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Britannia's Mercies, and Her Duty, Considered in Two Discourses, Delivered in the Methodist Chapel, at Halifax, on Thursday, November 29, 1798, ... by Thomas Taylor, V.D.M. book by Thomas Taylor | 1 available editions | Alibris Books
Britannia's Mercies, and Her Duty, Considered in Two Discourses, Delivered in the Methodist Chapel, at Halifax, on Thursday, November 29, 1798, ... by Thomas Taylor, V.D.M
The 18th century was a wealth of knowledge, exploration and rapidly growing technology and expanding record-keeping made possible by advances in the printing press. In its determination to preserve the century of revolution, Gale initiated a revolution of its own: digitization of epic proportions to preserve these invaluable works in the largest archive of its kind. Now for the first time these high-quality digital copies of original 18th century manuscripts are available in print, making them highly accessible to libraries, undergraduate students, and independent scholars.The Age of Enlightenment profoundly enriched religious and philosophical understanding and continues to influence present-day thinking. Works collected here include masterpieces by David Hume, Immanuel Kant, and Jean-Jacques Rousseau, as well as religious sermons and moral debates on the issues of the day, such as the slave trade. The Age of Reason saw conflict between Protestantism and Catholicism transformed into one between faith and logic -- a debate that continues in the twenty-first century.++++The below data was compiled from various identification fields in the bibliographic record of this title. This data is provided as an additional tool in helping to insure edition identification: ++++British LibraryT116743The final leaf contains a hymn and advertisements.Leeds: printed by Binns and Brown, 1799. 30, [2]p.; 12 Read Less
ISBN-13: 9781140666585
ISBN 1140666584
ISBN-13 9781140666585
Alibris ID 10939568624
Alibris ID 13403986899
The Two Covenants of God with Mankind: Or, the Divine Justice and Mercy Explain'd and Vindicated in an Essay, ... by Tho. Taylor, ...
The Progresse of Saints to Full Holinesse Described in Sundry Apostolicall Aphorismes, or Short Precepts Tending to Sanctification, with a Sweete and Divine Prayer to Attaine the Practise of Those Holy Precepts / By Thomas Taylor ... (1630)
A Loving Exhortation to All Kings, Princes, Potentates, Bishops and People in the Whole Christendom Wherein Is a Distinction Betwixt the True and False Teachers ... / Written by Thomas Taylor. (1666)
Redeeming Grace Displayed to the Chief of Sinners; Being a Short Account of God's Dealings with Thomas Taylor. ... the Third Edition.

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The Ultimate Code Book: 2001 Edition: Amazon.co.uk: Prima Development: Books
The Ultimate Code Book: 2001 Edition [Paperback]
Publication Date: Jan 2001 The Ultimate Code Book is now right at your fingertips! Get the best weapons, endless ammo, unlimited lives and infinite health codes in The Ultimate Code Book, 2001 Edition from Prima. This is Prima's biggest code book ever! With over 30,000 codes and secrets for the PlayStation, Nintendo 64, Game Boy, Dreamcast, PC–and now PlayStation 2–you'll be invincible. Make Prima your code source!
The Ultimate Code Book is now right at your fingertips! Get the best weapons, endless ammo, unlimited lives and infinite health codes in The Ultimate Code Book, 2001 Edition from Prima. This is Prima's biggest code book ever! With over 30,000 codes and secrets for the PlayStation, Nintendo 64, Game Boy, Dreamcast, PC–and now PlayStation 2–you'll be invincible. Make Prima your code source!
Publisher: Prima Games (Jan 2001)
ISBN-10: 076153475X
ISBN-13: 978-0761534754
Amazon Bestsellers Rank: 7,178,742 in Books (See Top 100 in Books)
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View upcoming funeral services, obituaries, and funeral flowers for Cappadona Funeral Home in Colorado Springs, CO. Find contact information, view maps, and more.
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William was born on August 21, 1925 and passed away on Friday, October 20, 2017. William was a resident of Colorado at the time of passing.
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This page contains text from Wikipedia, the Free Encyclopedia -	https://wn.com/Harrison_City,_Pennsylvania
Latest News for: harrison city
46 minutes ago. Renee Aiken loved to take weekend car rides with her dad, Richard Davis. That is, when he wasn’t on a motorcycle ride or on weekend excursions with his wife, Mary Ann ... Richard A. Davis of Penn Township died Wednesday, Aug. 14, 2019. He was 75 ... Mr ... Mr ... Mr ... Mr ... Sunday at the Lindsay-Jobe Funeral Home, 3343 Route 130, Harrison City ... News ....
A grieving man’s cry for support draws people from all over to mourn El Paso ...
Then she became one of the 22 slain in the race-driven massacre at Walmart, the worst in the city's history ... Fearful he'd be alone, he'd invited the entire city join him ... Basco, for his wife and city." ... Basco remains for many an enigma and a symbol of the city's pain. Harrison ......
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This is a community calendar ... Inclusion of items is at the discretion of the newspaper ... Assistance ... Albany Planning Commission, 5.15 p.m., council chambers, City Hall, 333 Broadalbin St ... Corvallis City Council, 6 p.m., council chambers, downtown fire station, 400 NW Harrison Blvd ... (men’s meeting), Zion Lutheran Church, 2745 NW Harrison Blvd., Corvallis....
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6 to the Harrison City Council ... Walker has also differed with members of the Harrison City Council over a proposal to extend sewer service to a new development....
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Extended Stay America - Bloomington - Normal (IL) - Hotel Reviews - TripAdvisor
> Extended Stay America - Bloomington - Normal
1805 S Veterans Pkwy, Bloomington, IL 61701 Hotel amenities
English first Any hnpasha
Very nice peaceful. The room was clean and comfortable. Since I stayed for many weeks, The hotel service desk helped me keeping one of my bag everytime I went away for the weekend. That was nice, and it saved me from carrying extra bags for my flights over the weekend. The Morning coffee/tea with little something eat was a bonus...
Manager_11525, General Manager at Extended Stay America - Bloomington - Normal, responded to this review
Thank you so much for sharing your experience with us. I am proud of our team for providing you with a peaceful and positive experience while you stayed at our hotel. We were happy to assist you as needed, including holding your luggage over the weekends.
Thank you again for your kind words. The staff and I would love to...
More mountainfella
“It took 35 minutes to check in... and it was wrong!”
We recently stayed here on a trip from Wisconsin down to Branson, MO. As a traveling group of musicians we thought this would be a great place to stay for the night, and booked online at expedia. We finished a show in Wisconsin and drove straight to the hotel, arriving at 1:20am. The rooms had already been booked and fully...
I received a copy of your review, and wanted to take a moment to personally respond. The situation you described regarding the first impression of our hotel, dealing with the front entrance door, and the time it took to get you checked in, is truly regrettable. We are very sorry for your experience. To prevent this from happening again, my...
More Travelers are raving about these Bloomington hotels
This hotel is a good option for those who would want to stay for a few weeks and as such it is a little different than other hotels. It offers various services such as internet, breakfast, and others. I was only bothered by the lack of cleanliness of the hall way carpets and the hall areas. The room itself was...
See 2 more reviews by TravelWorldSeeWithin for Bloomington Region39, Manager at Extended Stay America - Bloomington - Normal, responded to this review
We know that you have several lodging options, which is...
We stayed here one night. Overall it was a nice stay. It was very quiet in our room. My husband and I both commented the next morning on how quiet it was. Our tv quit working but Margarita at the front desk came right up and resolved the problem. I would have preferred a better breakfast option then just the...
Region39, Manager at Extended Stay America - Bloomington - Normal, responded to this review
Thank you for taking the time to write a review of your stay. I'm so pleased to hear that you had a quiet and peaceful stay. Also glad to hear that Margarita was able to fix your TV problem. Thank you again for sharing your experience with us. We look forward to welcoming you back in the future!
More Balamurali S
It was a nice experience for me staying at this hotel for 2 weeks. The staff is very helpful and friendly. Rooms are very clean with all the needed amenities. During my stay I came to know that I have made 2 reservations by mistake and so the booking charges were deducted on both the reservations. When I contacted Staff...
Thank you for your great review of our property. I'm so pleased to hear that the staff was responsive to your needs, and were able to help you with your reservations. It was also good to hear that your room was FRESH and clean and you had everything you needed. Thank you again for sharing your experience with us. We...
From reservation to checkout everything was easy, as promised and done with a smile.
Anything and everything I needed or asked for was done promptly.
I would highly recommend this location. I was without a printer and I could email documents to the manager and they would print it out for me. I could then sign it and then they...
This hotel is a very nice place to stay. It was great to have a quick breakfast to be able to grab before going to work. The staff is very friendly and helpful. The housekeeping was great and my room was always cleaned. I was assisted with my questions and whatever else I needed.
Thank you so very much, Angela for your nice review of our property. Whenever I read comments like yours, it always gives me such great pleasure. My entire staff strives to make every guest's stay totally enjoyable, and our greatest reward is validation that we've done just that. As a member of the Extended Stay Hotels(sm) family, we are proud...
More PallsM
I stayed here for a month. The rooms are good sized and with kitchen and all the amenities, it almost feels like home. The staff are all very efficient and helpful. They made my stay very comfortable and I couldn't ask for more specially at the low per night rates that they have. But the highlight of my stay was...
More DurgaV
The price is value for money. The staff are very good and helpful. Wonderful support from management. Feel like home. They have introduced complimentary breakfast recently to increase the value to the customer. They take care of customers very well. I would recommend to any of the friends. it would be helpful if they had fitness centre, restaurant and free...
I appreciate you taking the time to write a review of your experience with us. We continually work to improve our hotel, so I really appreciate your positive comments. It reinforces that we are working towards our Goal of EXCELLENCE; Every Day in Every Way. I invite you to contact me at kcesario@extendedstay.com if you have any additional comments. I...
More derail130
“Average now but think better soon”
The price is good and convenient to where I am currently working, about a three minute trip. Have read some of the reviews. Yes there is a curry smell in the halls. Not in the room though. Carpet is terrible in the hallways. But I know Extended Stay is in the process of remodeling. I stayed in New Jersey last...
I appreciate you taking the time to write a review of your experience with us. I sincerely apologize that we have had some problems with the upgrade timelines. In response to your feedback, I am contacting our TV supplier to get a new delivery date for our TVs. We continually work to improve our hotel, so I really appreciate your...
Great value on a similar hotel Hawthorn Suites by Wyndham Bloomington Bloomington, IL 179 Reviews Still looking for a hotel? Highly rated hotels in Bloomington
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Hotel Style: Ranked #13 of 24 hotels in Bloomington
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Free Guide to Bloomington Get your guide to the top local hotels, restaurants and things to do Extended Stay America - Bloomington - Normal Photos (10 traveler photos) Hotels around Bloomington
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One Good Turn: A Natural History of the Screwdriver and the Screw: Witold Rybczynski: 9780002000314: Amazon.com: Books
Books Advanced Search New Releases Best Sellers The New York Times® Best Sellers Children's Books Textbooks Textbook Rentals Sell Us Your Books Best Books of the Month Deals in Books One Good Turn
– December 5, 2005
Hardcover, December 5, 2005
7 New from $44.30
2 Collectible from $28.89
39 New from $3.86
Mass Market Paperback from $6.75
The Best Tool of the Millennium The seeds of Rybczynski's elegant and illuminating new book were sown by The New York Times, whose editors asked him to write an essay identifying "the best tool of the millennium." An award-winning author who once built a house using only hand tools, Rybczynski has intimate knowledge of the toolbox -- both its contents and its history -- which serves him beautifully on his quest. One Good Turn is a story starring Archimedes, who invented the water screw and introduced the helix, and Leonardo, who sketched a machine for carving wood screws. It is a story of mechanical discovery and genius that takes readers from ancient Greece to car design in the age of American industry. Rybczynski writes an ode to the screw, without which there would be no telescope, no microscope -- in short, no enlightenment science. One of our finest cultural and architectural historians, Rybczynski renders a graceful, original, and engaging portrait of the tool that changed the course of civilization.
Paperback$10.41 Prime The Evolution of Useful Things: How Everyday Artifacts-From Forks and Pins to Paper Clips and Zippers-Came to be as They are
Paperback$12.45 Prime How To Run A Lathe: For The Beginner: How To Erect, Care For And Operate A Screw Cutting Engine Lathe
Paperback$5.36 Prime Why We Make Things and Why It Matters: The Education of a Craftsman
Paperback$14.75 Prime Coal: A Human History
In 1999, an editor of the New York Times Magazine approached Witold Rybczynski, the well-known student of architecture and urban design, and asked him to write a short essay on the best and most useful common tool of the past millennium. Rybczynski took the assignment, but when he began to look into the history of the items in his workshop--hammers and saws, levels and planes--he found that almost all of them had pedigrees that extended well into antiquity. Nearly ready to admit defeat, he asked his wife for ideas. Her answer was inspired: "You always need a screwdriver for something." True enough. And, Rybczynski discovered, the screwdriver is a relative newcomer in humankind's arsenal of gadgetry, an invention of the late European Middle Ages and the only major mechanical device that the Chinese did not independently invent. Leonardo da Vinci got to it early on, of course, as he did so many other things, designing a number of screw-cutting machines with interchangeable gears. Still, it took generations for the screw (and with it the screwdriver and lathe) to come into general use, and it was not until the modern era that such improvements as slotted and socket screws came into being. Rybczynski's explorations into that lineage, here expanded to book length, are highly entertaining, and sure to engage readers interested in the origins of everyday things. --Gregory McNamee --This text refers to an out of print or unavailable edition of this title.
Acclaimed hardware, household and landscape writer Rybczynski invites readers to see how the world got screwedAand why it took so long, and how it felt. Romans had most of our hand tools, though cranks are medieval; screws and screwdrivers, however, originatedAwhen? Scottish crafts manuals from around the time of the American Revolution give screwdrivers as "turnscrews"; the same word in French, tournevis, turns up in 1723. Even earlier, screws appeared as a spinoff from Renaissance warfare, keeping the parts of a matchlock rifle linked. Used in timepieces and armaments, the screws of the 16th century were hand-cutAboth expensive and unreliable. Efficient, widespread screwing required (a) more uses, to up the demand; (b) steam power, aka the Industrial Revolution; and (c) smart mechanics and engineers, who invented the manufacturing procedures that Rybczynski describes. Canada's Peter L. Robertson came up with the wondrous socket-head (square-holed) screw; the inferior Phillips (+-holed) head came later, but became standard outside Canada. Siege engines, early firearms like the arquebus, 19th-century child labor, the precision lathe, door hinges and the great minds of ancient Greek geometry also figure among the threads of Rybczynski's tightly wound exposition. A professor of urbanism at the University of Pennsylvania, Rybczynski began this book after the New York Times asked him to pick the Tool of the Millennium. The short volume can feel like a bagatelle compared to Rybczynski's most ambitious projectsAhis biography of Frederick Law Olmsted, A Clearing in the Distance, or the endeavor (chronicled in his Home) of building his own house plank by plank. Nevertheless, Rybczynski's many fansAand those who care for the history of hardwareAwill want to stick their heads in his new book: many will find themselves fastened to its story. (Sept.) Copyright 2000 Reed Business Information, Inc.
Start reading One Good Turn on your Kindle in under a minute.
Publisher: HarperCollins Canada (December 5, 2005)
ISBN-10: 0002000318
ISBN-13: 978-0002000314
Product Dimensions: 7.6 x 5.5 x 0.4 inches
Amazon Best Sellers Rank: #3,341,429 in Books (See Top 100 in Books)
#208 in Books > Crafts, Hobbies & Home > Home Improvement & Design > How-to & Home Improvements > Hand Tools
#456 in Books > Crafts, Hobbies & Home > Home Improvement & Design > How-to & Home Improvements > Power Tools
#3608 in Books > Crafts, Hobbies & Home > Home Improvement & Design > How-to & Home Improvements > Woodworking > Projects
69 of 73 people found the following review helpfulScrew Up Your Courage and Dive into Screwdrivers!
HALL OF FAMETOP 1000 REVIEWERVINE VOICE on August 28, 2000Format: Hardcover
Although I had no interest in screwdrivers and screws when I started this book, the text provided a pleasant reading experience and I learned more than I thought I would. All in all, it was well worth the time spent. I think you will feel that way too, unless you have no interest at all in mechanical devices and the process of innovation. My favorite parts related to the innovations.This book is composed of equal parts (1) why the author chose the screwdriver as the tool of the millennium for his article in the Sunday New York Times Magazine (2) where you have to go to find out about screwdrivers from the past (3) how he developed the information for this history of the screwdriver and screws and (4) the geniuses who developed the key advances in the technology of these useful devices. The style is a bit rambling, much like what would happen if you were chatting about the subject over a barbecue in the back yard with plenty of time on your hands. I can assure you this must be the most complete and authoritative book about screwdrivers and screws ever, especially since the author points out the virtual absence of any prior material turning up in his research.Let me summarize the key areas. He picked the screwdriver as the tool of the millennium not because he thought of it, but because his wife told him that it was the one tool that she always kept around. After having gone through his own tool kit, he had not even thought of the screwdriver.The first place where much shows up on the screwdriver in older texts is Diderot's Encyclopedia. In those days screwdrivers were called turnscrews.To get a flavor of the screwdriver in the middle ages, when it seems to have appeared, you have to look into armor and early guns.Read more ›
22 of 23 people found the following review helpfulOne Good Turn Deserves to be read.
Walter J. Maslowski
Let's get the main question out of the way: Can an entire book devoted to the history of the screw and screwdriver possibly be worth reading? The answer is an unqualified yes. This small book takes an unusual, almost reverential, look at the the nature of tools and the mind of the inventor and innovator. Rybczynski recounts his research into the origins of this ubiquitous tool, so it is also a tale of the research process. He tells the story in a casual, personal style, making it an easy read. The book is not tightly focused on its subject, filled with many digressions and asides which are as interesting as the main narrative. One of my favorites concerns the invention of the the shirt button. It seems like the epitome of simplicity, and could have been made thousands of years ago, yet it took until the 1300's for some unknown genius to make the "leap of imagination" and conceive of the device, which seems simple but is not at all intuitive. The author asks the reader to imagine trying to explain the the "twist and flip" motion to some one who has never used one. Its nuggets like this, which make the reader look at common items from an entirely different perspective, that makes the book shine. It turns out that one of the first uses of the screw dates back to the Middle Ages, as a method of fastening the the brutally abused armor of jousting knights, and later to secure the matchlock mechanisms of the earliest firearms. However, in exploring the concept of the helix, the basis of the screw, the author reaches much further back in time, to the ancient Greeks, Romans and Egyptians, who understood the shape and put it to use in irrigation and wine presses.Read more ›
17 of 19 people found the following review helpfulAn Essay Puffed Up
on December 11, 2000Format: Hardcover
The book is made up of about 10 pages of the history of the screw/screwdriver, 15 pages of the author's frustrating research (his frustration, not the reader's), and 120 pages of filler. Much of the filler is interesting but Rybczynski struggled hard, and wandered far, to find enough words to fill this very slim book (probably only 20,000 words). Since less than 10% is about the subject, the substance isn't quite enough for a solid magazine article. I wanted, and expected, more. I'm sure Rybczynski's editor did, too. Given the author's academic profession, I would think the book was the product of the "Publish or perish" syndrome were it not for his considerable resume of published books. I suspect that Professor Rybczynski, were he to read this review, might acknowledge that he was caught.
12 of 13 people found the following review helpfulif Bob Vila and James Burke had a son
TOP 500 REVIEWER on November 30, 2001Format: Paperback
A New York Times editor asked Mr. Rybczynski to write an article about his choice for best tool of the millennium. One would think that this would involve deciding on a tool, researching its history and uses, and writing it up. But that would be too linear. Instead, the author takes us on a rambling walk through the toolbox. We learn not only about the development of many tools and machines (adze, augur, hammer, lathe, gears and presses), but about the scientists and inventors, even financiers, who contributed to the development of the screwdriver, and the applications (early firearms and clocks) that helped (literally) shape the device. We learn about the Phillips versus the Robertson screw, and the limitations of earlier lathes, which led to the first screws being handmade. Many interesting facts like this entertain and inform.As a librarian I appreciated the author's friendly discussion of the references he found useful for his research. There are many black-and-white line drawings to help you visualize the items being discussed, as well as a notes section, a good index, and illustration credits.Weaknesses: I would have liked to have read a brief discussion of the (seven?) Simple Machines, as I think many were discussed here, and it would have been an interesting reminder of things from physics class that I've forgotten. In addition, I looked up a quote by Plutarch in the Notes section, and the citation began "Quoted by E. J. Dijksterhuis .... " with no information about the actual source -- not much help!This was a fun read. If you are the kind of person who enjoys browsing through the dictionary or a bookstore, you will probably enjoy this little gem of a volume by this handyman-storyteller.Highly recommended.
I enjoyed this book very much. I love microhistories. It didn't have to be the length of War and Peace for me to enjoy the content.
Arrived on time and just a described.
Published 9 months ago by Denise Heckman
Published 14 months ago by Eileen
A good book on an overlooked subject, but incomplete. It goes into the history of the screw, and screwdrivers, but leaves out it's relatives, the bolts and nuts, taps, and a good...
Published 16 months ago by o. migillicuddy
A well written quick reading book, One Good Turn is as much a detective story as a history. The author describes his search for the origins of the common screwdriver and the screw...
Published 17 months ago by Branson
I bought this as a gift and have not read it myself. Dad said it explained far more about the history of tools than he'd expected, and he was enthusiastic about the book.
Published 18 months ago by Ellyn Ritterskamp
One Good Turn is a True Gem, I love it
By: RevitWithold Rybczynski: One Good Turn: A Natural History of the Screwdriver and the Screw. I can't give it enough praise.
Published 20 months ago by revit
If you are an engineer or simply someone who is fascinated by the stories behind the everyday things in life, then you will enjoy this book.
Published on May 5, 2013 by Craig E. Dupler
This is simply a wonderful book, very well researched and entertaining to read. If you know anyone interested in technical things, science, and/or social history get them this...
Published on February 11, 2013 by Jim
Blah with patches of delight
Overall it reads sleepily. However I did enjoy the second half of the book more, it just takes a long time for the author to cut to the chase.
Published on October 23, 2012 by Zaylor
$11.42 Prime Homebuilding and Woodworking in Colonial America (Illustrated Living History Series)
$11.30 Prime How Architecture Works: A Humanist's Toolkit
$10.41 Prime City Life


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The Philadelphia Chromosome: A Mutant Gene and the Quest to Cure Cancer at the Genetic Level by Jessica Wapner, Hardcover | Barnes & Noble
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BBC One - Doctor Who, Series 7 Part 1, The Power of Three We use cookies to ensure that we give you the best experience on our website. We also use cookies to ensure we show you advertising that is relevant to you. If you continue without changing your settings, we'll assume that you are happy to receive all cookies on the BBC website. However, if you would like to, you can change your cookie settings at any time. Continue Find out more ]]> Accessibility links Skip to content Skip to local navigation Accessibility Help BBC iD BBC iD Settings Sign out bbc.co.uk navigation News Sport Weather Travel Culture Autos TV Radio More… Search term: BBC OneDoctor Who
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Patent US6518397 - Pharmaceuticals for modulating hormone responsiveness - Google Patents
This invention relates to isolated and purified proteins, such as calreticulin and mimetics and inhibitors of calreticulin, for a novel use of modulating hormone responsiveness. These proteins are useful in gene therapy and in manufacturing pharmaceuticals for treating a variety of diseases, including...http://www.google.com/patents/US6518397?utm_source=gb-gplus-sharePatent US6518397 - Pharmaceuticals for modulating hormone responsiveness
Publication number US6518397 B1
Application number US 08/900,241
Also published as CA2298930A1, EP1001986A2
Publication number 08900241, 900241, US 6518397 B1, US 6518397B1, US-B1-6518397, US6518397 B1, US6518397B1
Inventors Shoukat Dedhar
Original Assignee Shoukat Dedhar
Patent Citations (8), Non-Patent Citations (58), Referenced by (3), Classifications (21), Legal Events (4)
Pharmaceuticals for modulating hormone responsiveness
US 6518397 B1
1. An isolated and purified peptide of 6 to 100 amino acids comprising the amino acid sequence KXFFKR wherein X is G, A or V (SEQ ID NO:68), with the proviso that the prptide is not KGFFKR, KAFFKR, KVFFKR or Ac-SCEGCKAFFKRS-[3H]I-OG (SEQ ID NO:70), and wherein the peptide binds calreticulin.
A By way of example, the amino acid sequence of the DNA binding domains of RAR (SEQ ID NO:8), RXR (SEQ ID NO:5), T3Rβ (SEQ ID NO:2), VDR (SEQ ID NO:2), GR (SEQ ID NO:3), MR (SEQ ID NO:3), AR (SEQ ID NO:3), ER (SEQ ID NO:4) and Integrin α subunits (SEQ ID NO:9) are set out below:
Calreticulin binds to nuclear hormone receptors by interacting with the amino acid sequence [SEQ ID NO:1] KXFFX1R. The interaction results in a profound inhibition of nuclear hormone receptor DNA binding activity which can be reversed by soluble competing synthetic peptides.with the generic sequence KXFFX1R [SEQ ID NO:1]. The inhibition of DNA binding by calreticulin can also be reversed by an antibody to or inhibitor of calreticulin. Transient or stable overexpression of calreticulin by cDNA transfection also results in the inhibition of nuclear hormone receptor induced gene transcriptional activity. Furthermore, decreased expression of calreticulin by stable transfection of antisense calreticulin cDNA results in increased sensitivity of the cells to hormones due to the increased transcriptional activity of the nuclear hormone receptor.
AMINO ACID ONE LETTER ABBREVIATION
Typtophan W
Integrins* Steroid Nuclear Receptors
a1 KIGFFKR [SEQ ID NO:11] RARa ACEGCKGFFRRSIQK [SEQ ID NO:18]
a2 KLGFFKR [SEQ ID NO:7] T3Rb TCEGCKGFFRRTIQK [SEQ ID NO:19]
a3 KCGFFKR [SEQ ID NO:12] VDR TCEGCKGFFRRSMKR [SEQ ID NO:20]
a4 KAGFFKR [SEQ ID NO:13] GR TCGSCKVFFKRAVEG [SEQ ID NO:21]
a5 KLGFFKR [SEQ ID NO:7] MR TCGSCKVFFKRAVEG [SEQ ID NO:21]
a6 (A) KCGFFKR [SEQ ID NO:12] AR TCGSCKVFFKRAAAG [SEQ ID NO:22]
a6 (B) KCGFFKR [SEQ ID NO:12] PR TCGSCKVFFKRAMEG [SEQ ID NO:23]
a7 KLGFFKR [SEQ ID NO:7] ER SCEGCKAFFKRSIQG [SEQ ID NO:24]
a8 (chick) KCGFFDR [SEQ ID NO:14] RXR SCEGCKGFFKRTVRK [SEQ ID NO:25]
av RMGFFKR [SEQ ID NO:15] Steroid receptor TCEGCTGFFKRSIRK [SEQ ID NO:26]
Mac-1 KLGFFKR [SEQ ID NO:7] Nerve growth TCEGCKGFFKRTVQK [SEQ ID NO:27]
p150 KVGFFKR [SEQ ID NO:16] Early response TCEGCKGFFKRTVQK [SEQ ID NO:27]
PS2 KCGFFNR [SEQ ID NO:17] Chorion Factor SCEGCKGFFKRTVRK [SEQ ID NO:25]
(Drosophila) 1
As described in Rennie et al., 1993, DNA binding domain of recombinant rat androgen receptor was prepared as a GST-fusion protein using the pGEX-3X vector and purified by glutathione-agarose affinity chromatography. p60 (calreticulin) was purified by affinity chromatography on KLGFFKR-sepharose [SEQ ID NO:7], followed by gel electrophoresis as described in detail in Rojiani et al., 1991. Purified AR and p60 (calreticulin) were found to be greater than 90% and 95% pure, respectively, as determined by SDS-PAGE and Coomassie Blue staining. Recombinant calreticulin (GST-fusion protein) was prepared as described by Baksh and Michalak, 1991. Gel retardation assays were carried out as described by Rennie et al., 1993. To analyze the effect of p60, or recombinant calreticulin, on receptor-DNA binding activity, the AR was pre-incubated with p60 for 30 min at 4° C. To analyze the effects of synthetic peptides, anti-calreticulin antibody, and non-immune IgG on p60 inhibition of AR-ARE binding, the peptide, antibody or IgG were pre-incubated with p60 for 30 min at 4° C. The androgen receptor preparation was then added to these mixtures and further incubated for 30 min at 4° C.
Affinity purified DNA binding domain of the recombinant rat androgen receptor (AR) was pre-incubated with or without the indicated concentrations of purified p60 at 4° C. for 30 min. After this pre-incubation the reaction mixtures were incubated with 32P-labeled 26 base pair ARE (Rennie et al., 1993) (androgen response element), and analyzed by gel retardation assay. The sequence of the ARE used was [SEQ ID NO:28]:
The level of calreticulin expression was estimated by Western blot analysis of cellular lysates (Rojiani et al., 1991) followed by densitometric scanning. For Northern blot analysis total cellular RNA (15 μg) from the indicated cell lines was hybridized to 32-P-labeled CRABP(II) cDNA (Giguere et al., 1990) at 65° C. using Rapid Hyb buffer (Amersham Corp.). The blot was stripped and reprobed with a mouse actin cDNA probe to check for equal loading of RNA. Values for relative mRNA levels were derived from quantitation of the signal in each lane using a Molecular Dynamics Phosphorimager. CRABPII mRNA levels were normalized against the corresponding actin mRNA signal.
Cells were stained with anti-class III β tubulin antibody (TuJi) followed by FITC conjugated secondary antibody as described above. A and B: P19 (neo) EC cells; C and D: P19-Cal-1 EC cells; E and F: P19 Cal-2 EC cells. A, C and E; untreated cells. B, D and F: 6 days at RA (0.5 μM) treated cells. The cells were visualized using a Zeiss Axioscop microscope under oil immersion and photographed with Kodak T-Max 400 film. Magnification 100×.
Cell culture conditions: Mouse embryonic carcinoma (P19) cell, grown in 60 mm dishes in 7.5% donor calf serum, 2.5% fetal calf serum alpha MEM (Gibco/BRL) were treated with the peptides KLGFFKR [SEQ ID NO:7] or KLRFGFK [SEQ ID NO:29] for three hours or overnight for 20 hours at 37° C., 5% CO2. With few exceptions, KLXFFKR [SEQ ID NO:31] is the peptide sequence specific within the binding domain of all steroid receptors. KLRFGFK [SEQ ID NO:29] is the scrambled peptide of the above sequence. Subsequently each plate was washed four times with serum free alpha MEM to remove excess peptides and replenished with fresh serum containing media. Cells were then transfected by standard calcium phosphate precipitation method (Current Protocols in Molecular Biology 9:1) with 1 microgram bRARE in pTKluc, 1.5 microgram pRSV bgal, 3 microgram pKS (carrier) per 60 mm dish. Following a 16 hour incubation at 37° C. 5% CO2, each plate was washed two times with serum free alphaMEM and replenished with serum containing media supplement with 107 M retinoic acid (Sigma R2625) and 800 microgram/ml G418 (Gibco 1181-031). Following another 24 hours incubation cells were washed three times with PBS and each 60 mm dish of cells was lysed in 100 microliters of 1 % triton X100, 100 mM KPO4 pH7.8, 1 mM DTT. Cell lysates were stored at −70° C. Prior to luciferase/bgal assays, cell debris were spun out on an Eppendorf microfuge (5415C) at 4° C. full speed for 20 minutes.
Beta-gal assay: Assay was done in a microtitre plate (Linbro 76-232-05). Ten microliters of cell lysate were mixed with 90 microliters of bgal reagent in 88 mM phosphate buffer, 11 mM KCl, 1 mM MgCl2, 55 mM 2ME, 4.4 mM chlorophenol red b-D-galactopyranoside (BMC 884-308). Incubation period varied from 30 minutes to 2 hours at 37° C. Results were read at 570 nm in an ELISA reader (Dynatech MR5000).
Concentrations Luciferase × Corrected
Preincubations [SEQ ID NO.:] micromolar 106 Beta-gal values luc/bgal
KLGFFKR [SEQ ID NO:7] 10 13 0.395 32.91
KLGFFKR [SEQ ID NO:7] 50 20 0.443 45.15
KLGFFKR [SEQ ID NO:7] 100 28 0.452 61.95
KLRFGFK [SEQ ID NO:29] 10 14 0.333 42.04
KLRFGFK [SEQ ID NO:29] 50 16 0.387 41.34
KLRFGFK [SEQ ID NO:29] 100 14 0.434 32.26
no retinoic acid 0 0.17 0.348 0.49
10−7 retinoic 0 8.3 0.323 25.7
Proposed Exploring Hydrophobic
Peptides [SEQ ID NO.:] Variants Protection Patch
RKFFGK [SEQ ID NO.: 32] Reversed X
d(KGFFKR) D-amino X
FGKKRK [SEQ ID NO.: 33] another X
Ac- [SEQ ID NO.: 34] Acetylated X
KGFFKR peptide
KGLFKR [SEQ ID NO.: 35] X
KGFLKR [SEQ ID NO.: 36] X
KGYFKR [SEQ ID NO.: 37] X
KGFYKR [SEQ ID NO.: 38] X
KGPFKR [SEQ ID NO.: 39] X
KGFPKR [SEQ ID NO.: 40] X
KFGFKR [SEQ ID NO.: 41] Inversion X
KGDFKR [SEQ ID NO.: 42] X
KGFKDR [SEQ ID NO.: 43] X
[SEQ ID NO.:] RAR/RXR AR
KLGFFKR [SEQ ID NO.: 7] 100%  62%
KGFFKR [SEQ ID NO: 5] 100%  N.D.
KVFFKR [SEQ ID NO: 3] N.D. 100%
KLRFGFK [SEQ ID NO.: 29] 34% n.d.
GLGFFKR [SEQ ID NO.: 44] 45% 100%
KLDFFKR [SEQ ID NO.: 45] 73%* 0%*
KLGRFKR [SEQ ID NO.: 46] 24% 10%
KLGFRKR [SEQ ID NO.: 47] 20% 6%
KLGFFGR [SEQ ID NO.: 48] 65% 85%*
KLGFFKG [SEQ ID NO.: 49] 22%* 63%*
*significant selectivity of these peptides for one receptor over the other.
The most critical amino acids appear to be F, F, and R in the sequence KLGFFKR [SEQ ID NO:7]. These three amino acids are completely invariant in all steroid and nuclear hormone receptors as well as in integrins.
Patient Normal Atrophy BPH PIN CA
1 1+ +/− 2+ 4+ 3-4+
2 1-2+ N/A 3+ 3-4+ 3-4+
3 1-2+ +/1 2+ 4+ 3-4+
4 2+ 1+ 2+ 4+ 2-3+
5 1-2+ 1+ 1-2+ 3-4+ 3-4+
6 1+ 1+ N/A 3+ 2-3+
7 1-2+ 1+ 1-2+ 3-4+ 5-4+
8 1-2+ 1+ 1-2+ 4+ 3-4+
9 +/− 0 N/A 2+ 1-2+
10 2+ 2+ N/A 2+ 2-4+
PIN: Prostatic intrapithelial neoplasia
Parallel paraffin sections from prostate biopsies were stained with Hemotoscylin and Eosin or by in situ hybridization with a calreticulin-specific antisense DNA probe. Calreticulin mRNA expression was confined to the epithelial tissue and dramatically increased, within the same section, from benign regions to PIN and CA regions. The extent of signal was evaluated independently by three pathologists. Some sections were also stained with the sense probe as control which was negative.
Number Sequence [SEQ ID NO:] shift)
285 KVFFKR [SEQ ID NO: 3] +
409 KGFFKR [SEQ ID NO: 5] +
410 KGFFRR (5 μG) [SEQ ID NO: 2] −/+
411 KAFFKR [SEQ ID NO: 4] +
412 GGFFKR [SEQ ID NO: 50] +/−
413 KDFFKR [SEQ ID NO: 51] −
414 KGRFKR [SEQ ID NO: 52] ++
415 KGFRKR [SEQ ID NO: 53] ++
416 KGFFGR [SEQ ID NO: 54] −
417 KGFFKG [SEQ ID NO: 55] −
418 GGFFRR [SEQ ID NO: 56] +
419 KDFFRR [SEQ ID NO: 57] −
420 KGRFRR [SEQ ID NO: 58] ++
421 KGFRRR [SEQ ID NO: 59] ++
422 KGFFRG [SEQ ID NO: 60] +/−
423 KGFFKK [SEQ ID NO: 61] −
424 KVFFKR (all D) +
425 KGFFKR (all D) +
426 AVFFKR [SEQ ID NO: 62] +/−
427 KVAFKR [SEQ ID NO: 63] −
428 KVFFAR [SEQ ID NO: 64] +/−
429 KVFAKR [SEQ ID NO: 65] −
430 KVFFKA [SEQ ID NO: 66] −
431 KV(N- [SEQ ID NO: 63] ++
70 6 amino acids amino acid single linear peptide Peptide /note= “Amino acid 2 wherein Xaa is either Gly, Ala or Val.” Peptide /note= “Amino acid 5 wherein Xaa is either Lys or Arg.” 1 Lys Xaa Phe Phe Xaa Arg 1 5 6 amino acids amino acid single linear peptide 2 Lys Gly Phe Phe Arg Arg 1 5 6 amino acids amino acid single linear peptide 3 Lys Val Phe Phe Lys Arg 1 5 6 amino acids amino acid single linear peptide 4 Lys Ala Phe Phe Lys Arg 1 5 6 amino acids amino acid single linear peptide 5 Lys Gly Phe Phe Lys Arg 1 5 6 amino acids amino acid single linear peptide 6 Thr Gly Phe Phe Lys Arg 1 5 7 amino acids amino acid single linear peptide 7 Lys Leu Gly Phe Phe Lys Arg 1 5 71 amino acids amino acid single linear peptide 8 Lys Pro Cys Phe Val Cys Gln Asp Lys Ser Ser Cys Tyr His Tyr Cys 1 5 10 15 Val Ser Ala Cys Glu Gly Cys Lys Gly Phe Phe Arg Arg Ser Ile Gln 20 25 30 Lys Asn Met Val Tyr Thr Cys His Arg Asp Lys Asn Cys Gln Asp Lys 35 40 45 Ser Ser Cys Tyr His Tyr Cys Val Ser Ala Cys Arg Leu Gln Lys Cys 50 55 60 Phe Glu Val Gly Met Ser Lys 65 70 6 amino acids amino acid single linear peptide 9 Xaa Gly Phe Phe Lys Arg 1 5 7 amino acids amino acid single linear peptide 10 Lys Xaa Gly Phe Phe Xaa Arg 1 5 7 amino acids amino acid single linear peptide 11 Lys Ile Gly Phe Phe Lys Arg 1 5 7 amino acids amino acid single linear peptide 12 Lys Cys Gly Phe Phe Lys Arg 1 5 7 amino acids amino acid single linear peptide 13 Lys Ala Gly Phe Phe Lys Arg 1 5 7 amino acids amino acid single linear peptide 14 Lys Cys Gly Phe Phe Asp Arg 1 5 7 amino acids amino acid single linear peptide 15 Arg Met Gly Phe Phe Lys Arg 1 5 7 amino acids amino acid single linear peptide 16 Lys Val Gly Phe Phe Lys Arg 1 5 7 amino acids amino acid single linear peptide 17 Lys Cys Gly Phe Phe Asn Arg 1 5 15 amino acids amino acid single linear peptide 18 Ala Cys Glu Gly Cys Lys Gly Phe Phe Arg Arg Ser Ile Gln Lys 1 5 10 15 15 amino acids amino acid single linear peptide 19 Thr Cys Glu Gly Cys Lys Gly Phe Phe Arg Arg Thr Ile Gln Lys 1 5 10 15 15 amino acids amino acid single linear peptide 20 Thr Cys Glu Gly Cys Lys Gly Phe Phe Arg Arg Ser Met Lys Arg 1 5 10 15 15 amino acids amino acid single linear peptide 21 Thr Cys Gly Ser Cys Lys Val Phe Phe Lys Arg Ala Val Glu Gly 1 5 10 15 15 amino acids amino acid single linear peptide 22 Thr Cys Gly Ser Cys Lys Val Phe Phe Lys Arg Ala Ala Ala Gly 1 5 10 15 15 amino acids amino acid single linear peptide 23 Thr Cys Gly Ser Cys Lys Val Phe Phe Lys Arg Ala Met Glu Gly 1 5 10 15 15 amino acids amino acid single linear peptide 24 Ser Cys Glu Gly Cys Lys Ala Phe Phe Lys Arg Ser Ile Gln Gly 1 5 10 15 15 amino acids amino acid single linear peptide 25 Ser Cys Glu Gly Cys Lys Gly Phe Phe Lys Arg Thr Val Arg Lys 1 5 10 15 15 amino acids amino acid single linear peptide 26 Thr Cys Glu Gly Cys Thr Gly Phe Phe Lys Arg Ser Ile Arg Lys 1 5 10 15 15 amino acids amino acid single linear peptide 27 Thr Cys Glu Gly Cys Lys Gly Phe Phe Lys Arg Thr Val Gln Lys 1 5 10 15 26 base pairs nucleic acid double linear DNA (genomic) 28 GTAAAGTACT CCAAGAACCT ATTTGT 26 7 amino acids amino acid single linear peptide 29 Lys Leu Arg Phe Gly Phe Lys 1 5 7 amino acids amino acid single linear peptide 30 Lys Xaa Gly Phe Phe Lys Arg 1 5 7 amino acids amino acid single linear peptide 31 Lys Leu Xaa Phe Phe Lys Arg 1 5 6 amino acids amino acid single linear peptide 32 Arg Lys Phe Phe Gly Lys 1 5 6 amino acids amino acid single linear peptide 33 Phe Gly Lys Lys Arg Lys 1 5 6 amino acids amino acid single linear peptide Peptide /note= “Amino acid 1 wherein Lys is acetylated.” 34 Lys Gly Phe Phe Lys Arg 1 5 6 amino acids amino acid single linear peptide 35 Lys Gly Leu Phe Lys Arg 1 5 6 amino acids amino acid single linear peptide 36 Lys Gly Phe Leu Lys Arg 1 5 6 amino acids amino acid single linear peptide 37 Lys Gly Tyr Phe Lys Arg 1 5 6 amino acids amino acid single linear peptide 38 Lys Gly Phe Tyr Lys Arg 1 5 6 amino acids amino acid single linear peptide 39 Lys Gly Pro Phe Lys Arg 1 5 6 amino acids amino acid single linear peptide 40 Lys Gly Phe Pro Lys Arg 1 5 6 amino acids amino acid single linear peptide 41 Lys Phe Gly Phe Lys Arg 1 5 6 amino acids amino acid single linear peptide 42 Lys Gly Asp Phe Lys Arg 1 5 6 amino acids amino acid single linear peptide 43 Lys Gly Phe Lys Asp Arg 1 5 7 amino acids amino acid single linear peptide 44 Gly Leu Gly Phe Phe Lys Arg 1 5 7 amino acids amino acid single linear peptide 45 Lys Leu Asp Phe Phe Lys Arg 1 5 7 amino acids amino acid single linear peptide 46 Lys Leu Gly Arg Phe Lys Arg 1 5 7 amino acids amino acid single linear peptide 47 Lys Leu Gly Phe Arg Lys Arg 1 5 7 amino acids amino acid single linear peptide 48 Lys Leu Gly Phe Phe Gly Arg 1 5 7 amino acids amino acid single linear peptide 49 Lys Leu Gly Phe Phe Lys Gly 1 5 6 amino acids amino acid single linear peptide 50 Gly Gly Phe Phe Lys Arg 1 5 6 amino acids amino acid single linear peptide 51 Lys Asp Phe Phe Lys Arg 1 5 6 amino acids amino acid single linear peptide 52 Lys Gly Arg Phe Lys Arg 1 5 6 amino acids amino acid single linear peptide 53 Lys Gly Phe Arg Lys Arg 1 5 6 amino acids amino acid single linear peptide 54 Lys Gly Phe Phe Gly Arg 1 5 6 amino acids amino acid single linear peptide 55 Lys Gly Phe Phe Lys Gly 1 5 6 amino acids amino acid single linear peptide 56 Gly Gly Phe Phe Arg Arg 1 5 6 amino acids amino acid single linear peptide 57 Lys Asp Phe Phe Arg Arg 1 5 6 amino acids amino acid single linear peptide 58 Lys Gly Arg Phe Arg Arg 1 5 6 amino acids amino acid single linear peptide 59 Lys Gly Phe Arg Arg Arg 1 5 6 amino acids amino acid single linear peptide 60 Lys Gly Phe Phe Arg Gly 1 5 6 amino acids amino acid single linear peptide 61 Lys Gly Phe Phe Lys Lys 1 5 6 amino acids amino acid single linear peptide 62 Ala Val Phe Phe Lys Arg 1 5 6 amino acids amino acid single linear peptide Peptide /note= “Amino acid 3 wherein Ala may be acetylated.” 63 Lys Val Ala Phe Lys Arg 1 5 6 amino acids amino acid single linear peptide 64 Lys Val Phe Phe Ala Arg 1 5 6 amino acids amino acid single linear peptide 65 Lys Val Phe Ala Lys Arg 1 5 6 amino acids amino acid single linear peptide 66 Lys Val Phe Phe Lys Ala 1 5 6 amino acids amino acid single linear peptide Peptide 3, 4, 5 /note= “Xaa is a basic amino acid” 67 Lys Gly Xaa Xaa Xaa Arg 1 5 6 amino acids amino acid single linear peptide Peptide /note= “Amino acid 2 wherein Xaa is either Gly, Ala or Val.” 68 Lys Xaa Phe Phe Lys Arg 1 5 6 amino acids amino acid single linear peptide Peptide /note= “Amino acid 2 wherein Xaa is either Gly, Ala or Val.” 69 Lys Xaa Phe Phe Arg Arg 1 5 15 amino acids amino acid single linear peptide Peptide /note= “Amino acid 1 is acetylated.” 70 Ser Cys Glu Gly Cys Lys Ala Phe Phe Lys Arg Ser Ile Gln Gly 1 5 10 15
US5389517 Jun 18, 1993 Feb 14, 1995 Trustees Of Boston University Specific antibodies against the DNA-binding domain of and immunoassays to determine the presence and functional status of estrogen receptor proteins
US5426097 Apr 6, 1993 Jun 20, 1995 The Trustees Of Columbia University In The City Of New York Calreticulin: a novel antithrombotic agent
CA2140814A1 Jan 23, 1995 Jul 24, 1996 Shoukat Dedhar Use of calreticulin in modulating hormone responsiveness and new pharmaceuticals for treating cancer, osteoporosis and chronic inflammatory disease
WO1993014098A1 Jan 11, 1993 Jul 22, 1993 Sloan-Kettering Institute For Cancer Research Antigen recognized by patients with antibody associated lambert-eaton myasthenic syndrome (lems), dna encoding same and uses thereof
WO1996023001A1 Nov 23, 1995 Aug 1, 1996 Shoukat Dedhar New pharmaceuticals for modulating hormone responsiveness
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19 Fliegel et al., "Molecular Cloning of the High Affinity Calcium-binding Protein (Calreticulin) of Skeletal Muscle Sarcoplasmic Reticulum", The Journal of Biological Chemistry, vol. 264, No. 36, pp. 21522-21528 (Dec. 25, 1989).
20 Giguère et al., "Molecular Cloning of cDNA Encoding a Second Cellular Retinoic Acid-binding Protein", Proc. Natl. Acad. Sci. USA, vol. 87, pp. 6233-6237 (Aug. 1990).
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26 Lee et al., "The Expression and Posstranslational Modification of a Neuron-Specific beta-Tubulin Isotype During Chick Embryogenesis", Cell Motility and the Cytoskeleton, vol. 17, pp. 118-132 (1990).
27 Lee et al., "The Expression and Posstranslational Modification of a Neuron-Specific β-Tubulin Isotype During Chick Embryogenesis", Cell Motility and the Cytoskeleton, vol. 17, pp. 118-132 (1990).
28 Leung-Hagesteijn et al., "Cell Attachment to Extracellular Matrix Substrates is Inhibited Upon Downregulation of Expression of Calreticulin, an Intracellular Integrin alpha-subunit-binding Protein", Journal of Cell Science, vol. 107, pp. 589-600 (1994).
29 Leung-Hagesteijn et al., "Cell Attachment to Extracellular Matrix Substrates is Inhibited Upon Downregulation of Expression of Calreticulin, an Intracellular Integrin α-subunit-binding Protein", Journal of Cell Science, vol. 107, pp. 589-600 (1994).
30 Luisi et al., "Crystallographic Analysis of the Interaction of the Glucocorticoid Receptor with DNA", Nature, vol. 352, pp. 497-505 (Aug. 8, 1991).
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34 McCauliffe et al., "A Human Ro/SS-A Autoantigen is the Homologue of Calreticulin and is Highly Homologous with Onchocercal RAL-1 Antigen and an Aplysia ‘Memory Molecule’", J. Clin. Invest., vol. 86, pp. 332-335 (Jul. 1990).
35 Michalak et al., "Calreticulin", Biochemistry Journal, vol. 285, pp. 681-692 (1992).
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37 Morrison et al., "Prediction of Bone Density from Vitamin D Receptor Alleles", Nature, vol. 367, pp. 284-287 (Jan. 20, 1994).
38 Murthy et al., "Structural homology between the rat calreticulin gene product and the Onchocerca volvulus antigen Ral-1" Nucleic Acids Research 18(16) 4933.
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49 Shoukat Dedhar, "Novel Functions for Calreticulin: Interaction with Integrins and Modulation of Gene Expression", Trends in Biochemical Sciences, vol. 19, No. 7, pp. 269-271 (Jul. 1994).
50 * Stryer, Biochemistry, W.H. Freeman and Company, San Francisco, pp. 13-16, 1981.*
51 Sucov et al., "Characterization of an Autoregulated Response Element in the Mouse Retinoic Acid Receptor Type beta Gene", Proc. Natl. Acad. Sci. USA, vol. 87, pp. 5392-5396 (Jul. 1990).
52 Sucov et al., "Characterization of an Autoregulated Response Element in the Mouse Retinoic Acid Receptor Type β Gene", Proc. Natl. Acad. Sci. USA, vol. 87, pp. 5392-5396 (Jul. 1990).
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55 Tilley et al., "Detection of Discrete Androgen Receptor Epitopes in Prostate Cancer by Immunostaining: Measurement by Color Video Image Analysis", Cancer Research, vol. 54, pp. 4096-4102 (Aug. 1, 1994).
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US8158586 * Apr 11, 2006 Apr 17, 2012 Pharmagap Inc. Inhibitors of protein kinases and uses thereof
WO2012088309A1 * Dec 21, 2011 Jun 28, 2012 The Board Of Trustees Of The Leland Stanford Junior University Therapeutic and diagnostic methods for manipulating phagocytosis through calreticulin and low density lipoprotein-related receptor
U.S. Classification 530/300, 530/329, 530/327, 530/328, 530/325, 530/324, 530/326
International Classification A61P19/10, A61K9/127, C07K7/06, C07K14/47, A61K38/00, A61P19/02, A61P35/00, C07K7/08
Cooperative Classification C07K14/4725, C07K7/08, C07K7/06
European Classification C07K7/08, C07K7/06, C07K14/47A15

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2. OVERALL VIEW OF BRIDGE AND LITTLE COLORADO RIVER. VIEW TO WEST. - Holbrook Bridge, Spanning Little Colorado River at AZ 77, Holbrook, Navajo County, AZ skip navigation
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Title: 2. OVERALL VIEW OF BRIDGE AND LITTLE COLORADO RIVER. VIEW TO WEST. - Holbrook Bridge, Spanning Little Colorado River at AZ 77, Holbrook, Navajo County, AZ
Reproduction Number: HAER ARIZ,9-HOLB.V,1--2
Call Number: HAER ARIZ,9-HOLB.V,1--2
http://www.loc.gov/pictures/item/az0228.photos.009786p/
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Build my business website for my brand
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Testing i18n in Django for the Molly Project : djangojump to contentmy subredditsannouncementsArtAskRedditaskscienceawwblogbookscreepydataisbeautifulDIYDocumentariesEarthPornexplainlikeimfivefoodfunnyFuturologygadgetsgamingGetMotivatedgifshistoryIAmAInternetIsBeautifulJokesLifeProTipslistentothismildlyinterestingmoviesMusicnewsnosleepnottheonionOldSchoolCoolpersonalfinancephilosophyphotoshopbattlespicsscienceShowerthoughtsspacesportstelevisiontifutodayilearnedTwoXChromosomesUpliftingNewsvideosworldnewsWritingPromptsedit subscriptionsfront-all-random | AskReddit-funny-pics-videos-todayilearned-gaming-worldnews-gifs-aww-news-Showerthoughts-movies-mildlyinteresting-IAmA-Jokes-photoshopbattles-tifu-nottheonion-television-sports-TwoXChromosomes-science-OldSchoolCool-explainlikeimfive-UpliftingNews-food-personalfinance-space-creepy-Futurology-WritingPrompts-LifeProTips-Music-EarthPorn-DIY-books-GetMotivated-nosleep-Art-askscience-history-dataisbeautiful-Documentaries-gadgets-listentothis-philosophy-InternetIsBeautiful-announcements-blogmore » djangocommentsWant to join? Log in or sign up in seconds.|Englishlimit my search to /r/djangouse the following search parameters to narrow your results:subreddit:subredditfind submissions in "subreddit"author:usernamefind submissions by "username"site:example.comfind submissions from "example.com"url:textsearch for "text" in urlselftext:textsearch for "text" in self post contentsself:yes (or self:no)include (or exclude) self postsnsfw:yes (or nsfw:no)include (or exclude) results marked as NSFWe.g. subreddit:aww site:imgur.com dogsee the search faq for details.advanced search: by author, subreddit...this post was submitted on 04 Jun 20113 points (67% upvoted)shortlink: remember mereset passwordloginSubmit a new linkSubmit a new text postdjangosubscribeunsubscribe16,873 readers~17 users here nowNews and links for Django developers.
a community for 8 yearsmessage the moderatorsMODERATORSsimonwkingkilrkennethloveubernostrumabout moderation team »discussions in /r/django<>XAnalytics for django rest?5 points · 9 comments How to write a python script to massage db data?0 points · 12 comments New to Python (and coding in general) and I want to be able to build a Django website as soon as possible. Any videos, free classes or readings you can recommend?9 points · 11 comments Two versions of Python on same system0 points · 2 comments How can I pass the current language to a spawned thread?0 points · 5 comments Is it possible to use Django's admin panel without the rest of Django?1 points · 21 comments When should I redirect and when should I raise a 404?0 points · 8 comments Troubles with MySQL in venv30 points · 24 comments What's your stack?6 points · 2 comments Multi tenantThis is an archived post. You won't be able to vote or comment.
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text:
The Odyssey by Homer | 2940012640765 | NOOK Book (eBook) | Barnes & Noble
Overview The poem mainly centers on the Greek hero Odysseus and his long journey home following the fall of Troy. It takes Odysseus ten years to reach Ithaca after the ten-year Trojan War. In his absence, it is assumed he has died, and his wife Penelope and son Telemachus must deal with a group of unruly suitors, the Mnesteres or Proci, competing for Penelope's hand in marriage. Read More Show Less ...
The poem mainly centers on the Greek hero Odysseus and his long journey home following the fall of Troy. It takes Odysseus ten years to reach Ithaca after the ten-year Trojan War. In his absence, it is assumed he has died, and his wife Penelope and son Telemachus must deal with a group of unruly suitors, the Mnesteres or Proci, competing for Penelope's hand in marriage.
BN ID: 2940012640765


text:
GeoSafari Mini Ant Factory! | eBay
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NIP VINTAGE "ANT FAMILY" MINI ANT FARM by Mountains plastic factory
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Verified purchase: Yes | Condition: new | Sold by: tnmtndk
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Cool learning toy
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text:
Amazon.com: ZOMBIES: Odessey & Oracle: Music
Vinyl, Limited Edition, Import, May 15, 2007
Vinyl $60.64
Odessey & Oracle [Extra tracks,Import]
This item: Odessey & Oracle ~ The Zombies Audio CD $17.06
Begin Here ~ The Zombies Audio CD $23.46
Zombies ~ The Zombies Audio CD $11.99
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Audio CD$12.35 Prime Begin Here
Audio CD$23.46 Prime Odessey and Oracle [Vinyl]
Vinyl$22.99 Prime Breathe Out Breathe in
Audio CD$14.99 Prime The Singles Collection: A's & B's, 1964-1969
German digipak reissue of the British Invasion act's 1968 album with 16 bonus tracks, 'I'll Call You Mine', 'She Loves the Way They Love Her', 'Imagine the Swan', 'Smokey Day', 'I'f it Don't Work Out', 'I Know She Will', 'Don't Cry For Me', 'Walking in the Sun', 'Conversation Off Floral Street', 'I Want You Back Again', 'Gotta Get a Hold of Myself', 'GoinOut of My Head', 'She Does Everything For Me', 'Nothing's Changed', 'I Could Spend the Day' and 'Girl Help Me'. Digipack. 2001 release.
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(Redirected from Gated D latch)
From the teaching point of view, SR latches realised as a pair of cross-coupled components (transistors, gates, tubes, etc.) are rather hard to understand for beginners. A didactically easier to understand model uses a feedback loop instead of the cross-coupling. The following is an SR latch built with an AND gate with one inverted input and an OR gate.
^ Langholz, Gideon; Kandel, Abraham; Mott, Joe L. (1998). Foundations of Digital Logic Design. Singapore: World Scientific Publishing Co. Ptc. Ltd. p. 344. ISBN 978-981-02-3110-1. ^ Hinrichsen, Diederich; Pritchard, Anthony J. (2006). Mathematical Systems Theory I: Modelling, State Space Analysis, Stability and Robustness. Springer. pp. 63–64. ISBN 9783540264101. ^ Farhat, Hassan A. (2004). Digital design and computer organization. 1. CRC Press. p. 274. ISBN 978-0-8493-1191-8. ^ a b Kogge, Peter M. (1981). The Architecture of Pipelined Computers. McGraw-Hill. pp. 25–27. ISBN 0-07-035237-2. ^ Cotten, L. W. (1965). "Circuit Implementation of High-Speed Pipeline Systems". AFIPS Proc. Fall Joint Computer Conference: 489–504. doi:10.1145/1463891.1463945. ^ Earle, J. (March 1965). "Latched Carry-Save Adder". IBM Technical Disclosure Bulletin. 7 (10): 909–910. ^ a b Omondi, Amos R. (1999-04-30). The Microarchitecture of Pipelined and Superscalar Computers. Springer. pp. 40–42. ISBN 978-0-7923-8463-2. ^ a b Kunkel, Steven R.; Smith, James E. (May 1986). "Optimal Pipelining in Supercomputers". ACM SIGARCH Computer Architecture News. ACM. 14 (2): 404–411 [406]. CiteSeerX 10.1.1.99.2773 . doi:10.1145/17356.17403. ISSN 0163-5964. ^ The D Flip-Flop
^ a b Mano, M. Morris; Kime, Charles R. (2004). Logic and Computer Design Fundamentals, 3rd Edition. Upper Saddle River, NJ, USA: Pearson Education International. pp. pg283. ISBN 0-13-191165-1. ^ a b Harris, S; Harris, D (2016). Digital Design and Computer Architecture - ARM Edition,. Morgan Kaufmann, Waltham, MA. ISBN 978-0-12-800056-4. ^ Chaney, Thomas J.; Molnar, Charles E. (April 1973). "Anomalous Behavior of Synchronizer and Arbiter Circuits". IEEE Transactions on Computers. C–22 (4): 421–422. doi:10.1109/T-C.1973.223730. ISSN 0018-9340. ^ Often attributed to Don Knuth (1969) (see Midhat J. Gazalé (2000). Number: from Ahmes to Cantor. Princeton University Press. p. 57. ISBN 978-0-691-00515-7. ), the term flip-flap-flop actually appeared much earlier in the computing literature, for example, Bowdon, Edward K. (1960). The design and application of a "flip-flap-flop" using tunnel diodes (Master's thesis). University of North Dakota. , and in Alexander, W. (Feb 1964). "The ternary computer". Electronics and Power. IET. 10 (2): 36–39. doi:10.1049/ep.1964.0037. ^ "Ternary "flip-flap-flop"". ^ US 6975152 ^ Irving, Thurman A.; Shiva, Sajjan G.; Nagle, H. Troy (March 1976). "Flip-Flops for Multiple-Valued Logic". Computers, IEEE Transactions on. C–25 (3): 237–246. doi:10.1109/TC.1976.5009250. ^ Wu, Haomin; Zhuang Nan (1991). "Research into ternary edge-triggered JKL flip-flop". Journal of Electronics (China). 8 (Volume 8, Number 3 / July, 1991): 268–275. doi:10.1007/BF02778378. External links[edit]
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Why Two Phone Companies Are Better Than One - Bloomberg
Why Two Phone Companies Are Better Than One
As the tens of thousands of air travelers marooned in New York area airports on Sept. 17 can attest, when a vital telephone network goes on the fritz, everything can come to a screeching halt. Shortly before 5 p.m. on that fateful day, an American Telephone & Telegraph Co. switch in lower Manhattan lost power, severing a vital link in the Federal Aviation Ad-ministration's network. With air traffic controllers cut off from one another, nothing moved in or out of the three major airports for hours. Imagine if the same thing happened to your business.
The good news, according to telecommunications experts, is that such a complete telecommunications breakdown can be avoided. Even though most network problems are beyond the control of a company's telecommunications department, good backup systems--the kind the FAA lacked--can prevent a total collapse. "What happened to the FAA shouldn't happen to everyone," says James Bailie, a consultant with Independent Telecommunications Services in Bethesda, Md.
The answer? In a word, diversity. Michael Finneran, a telecommunications consultant with dBRN Associates Inc. in Hewlett Park, N. Y., says companies should have at least two long-distance providers. If your primary carrier is AT&T, get accounts with MCI Communications Corp., U. S. Sprint Communications Co., or another long-distance company. In a pinch, for every outgoing call, you can dial the access codes consumers use to select carriers when dialing from pay phones: 10288 for AT&T, 10222 for MCI, and 10333 for Sprint.
CROSSED WIRES. Many big companies routinely use multiple carriers, and not just for backups. Bear, Stearns & Co., the New York brokerage, divides its huge phone traffic among several carriers. It's like having multiple oil pipelines, each filled to half capacity, explains Jeff Marshall, managing director of Bear Stearns's communications department. The setup can handle any increase in phone traffic as well as take up any slack from a failed carrier. But one catch, warns consultant Bailie: Dividing long-distance calls among many different carriers can raise costs by preventing companies from getting the maximum volume-calling discounts.
Even with multiple long-distance services, phone customers could still be vulnerable to some breakdowns. Although most customers would never know it, phone companies often lease circuits from one another. So even if you have a second carrier, it might actually be using the same lines as your primary carrier. Thus, a single accidental cut of a wire or fiber-optic cable can wipe out both carriers. Consultants advise that phone customers make sure they are not just buying what's known in the trade as "diagram diversity"--the appearance of alternate routing. To be sure that your calls will travel over multiple, independent paths, make your carriers spell out exactly how your calls will be routed.
While a simple backup system could have easily saved the FAA from the Sept. 17 fiasco, the agency did not have the freedom that businesses have when arranging phone service. Like other agencies, the FAA orders its phone service under strict federal procurement rules. Realizing it was vulnerable, the FAA had been lobbying the General Services Administration for permission to solicit bids to get a more secure system. The GSA had resisted, ruling that the FAA should buy its phone service under the terms of FTS-2000, the huge phone contract that serves other government agencies. In light of the recent troubles, however, the FAA is negotiating a compromise with the GSA.
SHARING THE LOAD. Finding a backup to protect your business from a failure in the local phone system is a bit trickier. Almost everywhere in the U. S., there is only one local phone company. Large customers can protect themselves bybypassing the local phone network to link directly to long-distance carriers, via microwave antennas or fiber-optic cables. Chrysler Corp., for instance, communicates with dealers via a network of satellite dishes. For those who don't want to build such networks themselves, businesses have sprung up in major cities that offer shared fiber-optic networks connecting subscribers to their long-distance carriers. "Don't put all your eggs in one basket" is the advertising slogan of one such network, New York-based Teleport Communications Group.
One of the biggest hurdles in diversification is how to deal with 800 numbers and other special lines. For now at least, each carrier can supply companies with a toll-free number that works only within its network. They can't be switched to another carrier. So, should a long-distance network fail, the toll-free number can't be replaced--except with a new 800 number.
Frost & Sullivan Inc., a market researcher, recently projected that U. S. companies will sharply increase spending to keep their telecommunications networks running. The company predicts that revenues in the network security market will jump from $8.2 billion in 1990 to about $18 billion in 1996. With nightmares such as the FAA mess serving as object lessons, businesses don't have to be convinced that it's worth spending some extra money to protect their vital phone links.
HOW TO PROTECT YOUR TELEPHONE NETWORK
1. Don't rely on just one service. Split traffic between long-distance carriers such as MCI or AT&T
2. Insist that competing long-distance carriers don't route your calls over the same physical line or path. Carriers often sell capacity to one another, so it pays to check
3. Look for alternate routes to your long-distance carriers so your phones won't be crippled if the local phone company has a glitch. In some cities, you can bypass the local phone company by using another carrier to connect to long-distance services. Microwave and satellite links are also options

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