text:
|Project Name
|Price (USD)
|Project Name
|Price (USD)
|Single template page for Wordpress
|I would like a wordpress template file to output news with 5 per row, 7 rows total. Image URL will be...pixels) followed by the title underneath. CSS, I would like the rounded corners if possible in
|PHP, XML, Project Management, Engineering, CSS, Software Architecture, Software Testing, Website Testing, MySQL, Website Management, Web Hosting
|Feb 26, 2010
|Feb 26, 2010Ended
|Single Page Wordpress website
|...into a fully functional Wordpress website. There's some funky scrolling and CSS I'd like you to do, but
|PHP, Website Design, CSS, HTML
|May 1, 2013
|May 1, 2013Ended
|Single page wordpress theme
|...PSD to a wordpress theme. the theme is SINGLE PAGE WEBSITE with homepage, blog page and post page only. ... - HTML / CSS / Jquery needs to be ready within 3 days. - wordpress will need to be completed within...PLEASE BID ONLY IF: - YOU HAVE EXPERIENCE IN SINGLE PAGE WEBSITES WITH JQUERY CODE - YOU CAN FINISH
|PHP, Wordpress, CSS, HTML, jQuery / Prototype
|Jun 2, 2013
|Jun 2, 2013Ended
|Single page modification in wordpress (html and CSS)
|Hello, I have a single wordpress page to complete the design per the attached drafts http://guyazouri...http://guyazouri.co.uk/clondon/?page_id=52 The page need this page to look EXACTLY like the draft, pixel by pixel...uk/clondon/?page_id=144 Please be aware this is a single page with tabs and different content.
|PHP, Wordpress, CSS, PSD to HTML
|May 24, 2013
|May 24, 2013Ended
|Single Web Page Developed
|I need a single web page developed to look in a similar style to this example website: http://www.slidedeck...Should be developed in PHP, CSS and HTML and integrate with an existing Wordpress website (cannot be ripped...Deliverables to guarantee payment are: 1 PHP file, 1 CSS file, image files (for borders, backgrounds, etc
|PHP, Website Design, Wordpress, CSS, HTML
|Aug 12, 2012
|Aug 12, 2012Ended
|single HTML5 page with CSS
|...simple "comming soon" page. We already have a graphic in .eps format. The page will have a white background...towards the top of the page. Text will include "Comming Soon" in the center of the page. Contact information...information needs to be centered towards the bottom of the page.
|Website Design, Graphic Design, CSS, HTML
|Aug 16, 2012
|Aug 16, 2012Ended
|Single Home Page with CSS
|We need a single homepage built by following the attached sample. CSS should not be inline, but
|PHP, Engineering, CSS, Software Architecture, Software Testing, MySQL
|Feb 8, 2006
|Feb 8, 2006Ended
|Design Single Page with CSS
|...It's a very simple page with image and a mini subscribe now form. I need it in CSS The catch is this
|Engineering, Software Architecture, Software Testing, Visual Arts
|Dec 15, 2011
|Dec 15, 2011Ended
|create CSS for single page
|Deliver a nice looking CSS for the http://www.tm-rating.org/ home page. Warning: this site only shows
|PHP, Logo Design, Engineering, User Interface / IA, Software Architecture, Arts & Crafts, Software Testing, Website Testing, MySQL, Website Management, Web Hosting
|Jun 25, 2007
|Jun 25, 2007Ended
|Single php/css page
|...simple landing page. From this image I need to create a php page with the associated css file: You...the image (the way I want the page to look) - Produce from this a Css and a php file with the components...able to edit the text and replace the images in the page as per my convenience. You will deliver this within
|PHP, Javascript, CSS
|Aug 3, 2012
|Aug 3, 2012Ended
|Single page CSS and HTML
|...someone with fast skills to make the CSS and HTML for a SINGLE PAGE. I need someone who can make it today
|CSS, Firefox, Google Chrome, Apple Safari
|Apr 6, 2013
|Apr 6, 2013Ended
|Single page in css
|A simple page to be coded in css, should render in all browsers. One link on page. Very simple job, need
|PHP, Project Management, Engineering, CSS, Software Architecture, Software Testing, Website Testing, MySQL, Website Management, Web Hosting
|Jan 4, 2010
|Jan 4, 2010Ended
|css design single page
|hi sandy, i want to single page css page Search section above and logos, only at the bottom listing What
|Aug 19, 2014
|Aug 19, 2014Ended
|Single page landing page to be coded
|I have designed a website and its a single page landing page which needs some JS work. The calculator...form. If you can do wordpress it will be a plus point if not we can do html css too. I need this fast
|PHP, Website Design, Graphic Design, HTML
|Jun 12, 2013
|Jun 12, 2013Ended
|.PSD to CSS, single page
|...need a photoshop webpage design to be converted to css. The html elements are already completed
|Website Design, PSD to HTML, HTML
|Sep 9, 2010
|Sep 9, 2010Ended
|SIngle Page CSS Website
|...development. **We need a Logo and a single page Classy ... CSS Website. ** One rough sketch attached...web 2.0 standards 1. And W3C CSS and W3C XHTML compliant 2. ALL CSS … no tables and TR TD 3. Round...coder's Seller Legal Agreement). ## Platform CSS, HTML/XHTML, Internet Explorer FireFox Chrome
|PHP, XML, Logo Design, Engineering, CSS, Software Architecture, Software Testing, MySQL, Visual Arts
|Mar 20, 2010
|Mar 20, 2010Ended
|single page css design
|We have a single page PSD which we want to be converted into CSS. It needs to be xcss valid and browser...coder's Seller Legal Agreement). ## Platform css
|XML, CSS, Visual Arts
|Aug 20, 2009
|Aug 20, 2009Ended
|CSS-design for single page
|I need a design for only one single page. A preliminary design is given and looks like the attached image...does not need to be modified. The job is to deliver CSS and images (for rounded-edges etc.). I'm a professional
|CSS, Visual Arts
|Aug 21, 2009
|Aug 21, 2009Ended
|create news single page and css responsive change on a wordpress custom theme
|...be an expert in wordpress and quick to solve problems 1. create a seperate single page to display full...full news items, present page displays both exerpt news and full news in same page via jquery. 2. correct
|PHP, Wordpress, CSS, HTML5, LESS/Sass/SCSS
|Sep 9, 2015
|Sep 9, 2015Ended
|create single page and css responsive change on wordpress custom theme
|...be an expert in wordpress and quick to solve problems 1. create a seperate single page to display full...present page displays both exerpt news and full news in same page via jquery. 2. make responsive css styling
|PHP, Wordpress, CSS, HTML5, LESS/Sass/SCSS
|Sep 8, 2015
|Sep 8, 2015Ended


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We stayed here for a weekend family getaway in Dec 2012 and despite the kids disappointment that there was no pool, we found the hot tub, steam room and sauna a nice relaxing break from our room. Service was good and underground parking was nice. It's nicely located in the heart of downtown Banff and easy stroll to all the shops, restaurants and outdoor skating across the street. Thanks for a nice stay!
- Reservation Options:
- TripAdvisor is proud to partner with Expedia, Travelocity, Booking.com, TripOnline SA, Hotels.com, Odigeo, Priceline and Low Cost Holidays so you can book your Banff International Hotel reservations with confidence. We help millions of travelers each month to find the perfect hotel for both vacation and business trips, always with the best discounts and special offers.

subset: commoncrawl


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Parkview in Frisco Senior Apartments7450 Stonebrook Pkwy, Frisco, TX 75034
- Call for rates
- 1 Bed
Senior Living - Welcome to Parkview - an extraordinary community for independent seniors in the dynamic city of Frisco - where you'll experience a carefree lifestyle tailored to your needs! Enjoy beautiful apartment homes, all-inclusive amenities and services plus a vibrant social life! At Parkview, we make it a point to say yes - and make every day as comfortable and enjoyable as possible. We call it exceptional service. Youll call it home. Come settle in, make new friends and wonder why you didnt move in and join the Parkview family sooner!Healthy active seniors are looking for more convenience, fewer burdens, built-in social life and more freedom to do whatever it is they wish to do. Parkview in Frisco does just that - offering you peace of mind, luxury and independence without compromise. You have worked hard and planned for yourself, your children and your retirement. Now you can give up some of the more mundane tasks of your daily life and spend that time enjoying the things you always wished you had time for - supported by people who really care about you!Your beautiful apartment home is accented with granite countertops, plush carpet, ceramic tile, large walk-in shower or garden bath. Enjoy the view from your patio or balcony. What a great place to unwind after a fun day of activities with your neighbors! Make yourself at home! At Parkview, its all here, and all taken care of for you.The tight-knit residential feeling gives you all the privacy you need, yet all th
Parkview in Frisco is a senior apartment community located in Frisco, TX. View this 55+ apartment on a map.
Professionally Managed By: Parkview in Frisco
Community Features
- Activity Center
- Air Conditioning
- Business Center
- Controlled Access
- Covered Parking
- Fitness Center
- Garage
- Handicap Accessible
- High Speed Internet
- Maintenance
- Parking
- Pool
- Transportation
*Note: In Select Units


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3163 Views 1 Reply Latest reply: Sep 4, 2012 12:06 AM by bladerunner1712
bladerunner1712 Sep 4, 2012 12:06 AM
Re: Converting Mono to Stereo in response to Roger Villarreal Solved
Using a stereo mic rather than a mono one wouldn't make any difference when you're recording a single source of sound that doesn't move around. Do you really have a stereo capsule on a lavalier? ONce clip is in FCP all you need to do, assuming you don't want the audio in the centre of the stereo image, is pan the audio towards the left or right to suit using controls in the viewer audio tab.


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Quoizel Ceiling Lights & Chandeliers
Quoizel ceiling lights are specifically designed to complement your unique creations and enhance your home's quirks. Quoizel's collection of colorful chandeliers, pendants and flush mount lighting systems always ship to you for free with a complimentary bulb to instantly revitalize your room's atmosphere.
Quoizel - AMB5303VG - Ambrose Vintage Gold 16 Inch Chandelier$241.99
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text:
A blog by Jose Barreto, a member of the File Server team at Microsoft.
All messages posted to this blog are provided "AS IS" with no warranties, and confer no rights.
Information on unreleased products are subject to change without notice.
Dates related to unreleased products are estimates and are subject to change without notice.
The content of this site are personal opinions and might not represent the Microsoft Corporation view.
The information contained in this blog represents my view on the issues discussed as of the date of publication.
You should not consider older, out-of-date posts to reflect my current thoughts and opinions.
© Copyright 2004-2012 by Jose Barreto. All rights reserved.
Any sample code in this blog is covered under the "Microsoft Limited Public License", as described at the TechNet terms of use.
Follow @josebarreto on Twitter for updates on new blog posts.
Here are some notes on "SQL Server 2008 Database Checking" I took while attending an advanced class on SQL Server taught by Paul Randal (http://sqlskills.com/AboutPaulSRandal.asp).
Please note that, although these notes were taken during the class, I might have added some of my own (mis)interpretation :-). Always check your facts on Books Online (I try to provide links when applicable). As with anything else you get from a blog, never use any of this in production before you thoroughly validate it a test environment. Please keep in mind that some of those will be hard to follow without the right pre-requisite knowledge and the right context. Reading the post from top to bottom will help.
Checking databases
IO Errors
Page protection options
Automatic page repair
Evolution of CHECKDB
Running CHECKDB
CHECKDB checks
How frequently to run CHECKDB
How long does it take?
CHECKDB on VLDB
What to do?
Restore or Repair?
Lessons learned
Books Online: DBCC CHECKDBhttp://msdn.microsoft.com/en-us/library/ms176064.aspx
I took some advanced SQL Server 2008 classes recently and shared my notes in a series of blog posts.


text:
Watch Missing Season 1 Episode 4 online via TV Fanatic with over 2 options to watch the Missing S1E4 full episode. Affiliates with free and paid streaming include Amazon and iTunes.
Watch Similar
Shows FREE
|Watch Now
|Watch Now
Episode Details
Keith Carradine shows up again on this episode of Missing. His character reunites with Becca in order to track down the assassin who killed Paul.
- Show:
- Missing
- Season:
- Missing Season 1
- Episode Number:
- 4


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Resolution: standard / high
Figure 5.
Schematic view of tpm3 showing the advantage of integrating multiple databases in revealing alternative splicing pattern. (A) Schematic view of tpm3. dre03301_1 and dre03301_2 (in the red square) are remapped probe sets with probes from Dr.18559.1.S1_at and Dr.20297.1.S1_at (in the blue square) respectively. (B) Log-base 2 signals of the probes from the remapped probe sets with 3dpf and 5dpf gene expression in black and red dots, respectively. (C) The real-time PCR results depicted as relative quantification compared to lowest abundance sample.
Yin et al. BMC Genomics 2010 11:50 doi:10.1186/1471-2164-11-50


text:
A critical illness can drain your wealth, and this reflects on mortgage payments. UnbeatableLifeAndCriticalInsurance.co.uk of West Yorkshire is now offering critical illness cover with mortgage payment protection.
If you become unemployed because of a critical illness, the plan will cover your mortgage payments for a short while until you are able to work again or until you can find a job.


text:
Candidates must have 6 months of Warehouse or Order picking experience. Randstad has immediate openings for order pickers/warehouse workers in the East and...
Sep 25 - Knoxville, TN
Sep 22 - Knoxville, TN
As a picker you will be working in a state-of-the-art warehouse facility. Are you the type of worker who thrives on filling customer orders and making deadlines...
Sep 28 - Tennessee
Be able to perform all of the essential functions of craft workers under his/her supervision. Plan and communicate with the warehouse, purchasing, and...
Oct 1 - United States
Warehouse Order Picker – Part Time Seasonal. Ability and desire to work in a fast-paced warehouse environment....
Oct 9 - Knoxville, TN
Warehouse Worker $10.00 per Hr
Premier Manufacturing company seeking a Warehouse worker to start immediately. $10.00 per Hr.. Day shift. Start 6:00 AM till 4:30 PM. Call (423) 790-5254Apply today start Today!
Oct 9 -
Vonore - Construction & trades
Mall at Millenia, Lilly Pulitzer Store Florida Job Description Supports the Store Management team, in the achievement of the store's goals, by providing
Oct 5 - United States
Sales/Customer Service
Job Description Position Purpose: Sales associates provide fast, friendly service by actively seeking out customers to assess their needs and provide assistance. Sales associates have an emphasis on department and product knowledge, providing information on product features, and knowing related items to sell an entire project. Associates in this position know how to greet, qualify, recommend ...
Oct 2 -
MORRISTOWN - Everything else
We are looking for someone who is dedicated, responsible, and a hard worker. A minimum of one year experience in a warehouse environment is preferred....
Sep 15 - Powell, TN
Oct 2 -
KNOXVILLE - Everything else
CEVA Logistics, one of the world's leading supply chain companies, designs and implements industry leading solutions for large and medium-size national and
Sep 24 - Knoxville, TN
Oct 2 -
Vonore - Construction & trades
Reports any violations or hazards to management immediately.• Operates assigned warehouse equipment in performing the functions of the job• Participates in...
Sep 1 - Knoxville, TN
Sep 25 -
Vonore - Construction & trades
Receives transfers back into the warehouse with a logging system. Performs transfers from the warehouse area to the units during the business day....
Aug 10 - Knoxville, TN
Forklift Operator
A local leading organization is currently seeking experienced Forklift Operators in Knoxville for a long-term temporary-to-hire opportunity. Forklift positions require candidates to drive within the warehouse, moving product as well as loading and unloading trucks. If you meet the qualifications listed below, click Apply Now!Responsibilities for forklift roles include but are not limited to:- ...
Sep 24 -
Knoxville - Everything else
Jun 26 - Knoxville, TN
General Warehouse
At Work Personnel is currently hiring seasonal warehouse workers for a client located in Sevierville. Job Duties include: Assembly Packing Production Employees must feel comfortable working on their feet for 12 hour shifts and performing repetitive tasks and motions. Schedule is Monday - Friday 6: 00am-6: 00pm Pay rate is $9.00 per hour These positions are seasonal and will end in November ...
Sep 24 -
SEVIERVILLE - Everything else
Previous warehouse experience preferred. Prepares and/or assembles products for stocking orders in the warehouse and completes personalized label orders for...
Aug 20 - United States
Job Responsibilities• Inspects, fills and stages orders in accurate, thorough and efficient manner in accordance with established Company standards and procedures. Understands unit of measure.• Inspects merchandise to include checking for shortages and rejecting damaged goods.• Communicates shortages of merchandise through proper channels to ensure accurate billing.• Receives, stocks, and re ...
Sep 23 -
Knoxville - Everything else
The Warehouse Worker job responsibilities will include, but not limited to:. The Warehouse Worker receives and ships Supermicro products and coordinates...
Aug 4 - United States
Operations Director
Primary Job Responsibilities may include, but not limited to:
Responsible for the execution of the daily operating plan and management of warehouse and transportation processes which facilitate the optimal use of resources (human and automated) to achieve internal/external customer satisfaction, productivity, schedule adherence and economic goals.
Supervise the activities of workers ...
Sep 18 -
Louisville - Everything else
The Warehouse Specialist performs a variety of warehousing duties that require an understanding of the establishment s storage plan....
Jul 21 - United States
Sep 18 -
Vonore - Construction & trades
Assist other warehouse workers in completing tasks as requested by the Warehouse Manager or immediate supervisor. Visit our website at:....
Sep 25 - Tennessee
Sep 8 -
Vonore - Construction & trades
Jul 30 - Knoxville, TN
The stand worker / runner will assist in any aspect of the concessions stands/bars when necessary. Essential Tasks & Responsibilities:....
Aug 15 - Knoxville, TN
Building construction, warehouse, and/or millwork experience. Workers will install fixtures and complete other construction duties required in new-store setup,...
Jul 23 - Tennessee
The Warehouse Services II worker will lead teams of up to five (5) other Warehouse Services workers and maintain accurate documentation of warehouse records,...
Sep 30 - Tennessee
Sep 30 - Knoxville, TN
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text:
Eagles wide receiver DeSean Jackson was a guest on the NFL Network and he didn't have a problem being honest about what he thinks about Tim Tebow as an NFL quarterback.
"Forty-six percent (completion percentage)? This is not basketball, that is not good enough," Jackson said, via Larry Brown Sports. "He has the mentality to come in and be a leader and all that good stuff, but as far as winning the games throughout the whole season, I don't know. I don't know if he can be my quarterback."
Jackson managed to slihtly praise Tebow.
"He won a playoff game, he beat the (Pittsburgh) Steelers," Jackson said. "He's done a pretty good job in the playoffs, that's what I can say about him. As far as a consistent season, going throughout the whole year — he's not consistent."


text:
Company Overview of A. H. AlSagar & Bros.
Executive Profile
Hamad Abdulaziz Al Hamad Al Sagar
Owner, A. H. AlSagar & Bros.
|Total Calculated Compensation
|This person is connected to 3 Board Members in 3 different organizations across 5 different industries.
See Board Relationships
Mr. Hamad Abdul Aziz Al Hamad Al Sagar is a Co-Owner and the Managing Partner of A. H. AlSagar & Bros. Mr. Al Sagar has extensive experience in banking industry especially in Corporate Credit. He serves as the Vice Chairman of SHUAA Capital PSC and has been its Director since September 2000. Mr. Al Sagar has been a Director of National Bank of Kuwait S.A.K.P. since 1983 and serves as a Director of The National Bank of Ras Al-Khaimah (P.S.C.) and Al Kout Industrial Projects ...
Corporate Headquarters
Shuwaikh Pepsi Cola street Plot 40Phone: 965 2432980
Safat, -- 13003
Fax: 965 4811155
Board Members Memberships
Director, Chairman of Credit Committee and Member of Corporate Governance Committee
Vice Chairman
Bachelor's Degree
University College Dublin
Other Affiliations
Annual CompensationThere is no Annual Compensation data available.
Stocks OptionsThere is no Stock Options data available.
Total CompensationThere is no Total Compensation data available.
|There is no Competitor Compensation data available.
Sponsored Financial Commentaries
Sponsored Links
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To contact A. H. AlSagar & Bros., please visit . Company data is provided by Capital IQ. Please use this form to report any data issues.
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Our data partners will research the update request and update the information on this page if necessary. Research and follow-up could take several weeks. If you have questions, you can contact them at firstname.lastname@example.com.


text:
Tamarack RV Park
Today:Open 24 Hours
3630 N Government Way,
Coeur D Alene, ID 83815
(208) 714-4481
Business Details
in Business
Enjoy the beauty and serenity of North Idaho
- Hours:
Regular Hours
- General Info:
- Tamarack RV Park is nestled in the tall pines within the beautiful city of Coeur d'Alene. It has the natural, woodsy feel of forest camping in the shade of the tall ponderosa pines, combined with the convenience of nearby shopping, dining, and entertainment.We don't maintain a camp store as we would be competing with Safeway, Costco, Sportsman's Warehouse, and Home Depot all within a five minute walk. Restaurants, bowling, antique malls, and banks are all within a leisurely walk. Coeur d'Alene Lake is three miles south and Silverwood Theme Park is 15 miles north. We have very easy access less than half a mile from both Interstate 90 and State Route 95. (see map)We offer full service pull-through RV sites, tent camping, tepees, cabins and guest houses. Whatever your style of vacationing, come stay with us and enjoy the beauty and serenity of North Idaho. We are open year around.We now we have Cabins! 1) The Cowboy Bunkhouse, a one bedroom cowboy-themed cabin. 2) The Lumberjack, a fancy camping shed, with 3 bunk beds and a queen bed, plus the convenience of kitchen sink and frig and a toilet and bathroom sink and 3) Tamarack House, a three bedroom vacation rental.Some of the nearby activities include:* Golf Courses* Antique Malls* Fishing* Parasailing* Wind surfing* Water Skiing* Boating/Sailing* Canoeing & Kayaking* Horseback Riding* Theater* Museums* Fine Restaurants* Hiking & Biking Trails* Boat & Lake Cruises* Scenic Helicopter ToursCall and reserve your spot today!
- Services/Products:
- Bank Checks
- Boating Facilities
- Hiking Trails
- Locally Owned
- Pet Friendly Hotels
- References Available
- Senior Discount
- Volume Discount
- Payment method:
- debit, master card, visa, cash, check
- Accreditation:
Insured Licensed
- Other Link:
- Categories:
- Campgrounds & Recreational Vehicle Parks, Recreation Centers, Resorts, Lodging, Camps-Recreational


text:
Tadika Khalifah Comel Jawatan Kosong Pembantu Guru September 2015
Pembantu Guru Tadika Khalifah Comel
Tadika Khalifah Comel provide terms, conditions and specifications of the Job as Pembantu Guru which will be placed in Melaka
Below are the complete of requirements, job specifications, schedule of interviews and addresses and contact (email or phone number) of The Company.
Company : Tadika Khalifah Comel
Location : Melaka
City :
State : M04
Country : MY
Published at : Mon, 10 Aug 2015 11:14:40 GMT
Job Description
If You interested and meet the requirements please submit your application immedietly :
To submit your application by online, click on the link labeled with Apply Click Here or Apply This Job at the bottom of this Job vacancy information. Hopefully you get your dream Job….!
Notes :
- Kindly note that applying to this job also means that your application will be forwarded to employers with similar job vacancies available.
- If you do not wish for your resume to be forwarded to other employers, please do not apply to this job vacancy.
- Only shortlisted candidates will be notified
More Jobs Available :
- Jawatan Kosong Enterprise Solution Spec II(IMWM) Oktober 2015
- Jawatan Kosong Professional Medical Representative Oktober 2015
- Jawatan Kosong Senior Analyst, Credit Review Oktober 2015
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- Jawatan Kosong Promoter - Aeon Sunway Oktober 2015
- Jawatan Kosong Executive, QHSE & Security Oktober 2015
- Jawatan Kosong ADMIN cum PA Oktober 2015
- Jawatan Kosong Data Entry-Damansara-Immediate Hiring! Oktober 2015
- Jawatan Kosong Application Consultant Oktober 2015
- Jawatan Kosong Account Officer *German MNC* Mon-Fri~Up to 2.5K @ Empire Subang Oktober 2015
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Bradley William "Brad" Boyt
Learn about removing the ads from this memorial...
May 10, 1986
Dec. 21, 2008
Bradley "Brad" William Boyt, 22, of Johnston City, formerly of Harrisburg, died Sunday, Dec. 21, 2008 after sustaining injuries in an automobile accident on old Route 13.
Funeral services will be held 11 a.m. Saturday, Dec. 27, 2008 at Riggin-Pillatsch and Burke Funeral Home in Carterville with the Rev. Ralph Brandon officiating. Burial will be in Willowrest Cemetery in Carterville. Visitation will begin at 5 p.m. Friday, Dec. 26, 2008 at the funeral home.
Memorial contributions may be made to St. Jude Children's Hospital, Memorial and Honor Program, 501 St. Jude Place, Memphis, TN 38105-1942. Envelopes will be available at the funeral home.
Brad was born on May 10, 1986 in Herrin to Greg and Tammy (McNeill) Boyt.
He is survived by his mother, Tammy Fitzjerrells and her husband, Randy of Bonnie; father, Greg Boyt and his wife, Jacalyn of Marion; sisters, Heather McDonald and her husband Troy of Carbondale and Samantha Ciarlo of Marion; brothers, Dusty Fitzjerrells of Bonnie and Benton Fitzjerrells of Dix; grandfathers, Jay McNeill of Ferges and Charles Fitzpatrick Sr. of Harrisburg; grandmother, Deanna Boyt of Marion; girlfriend, Desiree Childers of Johnston City; and many aunts, uncles, and cousins.
Brad was preceded in death by his grandmothers, Carlene McNeill and Doris Fitzpatrick; and grandfather, Andy Boyt.
He graduated from Harrisburg High School and he attended Johnston City schools until his freshman year.
Brad had worked as a mechanic at Midwest Waste in Marion.
He was an avid outdoorsman who enjoyed hunting and fishing. He also enjoyed riding motorcycles and four wheelers. Brad was also an accomplished artist.
Willowrest Cemetery
Williamson County
Illinois, USA
Created by:
Patricia Leonberger Hoop...
Record added: Dec 25, 2008
Find A Grave Memorial# 32403861
Added by:
Lynne Johnston Westra
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Fisting an orifice so furiously that one's watch is lost during the act.
That snatch raptor shaman was just about to win until I got a Pyroblast card and rolexed him something dirty.
by treece300e August 07, 2014
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Is this restaurant good for brunch?
Does this place serve chicken wings?
Is this restaurant good for breakfast?
Does this restaurant serve Cuban food?
Does this restaurant accept reservations?
Does this restaurant serve Caribbean food?
Does this place serve pizza?
Does this place serve sandwiches?
Is this restaurant good for business?
Is this restaurant good for couples?
Thanks for helping!
What a nice surprise. Don't expect flash decor or obsequious wait staff but you can expect good drinks and good Cuban food at a fair price. If you want to try good Cuban food and don't want to pay a King's ransom, El Tropical is an excellent choice.
First time trying their food and very tasty. Staff was attentive and made sure we liked our food and beverages. Just needs a little work on greeting tables when sat to at least acknowledge the patrons otherwise great food. Will probably return.
Have eaten here many times and have seen the decline of the only Cuban restaurant in Sunny Isles beach. When I am away from Cuban food, it is the first place I come to... Please go to the nearest Cuban Restaurant and improve your version of Vaca Frita. If you love this dish as much as I do, here are...
Decent and honest Cuban food in this seaside location. The Yuca on the side was very good. Rice and beans not so much. Cubano sandwich was good as well.
Waither make a good Service, but main person in charge to The restaurant do not hace good aptitud With The Customer.
The food is quite good. There is a special menu with very reasonable prices, the remaining of the menu not being inexpensive.
We tried the arroz com leche, but it was not one of the best ones we had. We should have sticked with the internet-suggested flan.
I was there on a Monday afternoon, close to 7pm. The food was average, with good presentation, and the service was friendly and attentive. I would go back on another occasion.
We had eggs, sausage, potatoes and pastries with cafe latte and orange juice every morning for three days at this fabulous little place! The coffee and orange juice alone are worth the trip. The OJ is pricey @ $5. 89 but it is fresh squeezed and you can get it with carrots for little extra i think. The coffee is...
We eat there regularly and take visitors from out of town there. Our visitors are always impressed! We can walk there from where we live. There is a large parking lot if you are driving, You usually can find a space to park near the restaurant. Most of the time we go in the evening, however, we have gone at...
came here for breakfast, my first day in Sunny Isles. $30.00 for 3 breakfast items, plus coffee and juices. Breakfast was yummy Cuban breakfast. Service was quick and efficient.
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"Excuse me, mamma; I am not in a kissing humour."
And so Vixen left her.
Mrs. Tempest sat by the fading fire, and cried herself into a gentle slumber. It was very hard. She had longed to pour the story of this second courtship--its thrilling, unexpected joys, its wondrous surprises--into a sympathetic ear. And Violet, the natural recipient of these gentle confidences, had treated her so cruelly.
She felt herself sorely ill-used; and then came soothing thoughts about her trousseau, her wedding-dress, the dress in which she should start for her wedding-tour. All things would of course be chastened and subdued. No woman can be a bride twice in her life; but Mrs. Tempest meant that the trousseau should, in its way, be perfect. There should be no rush or excitement in the preparation; nothing should be scamped or hurried. Calmness, deliberation, and a faultless taste should pervade all things.
"I will have no trimming but Valenciennes for my under-linen," she
Vixen's mom gets married to a man Vixen detests which results in a lot of conflict.
Cara Devon has always suffered curiosity and im... Read more
When the economic downturn ends Matty Cruzs co... Read more
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Town Square
Making merry with the arts
Original post made on Dec 13, 2010
Read the full story here Web Link posted Friday, November 26, 2010, 12:12 PM
Comments (1)
a resident of another community
on Dec 13, 2010 at 12:56 pm
csma is a registered user.
Community School of Music and Arts (CSMA) is also offering a Holiday Concert! Join us to hear the most accomplished CSMA students playing a program of holiday music, multi-cultural music and assorted classical favorites. Suitable for music lovers of all ages! FREE ADMISSION!
Friday, December 17, 7 pm.
First-come, first-served seating available (approx 200+).
CSMA is located at 230 San Antonio Circle, Mountain View, 94040
For info: 650-917-6800.
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Vernon Baumgardt
VERNON 'BABE' BAUMGARDT, 89 STERLING - Vernon "Babe" Baumgardt, age 89, of Sterling, Illinois formerly of Chadwick, Illinois, died on Thursday, July 4, 2013 at CGH Medical Center, Sterling with loving family members at his side. Vernon was born on October 21, 1923, the son of George and Luella (Traum) Baumgardt in Milledgeville, Illinois. He attended school in Milledgeville, until he began helping his father haul milk. Vernon proudly served his country in the United States Army as an Infantryman during
World War II
. Vernon married Lola A. Miller-Knutti on October 23, 1971 in Chadwick. Vernon drove truck his entire life, starting with his father and later with Q-Line Trucking in Chadwick. Eventually, Vernon obtained his own milk route and hauled milk until retiring in 1988. Vernon and his wife loved traveling, especially to Branson, Missouri. They also took several trips to Florida with their children and grandchildren. He enjoyed woodworking and loved spending time with his family and friends. Vernon will be missed by his wife, Lola of Sterling; six children, Roger (Connie) Knutti of Lanark, Illinois, Larry (Char) Knutti of Pecatonica, Illinois, Steve (April) Knutti of Chadwick, Mark (Deb) Knutti of Sterling, Dave (Kalah) Knutti of Chadwick and Rick (Janet) Baumgardt of Chadwick; one daughter in-law, Shirley Knutti of Milledgeville and grandchildren, great-grandchildren, great-great-grandchildren that number up to 60. Vernon was preceded in death by his parents; one brother, Henry Baumgardt and two children, Marvin Knutti and Lana Thulen. A funeral service will be held 11 a.m. Saturday, July 6, 2013 at Hope United Methodist Church in Chadwick. Burial will take place in the Chadwick Cemetery, Chadwick. Military Rites will be accorded by the Chadwick American Legion. A visitation will be held from 10 to 11 a.m., prior to the service at the church. A memorial fund has been established in Vernon's memory. Online condolences may be left for the family at
Published in The Journal-Standard from July 6 to July 7, 2013


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Posted November 17, 2012 on AP on Fox
CHARLOTTE, NC - MAY 02: Rory McIlroy of Northern Ireland tee's off at the 13th during the final round of the Quail Hollow Championship at Quail Hollow Country Club on May 2, 2010 in Charlotte, North Carolina. (Photo by Richard Heathcote/Getty Images)
Rory McIlroy has vowed to cut back his competitive schedule next year after the disappointment of missing the cut in his defense of the Hong Kong Open. The world's top-ranked golfer four-putted the final green Friday to finish three shots off. It marks the second time this year the 23-year old has had to sit out the weekend rounds in the defense of a tournament after also missing the cut in June's U.S. Open at San Francisco. Before leaving Hong Kong for Dubai and the season-ending World Tour Championship, McIlroy said he's learned a further lesson and will spend the coming weeks working out where he'll compete in 2013. ''Of course, you're going to miss cuts in your career, but it's not nice and it's a tough pill to swallow when you're the defending champion in a tournament,'' the Northern Irishman said. ''While there's a part of me that perhaps wished my year had ended as soon as I wrapped up the Race to Dubai, I now look back over the last couple of years wondering why did I s...
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The University of Georgia has been named one of the "Super 11" sports communications departments in the NCAA Football Bowl Subdivision for the 2013 season by the Football Writers Association of America (FWAA).
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SANTA FE, N.M. (AP) — The state Human Services Department will begin automatically signing up students for free and reduced lunches each month.
Human Services Department Secretary-designate Kathryn Falls said Wednesday children enrolled in the Supplemental Nutrition Assistance or the Temporary Assistance for Needy Families programs qualify for the National School Lunch Program.
Falls says checking for new children participating in those federal programs each month will allow more students to get free and reduced lunches.
Since 2003, the department had checked for eligible children once a year.
But with the number of families seeking federal assistance growing, the department says it must increase the search for students who have just become eligible.
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Communications Equipment
Company Overview of Navigation Solutions, LLC
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text: Support 88Nine And This Artist: Buy On Amazon Buy On iTunes Yeasayer is a band based in Brooklyn, New York. The band was formed in 2006 and consists of three core members, Chris Keating, Ira Wolf Tuton, and Anand Wilder. They first came to attention after appearing at the SXSW festival in early 2007. Their debut album All Hour Cymbals was released in October 2007. Yeasayer described their music as "Middle Eastern-psych-snap-gospel". Live performances often include psychedelic visuals. Yeasayer released their second studio album, Odd Blood, in February 2010, featuring more pop music influences than earlier work. The band revealed that the album came out of a massive acid trip in New Zealand. Peter Gabriel's drummer Jerry Marotta helped to record Odd Blood in an upstate New York studio packed with rare synths and percussion instruments from around the globe to create the characteristic worldbeat sound of the album. Yeasayer released their third studio album, Fragrant World, in August 2012. According to the Fingers Never Bleed Songfacts, it was named after a track that didn't make the new album's final cut. Read more on Last.fm. User-contributed text is available under the Creative Commons By-SA License; additional terms may apply. Tracks We Played Longevity iTunes Longevity Fragrant World Last Played on April 09, 2014 10:56am AMBLING ALP iTunes AMBLING ALP Odd Blood SUNRISE iTunes SUNRISE All Hour Cymbals I REMEMBER iTunes I REMEMBER I REMEMBER (EP) CRAZY iTunes CRAZY Crazy (Single) FINGERS NEVER BLEED iTunes FINGERS NEVER BLEED Fragrant World ROME iTunes ROME Odd Blood View the discussion thread.


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Artist: Bathory
Album: Miscellaneous
Genre: Rock
Going to school she learned to read and write
So much is new and life's full of wrong and right
Homework is done life has just begun
Hello world here's daddy's girl
Waking up early morning living in her own place
Taking a shower staring in the mirror at a tired face
Something for breakfast doing her face
Feeding her pet just like every other day
Still she isn't knowing when she's locking the door and going to her work
That in the morning next day she won't sleep alone
Later on in the evening she'll be riding on a feeling
Still she's somehow gonna be needing just a beer more or two
Daddy's girl, here's daddy's little girl
Daddy's girl, here's daddy's little girl
Party and music feels like this night could last a lifetime
Ain't gonna lose this feeling tonight she'll leave it all behind
A kiss and a hug from one of those guys
But she leaves with another in a cab in the night
Unlocking the door she's weary she can feel his heavy breathin'
Not too sure if she's still playin' a game or if she really feels like screwing
Is this really loving she is feeling really nothing
Still she is letting him proceed with whatever that is he is doing
Daddy's girl...
A kiss and a hug from one of those guys
But she leaves with another in a cab in the night
Who thinks of protection or the choice of rejection
When he is just about all done and her head is dizzy from all the free beers
Daddy's girl...
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|Publication number
|Publication type
|Application number
|Publication date
|Nov 6, 1984
|Filing date
|Mar 7, 1984
|Priority date
|Mar 7, 1984
|Fee status
|Publication number
|Fadia E. Ali, William F. Huffman
|Original Assignee
|Smithkline Beckman Corporation
|Export Citation
|BiBTeX, EndNote, RefMan
|Patent Citations (2), Referenced by (13), Classifications (14), Legal Events (6)
|External Links: USPTO, USPTO Assignment, Espacenet
This invention relates to cyclic heptapeptides which have vasopressin antagonist activity. More specifically, these new chemical compounds have structures which are characterized by the lack of both a prolyl unit at position 7 and a glycyl unit at position 9 of the 1-Pmp-VSP antagonist structure.
M. Manning, W. H. Sawyer and coworkers have published a series of papers describing various [1-(β-mercapto-β,β-cyclopentamethylenepropionic acid)-4-valine]-arginine-vasopressin congeners which have antivasopressin activity. Representative of these are EPA No. 61,356, U.S. Pat. Nos. 4,367,225 and 4,399,125.
All of the Manning compounds have a tripeptide chain attached at unit 6 of the 6-unit dithio ring and are, of course, nonapeptides. The present compounds are distinguished over these by being des-Pro7 des-Gly9 vasopressins yet having substantial antagonist activity.
Also, a previously filed U.S. patent application, Ser. No. 467,117 filed Feb. 16, 1983, discloses certain octapeptide vasopressin congeners which have the 9-Gly unit deleted and which have potent VSP antagonist activity.
All of the previously disclosed compounds have structures which have an essential proline-like unit at position 7 of VSP. The compounds of this invention have no such unit in their structures and have substantial VSP antagonist of aquaretic activity.
In the description herein and in the claims, the nomenclature common in the art of peptide and vasopressin chemistry is used. When no configuration is noted, the amino acid unit is in the L, or naturally occuring, form. In certain structural formulas, the thio members of the Pap and Cys units are added for clarity.
Certain of the peptide art designations used herein are the following: Pap, β-mercapto-β,β-cycloalkylenepropionic acid; Pmp, β-mercapto-β,β-cyclopentamethylenepropionic acid; Abu, β-aminobutyric acid; Chg, cyclohexylglycine; Cha, cyclohexylalanine; Pba, aminophenylbutyric acid, Gln, glutamic acid amide; Gly, glycine; Tyr, tyrosine; Phe, phenylalanine; Val, valine; Ile, isoleucine; Nle, norleucine; Leu, leucine; Ala, alanine; Lys, lysine; Arg, arginine; Asn, asparagine; Tos, tosylate; BHA, benzhydrylamine; DIEA, diisopropylethylamine; 4-MeBzl, 4-methylbenzyl; TFA, trifluoroacetic acid; DCC, dicyclohexylcarbodiimide; HBT, hydroxybenzotriazole; ACM, acetamidomethyl.
The des-Pro-des-Gly-VSP compounds of the invention are illustrated by the following structural formula: ##STR1## in which: P is Phe or Phe(4'-Alk);
X is D-Phe, D-Val, D-Nva, D-Leu, D-Ile, D-Pba, D-Nle, D-Cha, D-Abu, D-Met, D-Chg, D or L-Tyr or D or L-Tyr(alk);
Y is Val, Ile, Abu, Ala, Chg, Gln, Lys, Cha, Nle, Phe, Leu or Gly;
Z is D-Arg, L-Arg, D-Lys or L-Lys;
A is OH, NH2 or NHAlk;
n is 0-2, or pharmaceutically acceptable salts, prodrug esters or complexes thereof.
"Alk" in formula 1 and hereafter represents a lower alkyl of 1-4 carbons which is optionally attached either to the nitrogen at A, to the oxygen substituent of the tyrosine unit when the latter is present at position 2 or at the 4'-position of Phe at position 3. Such alkyl substituents include methyl, ethyl, n-propyl, isopropyl or butyl. Preferably Alk is methyl or ethyl. "Bzl" represents benzyl.
When the term, "vasopressin" or "VSP" is used, it means L-arginine vasopressin (AVP) unless otherwise modified to indicate a D-arginine, D-lysine or L-lysine vasopressin. The AVP derivatives of this invention are preferred. In the compounds represented by formula I, those with structures having A as NH2 are also preferred for VSP antagonism.
A subgeneric group of compounds of this invention comprises compounds of formula I in which P is Phe, X is D-Tyr(Et); Y is Val or Abu; n is 1; Z is L-Arg and A is NH2.
Also included in this invention are various derivatives of the compounds of formula I such as addition salts, prodrugs in ester or amide form and complexes. The addition salts may be either salts with pharmaceutically acceptable cations such as NH4.sup.⊖, Ca ++ , K.sup.⊖ or Na.sup.⊖ at the terminal acid group or with a pharmaceutically acceptable salt at a basic center of the peptide (as in the Arg units). The acetate salt forms are especially useful although hydrochloride, hydrobromide and salts with other strong acids are useful. The compounds, also, form inner salts or zwitter ions as when a terminal carboxy group is present. Prodrugs are simple derivatives of the compounds of formula I which degrade in vivo to give the parent compound. The ester prodrug forms are, for example, lower alkyl esters of the acids of formula I which have from 1-8 carbons in the alkyl radical or aralkyl esters such as various benzyl esters. Other latentiated derivatives of the compounds of formula I will be obvious to those skilled in the art. "Complexes" include various solvates such as hydrates, alcoholates or those with supporting resins, such as a Merrifield resin.
The compounds of formula I are prepared by cyclizing a linear heptapeptide intermediate of this invention by means of the two mercapto groups located, respectively, at the cysteine unit at position 6 and the β-mercapto-β,β-cyclopolyalkylene-propionic acid unit (Pap) at position 1. The cyclization reaction occurs in the presence of a mild oxidizing agent which is capable of oxidizing a mercaptan to a disulfide.
For example, oxidation of the following linear heptapeptide; ##STR2## in which P, X, Y, Z, and A are as defined for formula I, with the mercapto groups (--SH) being members of the Pap and Cys units, is carried out as described generally above. For example, an excess of an alkali metal ferricyanide, such as potassium or sodium ferricyanide, is used, with the linear intermediate dissolved in a suitable unreactive solvent, preferably in an aqueous solvent, at a neutral pH, about 7-7.5, at ambient temperature, or lower, until the reaction is substantially complete. Preferably, the concentrations of the linear peptide dimercaptan and the oxidizing agent are low, say 0.01 molar concentration of oxidizing agent in several liters of aqueous solution to cyclize 1-5 grams of dimercaptan. Other solvents may be added especially methanol, ethanol or isopropanol.
Other mild oxidation agents having an oxidation potential roughly equivalent to ferricyanide may also be used for the ring closure reaction. Oxygen, diiodoethane or iodine are alternatives. Of course, one skilled in the art will recognize that certain cyclization methods are not appropriate if an interfering reaction site is present in the structure of the starting material of formula II. The linear mercaptan starting material may or may not have protecting groups common to the art present at the various amino acid units or at the mercapto positions. In the former case, the protecting groups are removed after cyclization. In the case of the ACM-SH protecting groups, removal of the protective group and cyclization are both accomplished using iodine in aqueous methanol. Usually, however, the free linear peptide is cyclized.
The desired cyclic des-proline des-glycine peptide of formula I is conveniently isolated by acidifying the aqueous oxidation mixture, such as using glacial acetic acid, and passing the reaction mixture over an ion-exchange chromatographic column, for example, over a weakly acid, acrylic resin column with acid elution, or by gel filtration over a bead-formed gel prepared by cross-linking dextran with epichlorohydrin.
In an alternative reaction sequence for preparing the compounds of this invention, for example, the intermediate of formula II in which the Arg(NH2) unit at position 7 is missing is cyclized as described above and the resulting Cys acid is, then, condensed in a N-protected Arg(NH2) derivative, such as a protonated derivative, or Arg(NH2) itself. Reaction conditions for the tail unit attachment are those of any amide producing method known to the peptide art but, particularly, reaction of an amino acid or amide (NH2 -Z-A) whose carboxylic acid group, if present, is protected, as described below, with the 6-Cys acid in the presence of DCC and HBT is used. The protecting groups which may be present on the cyclic Cys acid or on the tail unit are, then if present, removed to give the products of this invention. Reaction conditions should be selected to minimize racemization of the Cys unit as known to the art.
The important intermediates of formula II, in free or protected form are conveniently prepared using solid-phase methods of peptide synthesis as discussed in M. Manning et al., J. Med. Chem. 25 46 (1982). A commercial benzhydrylamine support resin (BHR) is used to prepare the end products of formula I in which A is NH2 (the amides) and a chloromethyl support resin (CMR) is used to prepare the compounds of formula I in which A is OH (the acids).
The peptide chain of the linear peptides of formula II is built up, stepwise, proceeding from unit 8 working toward unit 1. Each unit is properly protected as known in the peptide art and as described below. The sequence of step reactions is conveniently carried out in a Beckman 990B peptide synthesizer without isolation of each intermediate peptide. The details of the procedure are in the working examples presented hereinafter.
The various amino acids, which are consecutively added to the resin supported chain are protected as known to the art. For example, the Boc protecting group is used for an amino group especially at the α-position; benzylthiomethyl, ethylcarbamoyl, adamantyl, t-butyl, acetamidomethyl, trityl or an optionally substituted benzyl, for the mercapto groups at the Pap and Cys units; nitro; carbobenzoxy, methylene-2-sulfonyl or tosyl for the Arg unit; and ethyloxycarbonyl or an optionally substituted carbobenzoxy (Z) for the Tyr or Lys units. The protective groups should, most conveniently, be those which are easily removed, that is, using acid treatment for the tert.-butyloxycarbonyl (Boc) group, sodium-liquid ammonia or modified catalytic hydrogenation for the benzyl or carbobenzoxy groups.
The protected linear peptide intermediate is split from the carrying resin matrix, for example, by using ammonia in an aqueous miscible solvent, and, then, is treated to remove the protective groups, such as by using sodium-liquid ammonia. This procedure gives the amide derivative of the linear heptapeptide.
More conveniently, the two steps are combined by treating the resin supported peptide with anhydrous hydrogen fluoride (HF) in a suitable organic solvent, such as anisole, to give the des-proline peptide intermediate of formula II in good yield.
The compounds of this invention have potent vasopressin antagonist activity. Vasopressin is known to contribute to the anti-diuretic mechanism of action within the kidney. When the action of these compounds antagonizes that of the natural anti-diuretic hormone (ADH), the body excretes water due to an increased permeability of the terminal portions of the renal tubule. We believe the mechanism of action is at the vasopressin receptors [V2 -receptors] located on the plasma membrane of certain renal epithelial cells. The most notable pharmocodynamic effect of the ADH antagonists of the invention is that of a water diuretic rather than of a natriuretic such as a thiazide.
Any patient suffering from the syndrome of inappropriate antidiuretic hormone secretion (SIADH) or from an undesirable edematous condition is a target for the claimed compounds. Examples of clinical conditions indicated for the compounds of this invention include hypertension, hepatic cirrhosis, congestive heart failure or a component of any traumatic condition resulting from serious injury or disease.
The second group of vasopressin receptor sites are the vascular pressor sites (V1 -receptors) within the cardiovascular system itself. These may also be somewhat antagonized by the compounds of this invention. Dysmenorrhea is another utility for the compounds of this invention when administered intravenously or intranasally.
The compounds of this invention, therefore, are used to treat edema or to expell water in patients in need of such treatment by administering internally, particularly parenterally or by insufflation, a nontoxic but effective quantity of the chosen compound, preferably combined with a pharmaceutical carrier. Dosage units of the active ingredient are selected from the range 0.05 to 20 mg/kg, preferably 1 to 5 mg/kg, based on a 70 kg patient. The dosage units are administered from 1 to 5 times daily.
The pharmaceutical composition which contains an active ingredient of formula I comprises a dosage unit as described above dissolved or suspended in a standard liquid carrier, such as isotonic saline, contained in an ampoule or a multiple dose vial suitable for a parenteral injection such as for intravenous, subcutaneous or intramuscular administration. A composition for insufflation may be similar but is usually administered in a metered dose applicator or inhaler. Pulverized powder compositions may, also, be used along with oily preparations, gels, buffers for isotonic preparations, emulsions or aerosols.
Antagonistic activity toward the natural antidiuretic hormone (anti-ADH activity) is determined, in vitro, in the medullary tissue of hog or human kidneys and, in vivo, in the hydropenic rat. The in vitro assay procedures for vasopressin stimulated adenylate cyclase activation or vasopression binding activity are described by F. Stassen et al., J. Pharmacology and Experimental Therapeutics, 223, 50-54 (1982).
In the test procedure for assay of adenylate cyclase activity, the amount of 32 P/cAMP formed in the absence of medullary membrane is determined (blank). The blank value is subtracted from all experimental data. The compound is tested for its effect on basal adenylate cyclase activity and/or on vasopressin stimulated activity. Each determination is carried out in triplicate. The Ka value is derived from a Lineweaver-Burke plot. Rel. Vmax =(Vmax drug/Vmax vasopressin)�100. Ki =I/[Ka'/Ka)-1] where I is the concentration of the antagonist, and Ka' and Ka are the concentrations of vasopressin required to give half maximal activity of adenylate cyclase in the presence and absence of antagonist, respectively.
In the test procedure for binding assays, the amount of 3 H-vasopressin bound in the absence and in the presence of an excess of vasopressin (7.5�10-6 M) is measured in triplicate. These values represent total and non-specific binding, respectively. The KB of a compound is derived from the equation for competitive inhibition: KB -IC50 /(1+L/KD), where IC50 is the concentration required for 50% inhibition of 3 H-vasopressin (KD =3.6�10-9 M; 1 SD=0.4�10-9 M). This is the average KD value determined on 3 preparations of hog kidney membranes.
The assay for anti-ADH activity is the hydropenic rat protocol is described below:
Food and water are removed from male rats approximately 18 hours prior to testing. Animals are housed 4 per metabolism cage. At 0 hour, the test compound is administered intraperitoneally to the test group and an equivalent volume of vehicle is administered to both control groups (fasted and non-fasted). Urine volume and osmolality are measured every hour for 4 hours. Test values are recorded as ml of urine excreted (cumulative), mEq/rat electrolyte excreted, mg/rat urea excreted, and osmolality in milli-Osmoles/kg H2 O. A tolerance test is used to determine significance. ED300 is defined as the dose of compound (μg/kg) required to lower urine osmolality to 300 m-Osmoles/kg.
TABLE 1______________________________________Anti-ADH Activity In Vivo (Rat) In Vitro (Pig)Compound ED300 (μg/kg)* Ki (nM) BB (uM)______________________________________A 74.6* 2.5 9.0B 121.8* 6.2 13.0C 11.0* 9.8 13.0______________________________________ (A) [1(mercapto-β,cyclopentamethylenepropionic acid)2-(O--ethylD-tyrosine)-4-valine-7-desproline-8-arginine-9-desglycineasopressin (B) 1(mercapto-β,cyclopentamethylenepropionic acid)2-(O--ethylD-tyrosine)-4-aminobutyric acid7-desproline-8-arginine-9-desglycinevasopressin (C) [mercapto-β,cyclopentamethylenepropionic acid)2-(O--ethylD-tyrosine)-4-valine-8-argininevasopressin *Estimated dose of peptide delivered ip stat (μg/kg) which results in reduction of Uosm from hydropenic levels to 300 mOsmoles/kg H2 O.
The following examples are intended solely to teach the preparation of the compounds of this invention. All temperatures are in degrees Centigrade.
For the solid phase synthesis of the titled resin-supported peptides, Boc. Arg(Tos)BHA resin (1.34 mmol/g of resin) was used as a starting material. It was prepared by reacting BOC-Arg(Tos), 3 mmol, with the benzhydrylamine resin, 1.0 mmol, in dimethylformamide for two hours. The benzhydrylamine resin as a free base was swelled in methylene chloride overnight. It was washed once with 7% diisopropylethylamine (DIEA) in methylene chloride, then 6�1 min. with methylene chloride, and finally 2�1 min. with predried dimethylformamide. The loading of BOC-Arg-(Tos) on the resin was carried out twice on the shaker using 1-hydroxybenzotriazole (HBT, 6 mmol), and dicyclohexylcarbodiimide (DCC, 3 mmol). A quantitative ninhydrin test and amino acid analysis were performed routinely after loading to determine the percentage loading on the resin. Loading in this particular run was 53%, i.e., only 0.709 mmol/g of resin was available.
The appropriately protected amino acids were coupled sequentially on the Boc. Arg(Tos)-resin using the Beckman peptide synthesizer 990-B. The program used for each coupling, except Boc-Asn and Pmp(4-MeBzl), was as follows:
(1) Washed with methylene chloride (3 times, 1 min).
(2) Prewashed with 50% trifluoroacetic acid in methylene chloride (1 time, 1 min).
(3) Deprotection with 50% trifluoroacetic acid in methylene chloride (30 min).
(4) Washed with methylene chloride (3 times, 1 min).
(5) Prewashed with 7% DIEA in methylene chloride (1 time, 1 min).
(6) Neutralized with 7% DIEA in methylene chloride (1 time, 10 min).
(7) Washed with methylene chloride (3 times, 1 min).
(8) Protected amino acid (3 mmol) in methylene chloride, followed by addition of DCC, 3 mmol, 10 ml of 0.3M in methylene chloride, and coupling for two hours.
(9) Washing with methylene chloride (3 times, 1 min).
(10) Washing with ethanol/methylene chloride (1:1) (3 times, 1 min).
(11) Washing with methylene chloride (3 times, 1 min).
In case of coupling of Asn moiety, 1-hydroxybenzotriazole (HBT, 6 mmol) was used, 10 ml of 0.6M in dimethylformamide. Dry dimethylformamide was also used as solvent when Pmp(4-MeBzl) was coupled onto the peptide resin, using 4-dimethylaminopyridine (DAP, 3 mmol). Completion of each coupling reaction was monitored by the ninhydrin test. The p-methylbenzyl group was used to protect the thiol groups of Cys and the pentamethylenemercaptopropionic acid (Pmp) moieties.
After coupling to the Asn amino acid, the resin-supported peptide was split into two halves, 0.355 mmol each, to incorporate separately Boc-Abu or Boc-Val at position 4, and the sequence was continued to Pmp (4-MeBzl) as indicated. The resulting protected peptide resin intermediates, i.e., [Pmp(4-MeBzl)-D-Tyr(Et)-Phe-Y-Asn. Cys(4-MeBzl)-Arg(Tos)-BHA, resin] where Y=Abu or Val, were washed separately with methylene chloride and dried in vacuo overnight to give 0.87 g (Y=Abu), 0.67 g (Y=Val). The latter resin was used for Example 2.
Pmp(4-MeBzl)-D-Tyr(Et)-Phe-Abu-Asn-Cys(4-MeBzl)-Arg(Tos)-BHA-resin, 0.87 g in 2 ml of anisole, was reacted with anhydrous hydrogen fluoride (20 ml) at 0� for 50 min. After evaporation in vacuo to dryness, the residue was treated with anhydrous ether, and the crude peptide was extracted with dimethylformamide (50 ml) and 33% acetic acid (60-70 ml) into a 2 liter water. The water-diluted dimercapto heptapeptide was cyclized using 0.01M potassium ferricyanide solution at pH 7.2 until color persisted for 30 min (˜30 ml). After the completion of the oxidation reaction, the pH of the solution was adjusted to pH 4.5 by adding glacial acetic acid. This solution was passed through a weakly acid acrylic resin (Bio-Rex 70) column (2.5�12 cm) slowly. The column was eluted with pyridine-acetate buffer (pyridine/glacial acetic acid/water, 30:4:66). The pyridine-acetate solution was removed by distillation in vacuo and the residue was lyophilized from 10% acetic acid to give 115 mg (33%) of crude titled peptide.
(1) Partition Column, Sephadex, G-25: sample: 115 mg, n-butanol/acetic acid/water, (4:1:5), 72.6 mg
(2) Gel Filtration, G-15, 0.2M acetic acid: 60.5 mg
(3) Preparative HPLC sample: 35.0 mg (from 2), Altex ODS, 10 mm�25 cm 5μ, flow rate 4 ml/min., water/acetonitrile/trifluoroacetic acid (60:40:0.25%), isocratic, 229 nm (2.0 AUFS), injection 4.14 mg) 500 μl. 28 mg pure sample of the titled product.
Physical Data:
Molecular Formula: C45 H65 N11 O9 S2.
Molecular Weight: 967.48.
Amino Acid Analysis: Asp (1.00), Abu+Cys (1.35), Tyr (0.74), Phe (0.93), Arg (0.82).
Peptide Content: 65.6%.
______________________________________Chromatography Data: solvent RF______________________________________Thin layer chromatography (TLC) Butanol: Acetic Acid/ 0.63 Water/Ethyl acetate (1:1:1:1) Butanol/Acetic Acid/ 0.51 Water (4:1:5) (Upper)High pressure liquid C-18 column k'chromatography (HPLC)isocratic, 0.05 M potassium/ C-18 column 4.7dihydrogen phosphate/acetoni-trile (60:40)Gradient, 0.05 potassium 15.2dihydrogen/phosphate/acetonitrile (80:20 to 50:50)Fast Atom Bombardment "FAB" : (M + H)+ at 968 (M - H)- at 966______________________________________
Pmp(4-MeBzl)-D-Tyr(Et)-Phe-Val-Asn-Cys(4-MeBzl)-Arg(Tos)-BHA-resin, 0.67 g from Example 1 in 2 ml of anisole, were reacted with anhydrous hydrogen fluoride (20 ml), at 0� for 50 min. It was worked up as in the previous example, to give 80 mg (23%) of crude titled peptide.
(1) Partition column, Sephadex, G-25: sample: 80 mg, n-butanol/acetic acid/water (4:1:5), 75.7 mg.
(2) Preparative HPLC: sample: 42.7 mg (from 1), Altex ODS, 10 mm�25 cm, 5μ, flow rate 4 ml/min, water/acetonitrile/trifluoroacetic acid (60:40:0.25%), isocratic, 229 nm (2.0 AUFS), injection 4.7 mg/500 μl, 36.8 mg pure titled sample.
Physical Data:
Molecular Formula: C46 H67 N11 O9 S2.
Molecular Weight: 981.44.
Amino Acid Analysis: Asp(1.06), Cys(0.37), Val(1.00), Tyr(0.65), Phe(0.91), Arg(1.00).
Peptide content: 87.55%.
______________________________________Chromatography Data: solvent RF______________________________________Thin layer chromatogra- n-Butanol/acetic acid/ 0.6phy (TLC) water/ethyl acetate (1:1:1:1) n-Butanol/acetic acid/ 0.516 water (4:1:5) (Upper)High pressure liquid C-18 column K'chromatography (HPLC)isocratic, 0.05 potassium 6.25dihydrogen phosphate/acetonitrile (60:40)Gradient, 0.05 potassium 16.0dihydrogen phosphate/acetonitrile (80:20 to 50:50)Fast Atom Bombardment "FAB": (M + H)+ at 982 (M - H)- at 980______________________________________
Pmp(4-MeBzl)-D-Tyr(Br-Z)-Phe-Val-Asn-Cys(4-MeBzl)-Arg(Tos)-Resin (4.0 g, prepared by the method from Example 1, in 4.5 ml distilled anisole, is treated with anhydrous hydrogen fluoride (40 ml) at 0� for one hour. After evaporation in vacuo to dryness, the residue is treated with anhydrous ether and extracted to give 1.30 g of crude peptide. The resulting unprotected heptapeptide is cyclized using 0.01M potassium ferricyanide solution at pH 7-7.5 until color persisted for 30 minutes again as described above. The titled compound is isolated and purified as described above.
A mixture of 0.1 mmole of (Pmp1 -D-Tyr(Et)2 -Val4 -desPro7 desGly9)AVP, prepared as described above, and 0.1 mmole of n-propylamine in 20 ml of dimethylformamide is reacted with 23 mg (0.11 mmole) of DCC and 14 mg (0.11 mmole) of HBT at room temperature for 2 hours. The volatiles are evaporated to give a product residue. The product is purified using (1) gel filtration over G-10-Sephadex eluted with 0.2N acetic acid, (2) high pressure liquid chromatography using 0.05% trifluoroacetic acid in 39% acetonitrile in water and, again, (3) gel filtration to give the pure peptide of the title.
Substituting a stoichiometric quantity of Boc-L-Tyr(Et) at the 2 unit of the peptide synthesis of Example 1 gives Pmp-L-Tyr(Et)-Phe-Val-Asn-Cys-Arg(NH2).
Substituting in Example 1, using CMR, D-Arg(Tos) at the 7 unit gives Pmp-D-Tyr(Et)-Phe-Val-Asn-Cys-D-Arg(OH).
Substituting Boc-L-Phe(4-Me) for the amino acid at the 3 unit and Boc-Nle at the 4 unit in the synthesizer sequence reactions of Example 1 gives Pmp-D-Tyr(Et)-Phe(4-Me)-Nle-Asn-Cys-Arg(NH2).
Substituting Boc-Nvl for the amino acid at the 4-unit of Example 1 gives Pmp-D-Tyr(Et)-Phe-Nvl-Asn-Cys-Arg(NH2).
Substituting Boc-Cha at the 4 unit gives Pmp-D-Tyr(Et)-Phe-Cha-Asn-Cys-Arg(NH2).
Substituting Boc-D-Pba at the 2 unit and Boc-Chg at the 4 unit of detailed reaction sequence of Example 1 gives Pmp-D-Pba-Phe-Chg-Asn-Cys-Arg(NH2).
Substituting in Example 1, using CMR, L-Lys(Boc) at the 7 unit, as described in the specification, gives Pmp-D-Tyr(Et)-Phe-Val-Asn-Cys-L-Lys(OH).
Substituting β-(S-benzylmercapto-β-β-cyclotetramethylene)propionic acid (Tmp) for Pmp in Example 1 gives the Tmp1 -D-Tyr-(Et)2 derivative of Example 1.
A preparation which contains 0.5 mg of the cyclic octapeptide of Example 2 as a sterile dry powder for parenteral injection is prepared as follows: 0.5 mg of peptide amide is dissolved in 1 ml of an aqueous solution of 20 mg of mannitol. The solution is filtered under sterile conditions into a 2 ml ampoule and lyophylized. The powder is reconstituted before either intramuscular or intravenous injection to a subject suffering from edema susceptible to anti-ADH mechanism of action. The injection is repeated as necessary, from 1-5 times daily or in continuous i.v. drug injection. Other octapeptides of this invention are made up and used in like manner.
340 mg of finely ground octapeptide of this invention such as the product of Example 2 is suspended in a mixture of 75 mg of benzyl alcohol and 1.395 g of a suspending agent such as a commercial mixture of semi-synthetic glycerides of higher fatty acids. The suspension is placed in an aerosol 10 ml container which is closed with a metering valve and charged with aerosol propellants. The contents comprise 100 unit doses which are administered intranasally to an edematous subject from 1-6 times a day.
|Cited Patent
|Filing date
|Publication date
|Mar 24, 1981
|Jan 4, 1983
|The Medical College Of Ohio
|Novel antagonists of the antidiuretic and/or vasopressor action of arginine vasopressin
|Nov 16, 1981
|Aug 16, 1983
|Maurice Manning
|Novel antagonists of the antidiuretic action of arginine vasopressin
|Citing Patent
|Filing date
|Publication date
|Nov 21, 1984
|Jul 8, 1986
|Smithkline Beckman Corporation
|V1-vasopressin antagonists
|Apr 23, 1985
|Apr 7, 1987
|Smithkline Beckman Corporation
|Cupric oxidation of 1,6-dimercapto-containing peptides
|Nov 19, 1985
|Aug 18, 1987
|Smithkline Beckman Corporation
|Des-proline-N-methylarginine vasopressins
|Sep 18, 1985
|Dec 8, 1987
|Smithkline Beckman Corporation
|6-pen-vasopressin compounds
|Jun 23, 1986
|Jan 5, 1988
|Smithkline Beckman Corporation
|ARG7 -ARG8 -vasopressin antagonists
|Sep 30, 1986
|Feb 9, 1988
|Smithkline Beckman Corporation
|Arg-arg-arg-vasopressin antagonists
|Oct 23, 1985
|May 3, 1988
|Smithkline Beckman Corporation
|GLN- or ASN-vasopressin compounds
|Apr 28, 1987
|Jul 26, 1988
|Smithkline Beckman Corporation
|1,6-dicarba-vasopressin compounds
|Dec 4, 1986
|Aug 23, 1988
|Smith Kline Beckman Corporation
|Tyr-Arg-vasopressin antagonists
|May 21, 1987
|May 2, 1989
|Smithkline Beckman Corporation
|4'-Methyl-β-mercapto-β,β-cyclopentamethylenepropionic acid vasopressin antagonists
|Aug 27, 1987
|Oct 24, 1989
|Smithkline Beckman Corporation
|Vasopressin compounds
|Sep 28, 1987
|Jun 8, 1988
|Smithkline Beckman Corporation
|Vasopressin antagonists
|Dec 3, 1987
|Jun 8, 1988
|Smithkline Beckman Corporation
|Vasopressin antagonists
|U.S. Classification
|International Classification
|Cooperative Classification
|European Classification
|Mar 7, 1984
Owner name: SMITHKLINE BECKMAN CORPORATION, ONE FRANKLIN PLAZA
Free format text: ASSIGNMENT OF ASSIGNORS INTEREST.;ASSIGNORS:ALI, FADIA E.;HUFFMAN, WILLIAM F.;REEL/FRAME:004237/0925
Effective date: 19840302
|Apr 16, 1985
|Certificate of correction
|Mar 28, 1988
|Fee payment
Year of fee payment: 4
|Jun 10, 1992
|Maintenance fee reminder mailed
|Nov 8, 1992
|Lapse for failure to pay maintenance fees
|Jan 19, 1993
|Expired due to failure to pay maintenance fee
Effective date: 19921108


text:
Pleasant staff. Great location.
Bathroom was dark, needed better lighting. Carpet was stained in hallways and needed to either replaced or cleaned.
I liked that the breakfast stayed open as long as it did. I was able to get a bite to eat when I woke up at 7 and then went trail running. When I got back at 1039 I was able to get seconds! And the selection was much better than other hotels.
The rooms were very small. We had a bad view would have preferred a water view but no rooms were available. If I returned I would request a water view, a must. The pools were nice indoor & outdoor. Nice resturant. Good entertainment in the evenings. Would have liked a breakfast of some sorts.
Clean rooms, clean bathroom, fun stay!!
The sliding door was hard to open on the balcony.
From check in to check out, everything was perfect. Clean, at attractive and comfortable room and a much better than average breakfast. All staff were friendly and helpful. We would definitely choose this hotel again.
Friendly desk staff at check in, pretty good selection for breakfast, kids enjoyed the pool.
Clean and professional. Bathrooms are spacious.
Breakfast bar ran out of oatmeal.
I brought 3 kids 10 and under to stay at this Baymont. They loved the pool and hot tub, and the location was close to the museum we wanted to visit. We did not try the breakfast. Did I say we loved the pool.
The sink outside the bathroom was unusual arrangement, and the undersink pipe leaked a little when using. The hotel could use a facelift. Theres no elevator to 2nd floor.
The breakfast was small but it had a waffle maker, and they had HBO in the room.
Not enough outlets, the way they had the room setup with wall adapters and extension cords made it feel like a fire hazard. The alarm clock made a noise when the phone was next to it. The room smelled of stale smoke, and there was cigarette burns in the linen.
Staff very friendly, proficient and accommodating. Very clean.
Pillows were small throw pillows. Insufficient electrical outlets.
Not sure
Too many things to mention here
The room where we were was comfortable enough for the price we paid and also considering we were there only on night, it was not bad at all. We did not have any expectations to start with in this place and were looking for a place to just sleep for the night.
Needs a better breakfast room and variety. Staff is not friendly.
The staff was very friendly and nice.
The prices were very high for a perfectly normal and acceptable hotel room.
Hot tub & pool
Check-in was nothing short of positive. I had used the Kayak app on my phone, not realizing I had the wrong dates. When I went to check-in, the young lady did everything to find a room, which was tough. Electric Forest was the next day. I was placed in a room, and didn't pay a cent extra.
Great experience overall. The continental breakfast was lacking, but I'm not big on hotel breakfasts.
It was run down and needed cleaning.
Nice sized pool and hot tub kept at reasonably hot level. Fast internet, decent breakfast, no real protein items like eggs/meat, but OK. Nice handicap facility room, can park close to make move in/out easy. TV selections are good, helpful staff.
Not many extras, towels are small, bed could use more pillows, not all rooms have microwave and fridge, but they did get them for me. Coffee not as good as some places. Occasionally out of items at breakfast ( milk ). Bagels and E muffins, but no bread
Went above and beyond. Newly refreshed rooms including bathrooms. Spacious!
Clean rooms
Bed and Piilows were rock hard . Did not sleep well
The distance to the boat launch was not bad and the a c worked good
The room seemed dated bedding was old and thin the sink drain did not work had to take the center plunger out to get it to drain and that was nasty and the carpet seemed very stained and dirty this room was not worth 175.00
Good-Clean Friendly and waffles and orange juice and good coffee
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Hey everybody,
I've drawn a polar plot and a default gridline with a spacing of 0.5 has been made in my polar plot. My question is how I can change the spacing of the gridline to be 0.1 instead?
Thank you, Lars
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Lazy Staehs Bed and Breakfast
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All the latest on the world's youngest royals
For Zara Phillips, 2012 is going to be a big year. Not only is she hoping for gold in the equestrian section of the Olympics, but her hideaway Portuguese villa will also finally be ready for her to move into.
In this week's HELLO! magazine, issue 1113, there's an exclusive interview with the Queen's granddaughter about how work is progressing on the holiday home, which she will share with boyfriend Mike Tindall.
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All the latest on the world's youngest royals