri and Rao closely examines whether local aid and participation and the practice of decentralization really works for development. Decentralization is defined in the report as 'efforts to strengthen village and municipal governments on both the demand and supply sides'.
One of the key points underscored in the report is that like general and centralized development, localized development is not impervious to the threat of corruption, abuse, and misuse of resources. Throughout the years, the World Bank has been consistent in initiating research projects that aim to determine the most pressing development issues that need to be addressed, and one challenge that has been persistently showing up in these reports (and one which I have previously written much about) is corruption. Now that the new World Bank report has revealed that some forms of corruption may be present and even encouraged by giving local authorities and units control over development projects, it seems as if corruption and abuse has inundated every crevice of developing societies, even those that once seemed as the 'apt' channels for development.
The problem that this new Localizing Development presents is troubling: local participation and control, something that was once considered as one possible way to combat corruption, now appears susceptible to the very same evils we thought it was against. Note that the report was birthed to address the question as to whether several innovative trends of "doing development differently" really work. One of these emerging innovative ideas is Jamie Drummond's concept of 'crowd-sourcing' the new Millennium Development Goals by using mobile and internet technology to conduct "the first ever truly global poll and consultation on "What the World Wants"". The thing is that this idea is neither the only nor the first of its kind. In fact, it is highly representative of how the world today values public participation as one of the most essential, if not the ultimate, tools for development.
However, according to the World Bank report, one common mistake or illusion among development organizations and institutions is that it is relatively easy to mobilize and foster civic engagement among poor communities because of their 'ample social capital'. It elaborates that more than the amount of social capital in a given community, what is imperative to fully achieve community participation is a deeper understanding of how to get the people to "act in a way that solves market and government failures". In light of this, the researchers add that "genuine efforts at inducing civic engagement require a sustained long-term commitment and a clear understanding of the social and political forces at all levels of society."
Humphrey Kariuki Ndegwa is an African visionary and global industrialist, heading an enterprise that spans most of the African region. In his blog HumphreyNdegwa.com, Humphrey writes about his passions and interests, namely: African economy, sustainable development, and responsible entrepreneurship.


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The current population of Oregon is 3,922,479 with the median age of 38. Oregon's median household income is $49,316, and the average household net worth is $465,183. 26% of Oregon's population are long term residents having lived in their homes for more than 5 years, while 17% of Oregon's population have moved in the last year.
|United States
|Median Household Income
|Average Household Net Worth
|Long-term Residents (5+ years)
|Annual Turnover
|Median Age
|38 years
|37 years
Age distribution represents the distribution of the population in Oregon by age group. In Oregon, the male-to-female ratio is 1,940,936:1,981,543, which is 1% higher than the ratio of United States, which is 155,506,097:160,846,200. Age demographic data is sourced from census, 2015.
Crime rate index represents the average crime rate for a local area in comparison to nearby areas and the national average. A crime index of 100 represents the national average. Oregon, has 23% more property crime than the national average, and has 39% less personal crime than the national average
Marital status represents the percent of residents in Oregon that are single, married, widowed and divorced. In Oregon, 76% of people are married and 24% of people are single. The percent of people married is 3% higher than the ratio of United States, which is 73%. Marital data is sourced from census, 2015.
Household income distribution represents the distribution of Oregon income brackets at the household level. Overall, the median household income for Oregon is $49,316, which is 7% lower than that of United States ($52,961). Income data for Oregon is sourced from census, 2015.
Education data represents the highest level of education attained by residents in Oregon. In Oregon, 11% of residents 18 and over graduated from high school and 29% completed a Bachelor's degree or higher, which is 1% higher than that of United States. Education statistics is sourced from census, 2015.


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The Thule Xsporter XK3 Adapter for Toyota Tundra and Tacoma allows the Thule 500 Xsporter Pro pickup truck rack systems to attach to pickup trucks equipped with a bed track system....Continue Reading
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The Saris Locking Hitch Tite secures your Saris bike rack to your vehicle with a theft-preventing lock. The Saris Locking Hitch Tite is compatible with the Saris Bike Porter Hitch,...Continue Reading
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The Yakima Side Loader Bracket installs in the space between the top of your camper shell and the side window. You are then able to attach Yakima RainGutter Towers to the Yakima Side...Continue Reading
The Saris B.A.T. Spare Tire Plate is the vehicle-specific mounting plate for the Saris B.A.T. Spare Tire Carrier. The Spare Tire Plate adds security and decreases wobble.
The Thule One Key Lock Cylinder system comes with 2 keyed alike locks and two keys. This Open Box item may come out of its original packaging but is otherwise in great condition.
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Firstly what is CPOL, well if you have had a look around this site you have probably got an idea. However officially it stands for the civilian personnel online website (cpol.army.mil). Although this is an arm of the military you are not considered a soldier at all. If you get a Cpol job, you are generally part of a civilian corps. This can be an army, Navy or Air Force civilian corps. However getting one of these jobs is pretty much like getting any job. You have to apply, get a resume together, go to an interview and then wait and hope you got the job.
What is the CPOL Resume Builder?
To help speed up the recruitment process, the army has a special system for submitting resume's known as the CPOL resume builder. It is based on the army's Centralized Resumix System. This system allows for the online submission of an applicant's resume. It allows for a standardized format for the resume and empowers the reviewer at the other end to make a faster decision regarding the position available within the army. The system allows for supporting information, like qualifications, employment history and more, to be submitted. A comprehensive profile of the applicant can built through online contact only.
What are the benefits of using this system?
One of the main benefits is that you are doing this all from the comfort of your desk at home. You do not have to visit and army recruitment office and this allows for a cool down period. Some people see the army as a bit of a last resort. Whilst this is most definitely not true, the army isn't for everyone. So a cool down period is a bonus and will give those who truly do not want a military job a chance to look for something else.
The army is pushing for all recruits to use this system as it allows for easier tracking and faster turnaround on job applications. The army wants to fill these jobs as quickly a possible and if you are determined to get an army job, this will expedite your move into a civilian personnel position within the army.
Finally, the flip side to the resume builder is the Answer tool. Answer is a acronym for (The Applicant Notification System Web-Enabled Response tool). It allows job applicants to track their application history, check the status of their resume and view all the information (including the resume) they have submitted to CPOL.
Final Thoughts on the CPOL resume Builder
The resumix system will take your skills and try and match them to the right job. So make sure that your resume includes the most up to date and accurate information about your working history possible. It only allows one resume per person as they are trying to fit you to the most appropriate job they have going at the time. However you are able to make changes but this will eat up valuable time and may cause the system to match you to the wrong type of job. So try and get as right as possible the first time.


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Making a Combat Rogue is possible, but difficult in any environment. With that stat generation, its pretty easy. If you have that stat generation and are looking for "low optimization" then its painfully easy.
The trick? Just do it. Focus on getting a lot of to-hit through your feats and your magic items. Challenge yourself to use smart play over a smart build, particularly if you are a low level.
That stat array is really your saving grace, though. With it you can easily have a high Dex, go finesse rogue, and still have decent damage. By the benchmark fr your DPR, with Sneak Attack, is roughly 1/3 of standard target's HP at your level.
What level are you starting at?
Some notes:
- The Thug Archetype, particularly when combined with Enforcer, is disgusting.
- Scout is good for reliable damage.
- Filcher is interesting and fluffy, but may or may not be useful.
- Talk to your GM about the types of enemies you'll be facing--monsters vs people-sized. If the former, then Risky Striker and Big Game Hunter are, bar none, you best feats.
- Ninja Trick -> Pressure Points is fun.
- For a Two-Weapon Fighter, start with a cracked pale green ioun stone.


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Quantity Available:
Troy Lighting, headquartered in California, designs and manufactures indoor and outdoor lighting fixtures, utilizing hand-forged iron and hand-applied finishes to create quality products with high-style appeal.
The La Grange Outdoor Postmount is available with the following:
- Clear Seeded glass shade
- Hand-forged iron construction
- Old Bronze finish
- Includes a 3" post fitter
- UL Listed for wet locations
- Post not included
- One 100 Watt 120 Volt Medium Base Incandescent lamp (not included).
- Fixture: Height 27", Diameter 16"
Manufacturer IDs: view
Need help with some of our terminology? Check out Lumens' Lighting & Design Glossary.
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An apparatus and method for providing a real-time video display and a temperature map display of an object, in particular a flame, comprises a single CCD video camera and optical equipment which focuses separate light bundles onto a photosensitive surface of the camera. A separate band pass filter is used in each light bundle to filter selected different wavelengths of light. The video signal from the camera is used in a video digitizer to obtain data which can be used to calculate a temperature map based on the different wavelengths of light of the two bundles. The video signal is also used to produce a real-time video display of the object.
1. An apparatus for providing a real-time display and temperature map of an object, comprising:
a single CCD video camera having a photosensitive surface;
dividing means for dividing a bundle of light from the object into two light bundles;
filter means for only passing a different selected wavelength of light from each divided light bundle with all other wavelengths being absorbed or reflected;
optical means for focussing the two selected wavelengths of light passed from the divided light bundles onto the photosensitive surface of the single CCD video camera, the video camera producing a video signal therefrom;
pathlength compensation means in one of the divided light bundles for adjusting an optical pathlength of the one divided light bundle to be substantially equal to an optical pathlength of the other divided light bundle;
a video digitizer connected to said camera for digitizing the video signal into a digitized signal;
a first video display connected to the video digitizer for producing a real-time display of the two selected wavelengths of light passed from the divided light bundles;
processing means connected to said digitizer for processing the digitized signal to form temperature map data calculated from relative intensities of the two selected wavelengths of light passed from the divided light bundles; and
a second video display connected to said processing means for providing a temperature map display corresponding to the temperature map data.
2. An apparatus according to claim 1, wherein said filter means includes a separate bandpass filter in the path of each of said divided light bundles.
3. An apparatus according to claim 1, including a neutral density filter in the path of one of the divided light bundles having highest intensity for equalizing the intensity of both divided light bundles before they reach the video camera.
4. An apparatus according to claim 1, wherein the optical means focuses the two divided light bundles onto separate locations on the photosensitive surface.
5. A method of forming a real-time display and temperature map of an object, comprising:
splitting a light bundle from the object into two divided light bundles;
passing a different selected wavelength of light from each divided light bundle with all other wavelengths being absorbed or reflected;
focussing the two selected and different wavelengths of light passed from the divided light bundles onto a photosensitive surface of a single CCD video camera to produce a video signal;
adjusting an optical pathlength of the one divided light bundle to be substantially equal to an optical pathlength of the other divided light bundle with pathlength compensation means;
digitizing the video signal;
using the video signal to form a first video display of a real-time display of the two selected and different wavelengths of light passed from the divided light bundles;
calculating from the digitized video signal a temperature map of the object; and
displaying the temperature map on a second video display corresponding to the temperature map data.
6. A method according to claim 5, including dividing the bundle of light coming from the object using a beam splitter to form two divided light bundles and using a mirror to divert one of the divided light bundles so that it extends in a path which is substantially parallel to the path of the other divided light bundle.
7. A method according to claim 6, including focussing the parallel divided light bundles onto separate locations of the photosensitive surface.
The present invention relates in general to flame-monitoring equipment, and in particular to a new and useful video camera based measuring instrument which provides real-time displays of an object along with a two dimensional temperature map of the object which is determined using two-color pyrometry.
Optical pyrometry is a measurement technique in which the temperature of an object is determined based on the magnitude of the thermal radiation emitted by the object. In general, the radiant energy emitted by an object is measured at one or two wavelengths. These measured spectral energies are related to the temperature of the object using Planck's radiation function:
W(λ,T)=ε*C1 /(λ5 *[exp{C2 /λT}]-1)
W(λ,T)--spectral radiant emittance of object
ε--emissivity of object
λ--wavelength of radiation
T--temperature of object
C1, C2 --constants
Most optical pyrometers are single point devices which provide a temperature that represents a spatial average. Spatial distribution of temperature can be determined only through a series of single point measurements as disclosed in U.S. Pat. No. 4,644,173 assigned to The Babcock & Wilcox Company. In this reference, improvements in spatial resolution were achieved by using optical fibers and photodiode arrays to provide multiple and near simultaneous measurements of temperature. This technique provides improved spatial resolution in temperature measurement, but is limited by the number of simultaneous measurements.
Devices which provide spatially-resolved, two-dimensional temperature maps have been developed. These are of two types: scanning devices which use a single detector in concert with scanning optics that permit measurement of the spatial distribution of spectral energy, and a video camera type which can provide a two-dimensional spectral image.
The sophistication of these devices varies greatly. In some instances, the two-dimensional image of spectral energy is used only to infer regions of hot and cold. With other devices, the temperature at some point in the spectral image must be known (a benchmark) before the two-dimensional temperature map can be determined. Scanning devices have demonstrated the capability to generate two-dimensional temperature maps without the need for this type of benchmarking. All of these devices are analogous to single color pyrometers in that the spatial distribution of intensity is measured at only one wavelength.
An object of the present invention is to provide a video temperature monitor comprising a measurement instrument that yields a real-time display of an object along with a two dimensional temperature map of the object determined using two-color pyrometry.
The components that comprise the invention include an objective lens that collects light from the surroundings for the purpose of forming a focused image, a beam splitter, optical bandpass filters, a path length equalizer, focussing lens, a black and white CCD (charge coupled device) camera, a video digitizer and storage device (frame grabber), a processor, and video displays.
A further object of the present invention is to provide a method of real-time display for an object and a temperature map of the object which is practiced using the apparatus of the invention, and further to provide a measurement apparatus which is simple in design, rugged in construction and economical to manufacture.
The various features of novelty which characterize the invention are pointed out with particularity in the claims annexed to and forming a part of this disclosure. For a better understanding of the invention, its operating advantages and specific objects attained by its uses, reference is made to the accompanying drawing and descriptive matter in which a preferred embodiment of the invention is illustrated.
In the drawing, FIG. 1 is a schematic representation of the measurement apparatus of the present invention.
Referring to the drawing in particular, the invention embodied therein comprises a measurement instrument or apparatus for providing a real-time display of an object 11, for example, a flame or heated area in a furnace or boiler, utilizing an objective lens 12 and a beam splitter 13, along with other optical elements, to form the appropriate displays.
The objective lens 12 provides the function of collecting and focussing light from the object 11 to form an image. The object 11 may be a flame in a furnace with a wall 30 and the image light may pass through a purged sight tube or probe 32. The beam splitter 13 divides the bundle of light rays 10 that pass through the objective lens 12 into two bundles of light rays 10a and 10b. Each light ray bundle will form a real image of the same size. The beam splitter 13 can be of the wavelength division type in which the two ray bundles 10a and 10b are comprised of light of different regions of the wavelength spectrum, or of the intensity division type in which both ray bundles contain the full wavelength spectrum of light but are of only about 1/2 the intensity as the original unsplit ray bundle 10. After the single ray bundle is split into two, the optical axis of the ray bundle 10(b) is directed with a mirror 14 so that the optical axes of the two ray bundles 10(a) and 10(b) are nearly parallel.
One optical bandpass filter 15a and 15b is located in the path of each ray bundle 10a and 10b. Each filter passes light of a specified and different narrow wavelength range and reflects or absorbs all other wavelengths. Filter 15a may pass the sodium 589 nm wavelength, for example, and filter 15b may pass the potassium 768 nm wavelength.
In general, the intensities of the bandpass filtered light in each bundle will not be the same. Depending on the throughput transmission at each wavelength and the temperature of the object, the intensity of the light at the two wavelengths may be substantially different. A neutral density filter 16 placed in the path of highest intensity can have the effect of extending the overall dynamic range of the instrument.
Each of the ray bundles will form a focussed image about their own optical axis. It is a necessary requirement that the two ray bundles form focussed images at the photosensitive surface 20 of a CCD camera 21. However, as a result of splitting and re-directing the optical path of the ray bundle 10(b), the two ray bundles 10(a) and 10(b) will not both form focused images at the photo sensitive surface of the CCD camera sensor. To accomplish this, glass or other material 17 is placed in the path of the ray bundle 10(b) for the purpose of equalizing the optical paths so that two side-by-side focused images are formed at the same surface or plane of the CCD array. This structure is referred to here, as path length compensation means 17.
A lens 18 just upstream of the CCD camera 21 can be used to adjust the size and location of the images on the CCD camera. Since the size of the photosensitive sensor array is fixed, changing the size of the image has the effect of changing the overall field of view of the instrument.
With the optical arrangement described above, the CCD camera 21 will provide two side-by-side images as viewed on a video monitor 23. The gray scale intensity variation in each image represents the spatial variation in spectral energy at the two bandpassed wavelengths. In order to provide better spatial resolution in each of the images, a mask or field stop may be employed in the optical system, for example, as part of lens 18. The purpose of this mask is to prevent overlay of a portion of one of the images on a portion of the second image and to provide a well-defined boundary between the two images.
CCD array cameras are comprised of many individual photosensitive sites called pixels. CCD cameras typically have tens of thousands or hundreds of thousands of individual pixels, with each pixel representing a small area in the object plane. In the invention, each pixel in one of the images has a corresponding pixel in the second image that defines the identical region of space.
The video signal generated by the camera is input to a video digitizer 24 (frame grabber) which serves the purpose of converting the analog video signal (proportional to light energy) from each pixel to a digital value that is stored in computer memory in the digitizer 24 or in processing electronics 25 connected to the digitizer. The digitized picture consists of an array of numerical values proportional to light energy on each pixel in the CCD array.
At each point in the object as defined by a pixel location in each image, the color temperature represented by the energies measured at the two wavelengths can be calculated via two-color pyrometry relationships based on the Planck equation. This can be done in processing electronics 25.
As shown in the figure, the video signal from the CCD camera 21 is displayed on the video screen 23, providing a real-time or "live" display of the object. The digital data that resides in the computer is processed using two-color pyrometry to determine the temperature associated with each pixel location in the image. The resulting two-dimensional, spatially-resolved temperature map can be displayed in many different ways. For example, as a false color temperature map on a second video display 26 in which a defined color scale represents a temperature scale, as a contour plot of isotherms, or as a three-dimensional plot in which two axes represent the two spatial dimensions of the object and the third dimension is temperature.
There are several advantages of the present invention over the prior art.
There are no moving parts in the invention. It is thus not subject to the mechanical breakdown and misalignment of optical scanning devices.
The invention uses solid state detectors for measuring spectral intensities rather than video tubes. A solid state device offers several advantages over tube type video detectors. Solid state devices have a quicker recovery from a saturation condition, less video lag, no burnt-in ghost images resulting from a sustained high intensity image, and less sensitivity to ambient temperature changes.
Other two-dimensional temperature mapping systems use single-color pyrometry, while the present invention uses two-color pyrometry. Two-color pyrometry offers an advantage because spatial variation in the emittance of the object or an intermediate medium that attenuates the signal is not interpreted as variation in temperature as with single-color pyrometry.
The beam-splitting technique of producing side-by-side spectral images on the same photo-detection device is an advantage over images produced on two separate photo-detection devices. The use of a single electro-optic device eliminates sources of differential drift in the offset and gain of the electronics and electro-optics.
With the use of CCD type cameras, variations in the magnitude of the intensity signal can be accommodated without the use of neutral density filters or a variable aperture stop (e.g., an iris). CCD cameras have electronic shuttering capability that can accommodate large changes in signal strength without saturating the photo-diodes in the array. Electronic shuttering also eliminates the spatially variable attenuation common to aperture stops.
Temperature errors caused by time aliasing of the signals from the two spectral images are essentially eliminated. With most single-detector, two-color measurements, the intensity signals at the two wavelengths are measured at different times. Then, changes in the source intensity at frequencies that approach the sampling frequency of the measurement result in errors in the calculated temperature. With the present invention, sampling occurs at video rates, so that the time difference between measurements of the two intensities at a single spatial point is typically less than 70 microseconds.
As described, the CCD arrays in camera 21 are of the silicon photo-diode type. These arrays are inexpensive, readily available, and are sensitive to light with wavelengths up to about 1 micron. CCD arrays fabricated of other materials that are sensitive in different spectral ranges may be advantageous in some applications.
The beam splitting and focussing of the two images may be attained using many different optical components and configurations. These include wavelength division, intensity division, mirrors, and prisms. Also, the order of the optical components need not be the same as indicated in the drawing. For example, the beam splitting and wavelength filtering optics can be located upstream of the objective lens.
The exact location of the bandpass filters is also unimportant, provided the side-by-side images are filtered at the two different wavelengths.
As described, the invention uses one or two lenses to form side-by-side images on the CCD array. The invention may employ multiple lenses (more than three) for the purpose of enhancing the image quality or the field of view of the instrument.
While a specific embodiment of the invention has been shown and described in detail to illustrate the application of the principles of the invention, it will be understood that the invention may be embodied otherwise without departing from such principles.
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Open a share certificate with a minimum balance of USD 500 to earn a fixed dividend rate that is typically higher than a savings or checking account. To earn the full dividend, you are required to keep your funds in the account for the term of your contract. We offer flexible contract periods ranging from 3 to 60 months so you can select the time period best suited to your needs.
If you are unsure when you will need to withdraw your money, you may want to consider a share certificate with a relatively short time period or, alternatively, a Money Market Account (MMA). Keep in mind that unlike a MMA, your dividend rate will remain fixed for the entire term of your contract.
A share certificate earns a fixed dividend rate for the term of your contract. We offer flexible options for how you can invest your dividend earnings, which are credited to you on a monthly basis:
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CPR and Moving Patients
Discussion in 'BLS Discussion' started by Asmo, Aug 30, 2007.
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2-Substituted-4-(4-fluorophenyl)-5-(4-(methylsulfonyl)phenyl)oxazoles or 2-substituted-5-(4-fluorophenyl)-4-(4-(methylsulfonyl)phenyl)oxazoles and derivatives thereof are found to posses significant antiinflammatory activity, especially useful for the treatment of arthritis without deleterious side effects.
1. A compound of the formula (I) ##STR3## wherein X and Y are independently fluoro or methylsulfonyl; and
R is
a) hydrogen;
b) alkyl of from one to ten carbon atoms optionally substituted by hydroxy;
c) alkenyl of from two to ten carbon atoms optionally substituted by hydroxy;
d) alkynyl of from two to ten carbon atoms optionally substituted by hydroxy;
e) cycloalkyl of from 3 to 7 carbons;
f) cycloalkylalkyl wherein cycloalkyl is as defined above and alkyl is of from one to three carbons;
g) aryl which is phenyl, thienyl or 1-, or 2-naphthyl wherein the aryl is optionally substituted by alkoxy of from one to four carbon atoms or halo;
h) aralkyl wherein ar is aryl as defined above and alkyl is of from one to three carbons;
i) diarylalkyl wherein aryl is as defined above and alkyl is of from one to four carbon atoms; or
j) QR1 wherein Q is alkylenyl of from one to four carbon atoms and R1 is COR2 wherein R2 is 1) OR3 wherein R3 is hydrogen or alkyl of from one to four carbon atoms or 2) NR4 R5 wherein R4 and R5 are independently hydrogen and alkyl of from one to four carbon atoms;
or a pharmaceutically-acceptable salt thereof;
provided one of X and Y is methylsulfonyl.
2. A compound of claim 1 wherein X is F and Y is SO2 CH3.
3. A compound of claim 1 wherein X is SO2 CH3 and Y is F.
4. A compound of claim 1 wherein R is phenyl.
5. A compound of claim 1 wherein R is 3-methoxybenzyl, diphenylmethyl or benzyl.
6. A compound of claim 3 which is 5-(4-fluorophenyl)-2-methyl-4-[4-(methylsulfonyl)phenyl]oxazole, 5-(4-fluorophenyl)-4-[4-(methylsulfonyl)phenyl]-2-oxazolepropionic acid or its methyl ester.
7. A compound of claim 2 which is 4-(4-fluorophenyl)-2-(2-phenyl)ethyl-5-(4-(methylsulfonyl)phenyl)oxazole.
8. A compound of claim 2 which is 4-(4-Fluorophenyl)-2-methyl-5-methyl-5-[4-(methylsulfonyl)phenyl]oxazole.
9. A compound of claim 2 which is 4-(4-fluorophenyl)-5-[4-(methylsulfonyl)phenyl]-2-phenyl-oxazole.
10. A compound of claim 2 which is 2-Benzyl-4-(4-fluorophenyl)-5-(4-(methylsulfonyl)phenyloxazole.
11. A compound of claim 2 which is 4-(4-fluorophenyl)-5-[4-(methylsulfonyl)phenyl]-2-(3-phenyl)propyloxazole.
12. A compound of claim 2 which is 4-(4-fluorophenyl)-5-[4-(methylsulfonyl)phenyl]-2-propyloxazole.
13. A compound of claim 2 which is 2-(tertbutyl)-4-(4-fluorophenyl)-5-[4-(methylsulfonyl)phenyl]oxazole.
14. A compound of claim 2 which is 4-(4-fluorophenyl)-2-(4-methoxyphenyl)methyl-5-[4-(methylsulfonyl)phenyl]oxazole.
15. A compound of claim 2 which is 4-(4-fluorophenyl)-2-(3-methoxyphenyl)methyl-5-[4-(methylsulfonyl)phenyl]oxazole.
16. A compound of claim 2 which is 2-diphenylmethyl-4-(4-fluorophenyl)-5-[4-(methylsulfonyl)phenyl]oxazole.
17. A compound of claim 2 which is 4-(4-fluorophenyl)-5-[4-(methylsulfonyl)phenyl]oxazole acetic acid or its ethyl ester.
18. A compound of claim 2 which is 4-(4-fluorophenyl)-5-[4-(methylsulfonyl)phenyl]oxazolepropionic acid or its methyl ester.
19. A compound of claim 2 which is 4-(4-fluorophenyl)-5-[4-(methylsulfonyl)phenyl]oxazolebutanoic acid or its methyl ester.
20. A pharmaceutical composition for the treatment of inflammation which comprises an antiinflammatory amount of the compound of claim 1 and a pharmaceutically acceptable carrier.
21. A method of treating inflammation in a patient suffering therefrom which comprises administering a compound of claim 1 in unit dosage form.
The present invention relates to 4,5-oxazole derivatives and analogs thereof, pharmaceutical compositions containing them and methods of using them to treat inflammation and/or pain in mammals. More particularly, this invention relates to selected 2-substituted-4-(4-fluorophenyl)-5-(4-(methylsulfonyl)phenyl)oxazoles or 2-substituted-5-(4-fluorophenyl)-4-(4-(methylsulfonyl)phenyl)oxazoles having antiinflammatory and/or analgesic activity without erosion of the stomach.
2,3-Diaryl-5-halo thiophenes are disclosed in U.S. Pat. No. 4,590,205 as analgesic or antiinflammatory agents. More particularly, 2,3-diaryl-5-bromo thiophenes are disclosed in U.S. Pat. No. 4,820,827 as having unexpected antiinflammatory and prostaglandin synthetase inhibitory activity for use in the treatment of inflammation and dysmenorrhea. Copending application U.S. Ser. No. 08/004,822 discloses 4-(4-fluorophenyl)-5-(4-methylsulfonylphenyl)thiophene and its 2-substituted bromo analog among its preferred compounds for antiinflammatory activity.
WO/91/19708 discloses thiophenes having various 5-substituents, as well as, 2,3-substitutions having antiinflammatory activity.
U.S. Pat. No. 3,743,656 and U.S. Pat. No. 3,644,399, which is the parent of U.S. Pat. No. 3,743,656, disclose more generically both thiophene and furane derivatives having antiinflammatory activity.
Preparation of a wide-variety of asymmetric biaryl compounds including substituted thiophene, furane and pyrrol rings is disclosed in U.S. Pat. No. 4,990,647 having a suggested utility as precursors for brighteners, pharmaceuticals, plant protection active compounds and liquid crystal materials.
Pyrazole derivatives having antiinflammatory activity are disclosed in European Patent Application Number 90117983.8.
Agents for the treatment of hypertension are disclosed as alkyl-arylimidazole, thiazole and oxazole derivatives in U.S. Pat. No. 4,632,930.
More specifically, U.S. Pat. No. 3,578,671 discloses oxazoles substituted in the 2-position by a saturated or unsaturated aliphatic acid and having 4 and 5 substituents, including phenyl which may be further substituted. French 2156486 of Derwent Abstract No. 41925U-B and U.S. Pat. No. 4,051,250 both generically disclose compounds including 2-oxazolylmercaptoalkanoic acid (esters, amides or cyano derivatives) ring systems having 4,5-diaryl groups which are phenyls both unsubstituted or substituted by a wide variety of substituents and having antiphlogistic, analgesic and antipyretic activity, particularly useful for treating arthritis.
Diarylheterocycles are disclosed in CA114(5):42807w for use as drugs including use against rheumatic and arthritic diseases.
Other related disclosures include U.S. Pat. No. 4,001,228 for antiaggregating activity and U.S. Pat. No. 3,895,024 for intermediates in the production of antiinflammatory agents.
U.S. Pat. No. 4,489,084 describes oxazolyl (or thiazolyl) hydrazinoalkyl nitrile compounds having including two phenyl substituents which phenyls are also further substituted for use as antiinflammatory agents. U.S. Pat. No. 4,143,047 entitled "2-Sulfinyl and 2Sulfonyl Oxazoles" discloses such compounds as reactants to make 2-acylamino oxazole derivatives having antiallergic activity.
Additionally, German Patent No. 3030661 described in Derwent Abstract No. 26458 E/14 provides heteroarylpropargyl ethers as synergists in pesticides, EP 402-246A described in Derwent Abstract 90-370247/50 provides azolyl-substituted alkoxy-acrylate derivatives for use as fungicides and Japanese Patent No. 3014-562 A described in Derwent Abstract No. 91-067958/10 provides alkylene diamine derivatives useful as glutamic acid blockers.
The above references, that disclose antiinflammatory activity, show continuing efforts to find a safe and effective antiinflammatory agent. The novel oxazoles disclosed herein are such safe and also effective antiinflammatory agents furthering such efforts.
The invention compounds are found to show usefulness in vivo as antiinflammatory agents, particularly as antiarthritic agents without ulcerogenic side effects.
This invention relates to novel compounds of the formula (I) ##STR1## and a pharmaceutically acceptable salt thereof; wherein
X and Y are independently fluoro or methylsulfonyl; and
R is 1) hydrogen;
2) alkyl of from one to ten carbon atoms optionally substituted by hydroxy;
3) alkenyl of from two to ten carbon atoms optionally substituted by hydroxy;
4) alkynyl of from two to ten carbon atoms optionally substituted by hydroxy;
5) cycloalkyl of from 3 to 7 carbons;
6) cycloalkylalkyl wherein cycloalkyl is as defined above and alkyl is alkylenyl of from one to three carbons;
7) aryl which is phenyl, 2- or 3-thienyl or 1-, 2- or 3-naphthyl wherein the aryl is optionally substituted by alkoxy of from one to four carbon atoms or halo;
8) aralkyl wherein ar is aryl as defined above and alkyl is alkylenyl is of from one to three carbons;
9) diarylalkyl wherein aryl is as defined above and alkyl is alkylenyl of from one to four carbon atoms;
10) QR1 wherein Q is alkylenyl of from one to four carbon atoms and R1 is COR2 wherein R2 is 1) OR3 wherein R3 is hydrogen or alkyl of from one to four carbon atoms or 2) NR4 R5 wherein R4 and R5 are independently hydrogen and alkyl of from one to four carbon atoms;
The present invention is also a pharmaceutical composition for the treatment of inflammation comprising an antiinflammatory amount of a compound of the formula I together with a pharmaceutically acceptable carrier.
The present invention is also a method of treating a human suffering from an inflammatory disease which comprises administering a compound of the formula of I in unit dosage form.
"Lower alkyl of from one to four" or "ten carbons" in the present invention means methyl, ethyl, propyl, butyl or further pentyl, hexyl, heptyl or the like and isomers thereof respectively.
"Halogen is chloro, fluoro or bromo.
"Lower alkenyl of from two to ten carbons" means ethenyl, 1- or 2-propenyl, 1-, 2- or 3-butenyl and the like and isomers thereof.
"Lower alkynyl of from two to ten carbons" means ethynyl, 1- or 1-propynyl, 1-, 2- or 3-butynyl and the like and isomers thereof.
"Alkylenyl of from one to three" or "to four" is a bridging alkyl chain, i.e. having two open bonds, such as methylenyl, ethylenyl, propylenyl or further butylenyl and isomers thereof.
The compounds of the present invention may contain asymmetric carbon atoms, and, therefore, the instant invention may also include the individual diastereomers and enantiomers, which may be prepared or isolated by methods known to those skilled in the art.
In other words, any resulting racemate can be resolved into the optical antipodes by known methods, for example, by separation of the diastereomeric salts thereof, with an optically active acid, and liberating the optically active amine compound by treatment with a base. Racemic compounds of the present invention can thus be resolved into their optical antipodes e.g., by fractional crystallization of d- or 1-(tartrates, mandelates, or camphorsulfonate) salts.
Additional methods for resolving optical isomers, known to those skilled in the art may be used, for example, those discussed by J. Jaques, A. Collet, and S. Wilen in Enantiomers, Racemates, and Resolutions, John Wiley and Sons, New York (1981).
The compounds I of the invention may preferably be pharmaceutically acceptable salts. Such salts may be basic or acid salts, for example, sodium, potassium, ammonium, calcium, magnesium, acetate, adipate, alginate, citrate, aspartate, benzoate, benzenesulfonate, bisulfate, butyrate, camphorate, camphorate, camphorsulphonate, digluconate, cyclopentanepropionate, dodecylsulfate, ethanesulfonate, glucoheptanoate, glycerophosphate, hemisulfate, heptanoate, hexanoate, fumarate, hydrochloride, hydrobromide, hydroiodide, 2-hydroxyethanesulfonate, lactate, maleate, methanesulfonate, nicotinate, 2-naphthalenesulfonate, oxalate, palmoate, pectinate, persulfate, 3-phenylpropionate, picrate, pivalate, propionate, succinate, tartrate, thiocyanate, tosylate, mesylate, and undecanoate, or phosphate, sulfate, chloride, carbonate and the like. The compounds of the invention are acids, acid derivatives, or when possible basic amines. The basic amines may be used to make acid addition salts of pharmaceutically acceptable weak inorganic or organic acids. These may include such inorganic acids as hydrochloric acid, sulphuric acid and phosphoric acid and such organic acids as oxalic acid, maleic acid, succinic acid and citric acid.
The acid addition salts of said basic compounds are prepared either by dissolving the free base or acid of compound I in aqueous or aqueous alcohol solution or other suitable solvents containing the appropriate acid or base and isolating the salt by evaporating the solution, or by reacting the free base of compound I with an acid as well as reacting compound I having an acid group thereon with a base such that the reactions are in an organic solvent, in which case the salt separates directly or can be obtained by concentration of the solution.
Compounds of the present invention also are meant to include, where possible, hydrated species.
The preferred compounds of the present invention are the compounds of Formula I wherein R is n-propyl, 3-methoxybenzyl, phenyl or diphenylmethyl.
The more preferred compound is of the Formula I wherein R is phenyl.
The procedures utilized in the preparation of the compounds of the formula I of the present invention are essentially that shown by the following Schemes 1 and 2. ##STR2## TBDMSCl is tert-butyl-dimethylsilyl chloride MCPBA is meta-chlorperoxybenzoic acid.
Generally, the above process is carried out as follows:
The synthesis of oxazoles of general formula I (schemes 1 and 2) begins with either 1-(4-fluorophenyl)- 2-[4-(methylthio)phenyl]ethanone or 2-(4-fluorophenyl)1-[4-methylthio)phenyl]ethanone previously described in U.S. Pat. No. 3,647,858. Preparation of the silyl enol ether of this material is followed by oxidation with m-chloroperbenzoic acid to give the appropriate silylated benzoin. Desilylation of this material is achieved using aqueous trifluoroacetic acid to give the desired benzoin. Reaction of the benzoin with the appropriate acid chloride in the presence of pyridine gives the benzoin esters which may be converted to the oxazole upon treatment with ammonium acetate in refluxing acetic acid.
The following examples are not meant to limiting.
Part 1
Preparation of 1-(4-Fluorophenyl)-2-Hydroxy-2-(Methylsulfonyl)Phenyl)Ethanone
A suspension of 2.03 g sodium hydride in 125 mL THF is stirred at 0� C. under a nitrogen atmosphere as a solution containing 20.0 g of 1-(4-fluorophenyl)-2-[4-(methylthio)phenyl]ethanone, as prepared in U.S. Pat. No. 3,647,858, in 100 mL of THF is added dropwise over 30 min. The reaction is allowed to warm to 25� C. for 18 h. The reaction is quenched by pouring into aqueous sodium bicarbonate. The mixture is extracted with ethyl acetate and the combined organic extracts dried over sodium sulfate. Concentration in vacuo provides a yellow oil, which solidified on standing to give 27.9 g of the silyl enol ether. NMR spectra is consistent with the assigned structure. The silyl enol ether is used without further purification.
A solution containing 27.9 g of the silyl enol ether in 500 mL CH2 Cl2 is cooled to 0� C. under a nitrogen atmosphere while being stirred mechanically. 77.1 g of m-chlorperoxybenzoic acid (technical grade, 50-60%) is added and the reaction is stirred at 0� C. for 2 h and allowed to warm to 25� C. over 1 h. The reaction mixture is washed with an aqueous solution of sodium metabisulfite, followed by aqueous sodium bicarbonate. The organic solution is dried over sodium sulfate and concentrated in vacuo to give 24.5 g of 1-(4-fluorophenyl)-2-tert-butyldimethylsilyloxy-2-[4-(methylsulfonyl)phenyl]ethanone. NMR spectra were consistent with the assigned structure. This material is used without further purification.
The benzoin silyl ether is dissolved in 100 mL of 90% aqueous trifluoroacetic acid and stirred at 25� C. for 18 h. The reaction is quenched by slowly pouring into saturated aqueous sodium bicarbonate solution. The product is extracted with ethyl acetate and the combined organic extracts are dried over sodium sulfate. Concentration in vacuo provided an oily solid, which is recrystallized from 50% ethyl acetate-isooctane to give 15.5 g of a crystalline white solid (mp 122-123� C.) whose structure is assigned as 1-(4-Fluorophenyl)-2-Hydroxy-2-(Methylsulfonyl)Phenyl)Ethanone on the basis of its spectral properties.
The isomeric benzoin, 2-(4-fluorophenyl)-2-hydroxy-1-(4-(methylsulfonyl)phenyl)ethanone, is prepared analogously from 2-(4-fluorophenyl)-1-[4-(methylthio)phenylethanone.
Part 2
Preparation of 4-(4-fluorophenyl)-2-(2-phenylethyl)-5-(4-(methylsulfonyl)phenyl)oxazole.
A solution containing 5.00 g of 1-(4-fluorophenyl)-2 -hydroxy-2-(4-(methylsulfonyl)phenyl)ethanone in 100 mL CH2 Cl2 is stirred at 25� C. as 6.60 mL of pyridine is added, followed by 3.61 mL of hydrocinnamoyl chloride.
The reaction is stirred at 25� C. for 48 h, after which the organic solution is washed with 1N HCl, dried over sodium sulfate and concentrated in vacuo to give an oily solid. This material is recrystallized from 50% ethylacetate-isooctane to give 4.40 g of a beige crystalline solid (mp 152�-153.5� C.). NMR spectra are consistent with the assigned structure of 1-(4-fluorophenyl)-2-[4-(methylsulfonyl)phenyl]-2-(2-phenyl)propionyloxy ethanone. This material is dissolved in 100 mL of glacial acetic acid and 7.70 g of ammonium acetate is added. The reaction is heated to reflux with stirring for 1.5 h, after which it is cooled to room temperature and poured into 100 mL of water. The product is extracted with ethyl acetate and the combined organic extracts washed with aqueous sodium bicarbonate, dried over sodium sulfate and concentrated in vacuo to give an oily solid which is recrystallized from 50% ethyl acetate--isooctane to give 3.55 g of a white crystalline solid (mp 117�-118� C.) which is 4-(4-fluorophenyl)-2-(2-phenylethyl)-5-(4-(methylsulfonyl)phenyl)oxazole. NMR spectra is consistent with the assigned structure.
Using appropriate corresponding starting materials the following compounds are prepared in an analogous fashion:
Part 1) 4-(4-Fluorophenyl)-2-methyl-5-[4-(methylsulfonyl)phenyl]oxazole, mp 158�-159� C.
Part 2) 4-(4-Fluorophenyl)-5-[4-(methylsulfonyl)phenyl]-2-phenyloxazole, mp 204�-205� C.
Part 3) 2-Benzyl-4-(4-fluorophenyl) -5-(4-(methylsulfonyl)phenyloxazole, ms m/z 408 (M+H)+.
Part 4) 4-(4-fluorophenyl)-5-[4-(methylsulfonyl)phenyl]-2-(3-phenyl)propyloxazole, ms m/z.
Part 5) 4-(4-fluorophenyl)-5-[4-(methylsulfonyl)phenyl]-2-propyloxazole, ms m/z 436 (M+H)+.
Part 6) 2-(tert-butyl)-4-(4-fluorophenyl)-5-[4-(methylsulfonyl)phenyl]oxazole, mp 130�-131 � C.
Part 7) 4-(4-fluorophenyl)-2-(4-methoxyphenyl)methyl-5-[4-(methylsulfonyl)phenyl]oxazole, mp 123�-124� C.
Part 8) 4-(4-fluorophenyl)-2-(3-methoxyphenyl)methyl-5-[4-(methylsulfonyl)phenyl]oxazole, ms m/z.
Part 9) 2-diphenylmethyl-4-(4-fluorophenyl)-5-[4-(methylsulfonyl)phenyl]oxazole, mp 155�-156 � C.
Part 10) 4-(4-fluorophenyl)-5-[4-(methylsulfonyl)-phenyl]oxazoleacetic acid, ethyl ester, mp 123�-124� C.
Part 11) 4-(4-fluorophenyl)-5-[4-(methylsulfonyl)phenyl]oxazolepropionic acid, methyl ester, ms m/z 404(M+H)+.
Part 12) 4-(4-fluorophenyl)-5-[4-(methylsulfonyl)phenyl]oxazolebutanoic acid, methyl ester, mp 89�-91� C.
Part 13) 5-(4-fluorophenyl)-2-methyl-4-[4-(methylsulfonyl)phenyl]oxazole ms m/z 332 (M+H)+.
Part 14) 5-(4-fluorophenyl)-4-[4-(methylsulfonyl)phenyl]-2-oxazolepropionic acid, methyl ester ms m/z 404 (M+H)+.
The following acids were prepared from their corresponding esters via alkaline hydrolysis using 1N sodium hydroxide in methanol and appropriate reaction conditions.
Part 15) 4-(4-fluorophenyl)-5-[4-(methylsulfonyl)phenyl]-2-oxazoleacetic acid mp 118�-120� C.
Part 16) 4-(4-fluorophenyl)-5-[4-(methylsulfonyl)phenyl]-2-oxazolepropionic acid ms m/z 390 (M+H) +.
Part 17) 4-(4-fluorophenyl)-5-[4-(methylsulfonyl)phenyl]-2-oxazolebutanoic acid. ms m/z 404 (M+H)+.
Part 18) 5-(4-fluorophenyl)-4-[4-(methylsulfonyl)phenyl]-2-oxazolepropanoic acid ms m/z 390 (M+H)+.
Part 19) 4-(4-fluorophenyl)-5-[4-(methylsulfonyl phenyl]-2-(3-hydroxy)propyloxazole is prepared by treating 4-(4-fluorophenyl)-5-[4-(methylsulfonyl)phenyl]-2-oxazolepropanoic acid, methyl ester with diisobutylaluminum hydride. NMR spectra are consistent with the assigned structure, mp 123�-124� C.
Part 20) 4-(4-fluorophenyl)-5-(4-(methylsulfonyl)phenyl)-2-oxazolepropionic amide is prepared by treating 4-(4-fluorophenyl)-5-(4-(methylsulfonyl)phenyl)-2-oxazolepropionic acid, methyl ester with excess ammonia in methanol for 5 days, mp 193�-195� C.
The antiinflammatory agents of this invention can be administered to treat inflammation by any means that produces contact of the active agent with the agent's site of action in the body of a mammal, preferably human. These agents can be administered by any conventional means available for use in conjunction with pharmaceuticals, either as individual therapeutic agents or in a combination of therapeutic agents. The agents can be administered alone, but are generally administered with a pharmaceutical carrier selected on the basis of the chosen route of administration, preferably oral, and standard pharmaceutical practice.
Total daily dose administered to the mammal, preferably human, in single or divided doses may be in amounts, for example, from 0.1 to 100 milligrams per kilogram of body weight. Ordinarily 0.5 to 50, and preferable 1 to 10 milligrams per kilogram per day given in divided doses 1 to 6 times a day or in sustained release form is effective to obtain desired results.
Dosage forms (compositions) suitable for internal administration contain from about 1 milligram to about 500 milligrams of active ingredient per unit. In these pharmaceutical compositions the active ingredient will ordinarily be present in an amount of about 0.5-95% by weight based on the total weight of the composition.
The amount of active ingredient that may be combined with the carrier materials to produce a single dosage form will vary depending upon the host treated and the particular mode of administration.
The dosage regimen to give relief from or ameliorate a disease condition (i.e., treatment) having inflammation as an element of the disease, such as arthritis, or protecting against the further inflammation (i.e., prophylaxis) with the compounds and/or compositions of this invention is selected in accordance with a variety of factors, including the type, age, weight, sex, diet and medical condition of the patient, the severity of the disease, the route of administration, pharmacological considerations such as the activity, efficacy, pharmacokinetics and toxicology profiles of the particular compound employed, whether a drug delivery system is utilized and whether the compound is administered as part of a drug combination. Thus, the dosage regimen actually employed may vary widely and therefore deviate from the preferred dosage regimen set forth above.
The compounds of the present invention may be administered orally, parenterally, by inhalation spray, rectally, or topically in dosage unit formulations containing conventional nontoxic pharmaceutically acceptable carriers, adjuvants, and vehicles as desired. Topical administration may also involve the use of transdermal administration such as transdermal patches or iontophoresis devices. The term parenteral as used herein includes subcutaneous injections, intravenous, intramuscular, intrasternal injection, or infusion techniques.
Injectable preparations, for example, sterile injectable aqueous or oleaginous suspensions may be formulated according to the known art using suitable dispersing or setting agents and suspending agents. The sterile injectable preparation may also be a sterile injectable solution or suspension in a nontoxic parenterally acceptable diluent or solvent, for example, as a solution in 1,3-butanediol. Among the acceptable vehicles and solvents that may be employed are water, Ringer's solution, and isotonic sodium chloride solution. In addition, sterile, fixed oils are conventionally employed as a solvent or suspending medium. For this purpose any bland fixed oil may be employed including synthetic mono- or diglycerides. In addition, fatty acids such as oleic acid find use in the preparation of injectables.
Solid dosage forms for oral administration may include capsules, tablets, pills, powders, and granules. In such solid dosage forms, the active compound may be admixed with at least one inert diluent such as sucrose lactose or starch. Such dosage forms may also comprise, as in normal practice, additional substances other than inert diluents, e.g., lubricating agents such as magnesium stearate. In the case of capsules, tablets, and pills, the dosage forms may also comprise buffering agents. Tablets and pills can additionally be prepared with enteric coatings, if necessary.
Liquid dosage forms for oral administration may include pharmaceutically acceptable emulsions, solutions, suspensions, syrups, and elixirs containing inert diluents commonly used in the art, such as water. Such compositions may also comprise adjuvants, such as wetting agents, emulsifying and suspending agents, and sweetening, flavoring, and perfuming agents.
Pharmaceutically acceptable carriers encompass all the foregoing and the like.
While the compounds of the invention can be administered as the sole active pharmaceutical agent, they can also be used in combination with one or more immunomodulators, antiviral agents or other antiinfective agents. For example, the compounds of the invention can be administered in combination with antihistamines or with other such agents known heretofore to be effective in combination with antiinflammatory agents. When administered as a combination, the therapeutic agents can be formulated as separate compositions which are given at the same time or different times, or the therapeutic agents can be given as a single composition.
The foregoing is merely illustrative of the invention and is not intended to limit the invention to the disclosed compounds. Variations and changes which are obvious to one skilled in the art are intended to be with in the scope and nature of the invention which are defined in the appended claims.
The examples herein can be repeated with similar success by substituting the generically or specifically described reactants and/or operating conditions of this invention for those used in the preceding examples.
The antiinflammatory utility of the compounds of the present invention is shown by an assay essentially performed in an animal model using a procedure recognized to show antiinflammatory activity. See Winter et al in "Carrageenan-induced Edema in Hind Paw of the Rat" Proc. Soc. Exp. Biol. Med., 111, 544, 1962.
The IC50 shows the % decrease from control paw volume determined in this procedure and the data for a selected compound in this invention is summarized in Table 2.
TABLE 2______________________________________ Rat Paw ED40 mg/kg______________________________________Example 1Part 2 5______________________________________
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