text:
Sponsored By
5 Books To Give Dad For Father's Day GiftsDads can be tough to shop for. But don't let the pressure of finding the perfect Father's Day gift fill you with dread. Whether he's into baseball, history or humor, our sister company Simon & Schuster has a book that your dad will love.
Cook Up Dad's Favorite Dishes For The Perfect Father's Day MealA food-filled Father's Day celebration is the perfect way to honor Dad this year.
Mother's Day Gifts For Techy MomsIf your mom loves techy things, chances are she already has that iPad. Here are five other techy gift ideas for your Mom this Mother's Day.
Playing Cupid From The HeartI do think you can play cupid on the cheap this Valentine's Day and still make it special.
The KISS PrincipleI thought it was time again to do a week on being a cheap cupid. Certainly more fun than tax preparation.
Christmas DayMerry Christmas! And of course, I'd like to wish everyone a healthy and wealthy New Year.
Last Minute Gift IdeasThe pressure is mounting. There always seems to be so much to do this week.
The Rules Of RegiftingRegifting is a sophisticated term for something that has been going on since people have been giving gifts.
Holiday Gifting When Money Is TightChristmas can happen even on a tight budget.
Can You Save During The Holidays?Sure! Giving to fewer recipients is a good start.
8 Awful Parting Gifts That Teams Gave Derek JeterFarewell Jeets, here's some future yard sale items!
Your Savings PlanMany people equate saving with some sort of deprivation. If you deprive yourself of all of the fun stuff in life you will never stick to a savings plan.


text:
Research Article
Increased Attentional Control for Emotional Distractors Moderates the Use of Reflective Pondering in Times of Life Stress: A Prospective Study
Article first published online: 3 OCT 2011
DOI: 10.1002/per.846
Copyright © 2011 John Wiley & Sons, Ltd.
European Journal of Personality
Volume 26, Issue 5, pages 474–483, September/October 2012
Additional Information
How to Cite
Vanderhasselt, M.-A., Koster, E. H. W., Goubert, L. and Raedt, R. D. (2012), Increased Attentional Control for Emotional Distractors Moderates the Use of Reflective Pondering in Times of Life Stress: A Prospective Study. Eur. J. Pers., 26: 474–483. doi: 10.1002/per.846
Publication History
- Issue published online: 18 SEP 2012
- Article first published online: 3 OCT 2011
- Manuscript Accepted: 31 AUG 2011
- Manuscript Revised: 28 AUG 2011
- Manuscript Received: 13 MAY 2011
- Abstract
- Article
- References
- Cited By
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subset: commoncrawl


text:
LISTEN TO 710 ESPN Seattle: Mariners vs. Athletics (live stream available in Seattle-Tacoma area only) »
< 710 ESPN Seattle
Sounders vs. Rapids | April 26, 2014
2 of 14
Seattle Sounders' Osvaldo Alonso, right is fouled by Colorado Rapids' Thomas Piermayr, left, Saturday, April 26, 2014, in the first half of an MLS soccer match in Seattle. Piermayr was given a yellow card on the play. (AP Photo/Ted S. Warren)
Photo by MLS Rapids Sounders Soccer - Ted S. Warren
Photo by MLS Rapids Sounders Soccer - Ted S. Warren
2 of 14


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Definitions for labiatifloral
This page provides all possible meanings and translations of the word labiatifloral
Webster Dictionary
alt. of Labiatifloral
having labiate flowers, as the snapdragon
Origin: [Labiate + L. flos, floris, flower.]
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text:
HOLBA Barn in Sennen
from £1 /night help Price for guests, Nights approx:
from £1 /night help Price for guests, Nights approx:
Estimated nightly price based on a weekly stay. Contact the advertiser to confirm the total cost.
Barn / 4 bedrooms / sleeps 7 Home 196429
Availability Your dates are available
Barn / 4 bedrooms / sleeps 7
|Key Info
Set 0.25 miles down a gravelled lane, these lovely Grade II listed barns have been lovingly converted to a good standard. The properties have panoramic countryside views to the rear and are ideal for those who wish to get away from it all to explore this enchanting and rugged area of Cornwall.
Situated in one of Cornwall's most popular areas, you will be a short drive away from a wealth of popular beaches, such as Sennen and Porthcurno and attractions which include Lands End, Flambards Theme Park, Tate Gallery at St Ives and the open air Minack Theatre. Set within a tranquil conservation site, guests are welcome to explore the woodland, wetland and heathland, with its abundant wildlife. Alternatively, simply relax in the large garden with a glass of wine watching the world go by.
Farm activities: the owners have goats, pigs, hens, ducks and ponies which guests are welcome to handle and help with the feeding run. Amenities: bed linen, towels, electric and central heating included. Regret no smoking. Location: beach 4 miles, pub, Post Office and shop 1 mile. Arrival: 3pm.
The accommodation retains many original features such as exposed beams and natural floors, and offers FOUR bedrooms: situated upstairs, 1 double with en-suite shower over bath and WC. Situated downstairs, 1 double, 1 twin (with access to the garden) and 1 single. Bathroom: downstairs with bath, shower over bath and WC. Lounge: located upstairs with flatscreen TV, DVD and woodburner (first basket logs provided). Kitchen/diner: with cooker, microwave, fridge, freezer, washer/dryer, dishwasher and hi-fi. Outside: large enclosed, but not secure, garden with seating, orchard with picnic table within Neolithic enclosure. Amenities: ample parking. 3 well-behaved, medium-sized dogs welcome (more by arrangement). £30 heating surcharge during October - March (inc) payable to owner on arrival.
|Sleeps up to 7, 4 bedrooms
|Nearest beach
|Within 5 miles
|Car advised
|Family friendly
|Great for children of all ages
|Pets welcome, No smoking at this property
Features and Facilities
|Log fire
|4 bedrooms, 2 bathrooms of which 2 Family bathrooms
|Cots (1)
|Linen provided, High chair
|Private garden
|Not suitable for wheelchair users
|Further details indoors
Downstairs Bathroom
|Further details outdoors
Pub Within 1 Mile
Shop Within 1 Mile
Beach Within 5 Miles
The Cornwall region
Contact the advertiser for further information about the region.
Contact the advertiser for further details about the local area of this property.
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This advert is created and maintained by the advertiser; we can only publish adverts in good faith as we don't own, manage or inspect any of the properties. We advise you to familiarise yourself with our terms of use.
You're booking with
The Reservations Team (Property Manager Holiday Cottages)
- 3 Years listed
100% Response rate
Calendar last updated:07 Oct 2015
Based in United Kingdom
- English
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Aug 11, 2011 | 08:44 AM CDT
IFF Posts Q2 2011 Financial Report
Though overall revenue increased 7% over last year's second quarter, the company's fragrance division was challenged with volume declines and raw material price increases.
Aug 10, 2011 | 03:37 PM CDT
Breakout Brand—Sunbow Sunscreen
By: Mary J. Palmieri
HBA blogger Palmieri feels the fun of summer with a new kid-targeted line of sunscreen products.
Aug 04, 2011 | 01:32 PM CDT
U.S. Demand for Cosmeceuticals to Reach $8.5 Billion in 2015
The Freedonia Group reports the segment continues to expand beyond the traditional 45-and-older demographic; antioxidants will remain the largest category, with above-average gains promoted by their incorporation into both topical and ingestible formulations.
Aug 03, 2011 | 04:22 PM CDT
When It's Ready, It's Perfect: a New Fine Fragrance Market Reality
By: Jeb Gleason-Allured, Editor, Perfumer & Flavor…
Speakers from Chanel and Estée Lauder relayed information on building a lasting fragrance at the CEW's Time-Defying Scents panel.
Jul 29, 2011 | 09:29 AM CDT
NPD Group Sees Several Double-digit Increases in Prestige Beauty Sales
January through May 2011 has seen a 9% increase in prestige makeup sales in U.S. department stores, up to $1.4 billion.
Jul 26, 2011 | 10:28 AM CDT
Inter Parfums Post Q2 2011
Company posts a 12.3% increase over the second quarter of 2010; sales in local currency up 19% in South America, 16% in Eastern Europe and 14% in Asia.
Jul 25, 2011 | 01:11 PM CDT
Fashion Fair Cosmetics Names New President
Clarisa Wilson has taken the position of president with Fashion Fair Cosmetics, a division of Johnson Publishing Company.
Jul 13, 2011 | 09:42 AM CDT
From Inspiration to Innovation
By: Lisa Doyle
Experts reveal what makes a new ingredient "one to watch" in skin care.
Jul 13, 2011 | 09:29 AM CDT
The New Alchemy of Multitasking Makeup
By: Emily Katz
Combining skin care with cosmetics appeals to consumers who are seeking economy and efficiency.
Jul 13, 2011 | 08:49 AM CDT
Brazil Breathes New Life Into Global Bath and Body Care
By: Rob Walker, Euromonitor International
Fundamental revitalization of Brazilian domestic demand for bath and body products, Brazil is on course to dethrone the U.S. as the biggest bath and body care market in the world by 2013.


text:
I need an urgent help about compressing an array of integers using zlib,and that will be in c language. i have: uint16_t arrayOfData[120] and i want to compress it so that i get the compressed version and use it in the same program (i don't want to read from and write to streams). please i am waiting for any help, if sample code is available it will be great!
Thanks in advance


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Rawlings Glove Break-In Kit
Product Information:
You're ready for the big game...is your glove? The Rawlings® Glove Break-In kit includes an oversized ball, Glovolium Break-In formula, special compression strap and a Hydra applicator sponge to make sure your glove is in game-ready condition. Complete instructions accompany the kit, so you can field and catch and field with confidence.
- Custom clamshell measures 9" x 11"
- Colorful printed insert card
- Special compression strap
- Oversized ball
- Glovolium Break-In formula
- Durable Hydra applicator sponge
- Great for baseball and softball players alike
- Complete instructions included
- Model: BRKIT
- Rawlings
Country of Origin: ChinaWeb ID: 3879799
Customer Reviews:
Rated 4.2 out of 5�by 77 reviewers.
Rated 5 out of 5�by Tiff Ball supplies The stuff worked good and help break the glove in fast August 4, 2015
Rated 5 out of 5�by Jamoca Great kit!! This kit does it's job! It really helps to break in new gloves! July 14, 2015
Rated 5 out of 5�by Gabey My son loves it. It was easy to break in and he love his new glove! July 14, 2015
Rated 4 out of 5�by KD Rawlings Glove Break-in KIt Everything we needed to do the job of preparing to break-in a new glove was included in the Rawlings Gove Break-in Kit. I liked the idea of using an oversized, plastic ball as the object to mold the pocket of the glove around and the sponge applicator was also a good thing to have. Overall a good product that was well thought out. June 30, 2015
Rated 5 out of 5�by Happyshopper1245 Glove prep Produce was just as explained. Very happy that we purchased this item. June 30, 2015
Rated 3 out of 5�by Mob Ok product It took me multiple layers to get the glove even moving. I really like the strap that it came with. June 23, 2015
Rated 5 out of 5�by Fatmantr Works great Works great on breaking in a new glove and to keep it's shape. June 9, 2015
Rated 5 out of 5�by Justin Great for the glove! I bought I Rawlings Bryce Harper outfielders glove and I bought this to help me break my glove in. After just one use my glove was getting a great pocket and I've used it again to help break it in further. I'm also glad I have this to keep my glove on great condition over time. Highly recommended. June 2, 2015
Rated 5 out of 5�by chilly it works Works well just take little time and practice with it June 2, 2015
Rated 5 out of 5�by Jason63 I love the oversized ball and extra large elastic. Great product. The over sized ball and elastic are a great combination. It helps in defining the character and the personalization of the glove. The easy to use oil and applicator is a bonus! !!!! June 2, 2015


text:
Who We Are
L-3 National Security Solutions (L-3 NSS) is a prime mission partner to defense, intelligence and government agencies, as well as international and commercial organizations. Our integrated solutions combine best-of-breed technology and proven processes with in-field expertise that crosses the domains of cyber, intelligence, enterprise and mission IT, command and control, Big Data and physical security. We partner with customers, industry and academia to develop game-changing innovations that reduce costs and improve performance at the "speed of need."
The Power of Partnership - from Vision to Reality
Lasting Results See how we've partnered with our customers.
September 29, 2015
L-3 Data Tactics Announces Big Data Storage and Analytics Solution for Law Enforcement Body Camera Footage
September 14, 2015
L-3 NSS Awarded Multimillion Dollar DIA Task Order
June 10, 2015
L-3 NSS Receives PVAMU Partner of the Year Award
May 20, 2015
L-3 NSS Names Small Business of the Year Awardees
October 12 – October 14, 2015
AUSA Annual Meeting
November 1 – November 4, 2015
AATCA Annual Conference & Expo
November 16 – November 19, 2015
AFCEA Alamo ACE Conference & Expo


text: Booked through Lastminute.com we stayed at this basic hotel, located just outside the business district of Paris. Staff were welcoming and friendly. Despite emailing in advance asking for room with view of Paris, we were given one without. It was clean, good size for the price, and had a decent bath and shower. Walls were thin, and couple next door... More


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People tend to check in during these times:
Add hours
The Moore Warren Theatre has 14 luxurious auditoriumsand is the first theatre to incorporate all Digital Cinema and THX technology! Balcony and Lounge The Warren Diner Spacious Game Room IMAX Coming Soon!!!!!
Probably the best theater in the metro area. Full service bar, with a separate building for 3D and special effect movie features.
This is the only theater that I will go to. The director suite and the balcony has spoiled me.
Best movie experience in OKC area!
The best theater in Oklahoma.
Balcony is a good experience.
The balcony is fun.
The #imax theatre was amazing, playing an amazing movie ... #americansniper! A must see if you haven't. #negativereviewsmyass #hooah
Beautiful, old school theater. Just get there early for a good seat.
With my two favorite guys Berton & Jeremy seeing Mockingjay Director's Suite at the Warren. Yep! Recliners, heated seats, full bar and restaurant.
Balcony! It has heated seats and wait staff at the press of a button.
The director seats are really the best in the house. Order online and pick up at a kiosk to avoid the crowds.
Balcony seating is worth the additional $$! Great service.
The directors suites
Seeing Guardians Of The Galaxy IMAX 3D. It sucks you can't check in anymore. Not getting "Swarm"
Directors Suite is totally worth it!
Fantastic. What a blessing for those who survived the storm. Many came to know Christ.
Tickets to Where Was God? Stories of Hope After the Storm on sale now. Opens May 16. #WhereWasGod
a friendly theater, great staff, and equipped with cry rooms!
Directors suite is awesome. ..great date night
Give them crap about the grammatical error on their sign@leading upstairs: "Please have your id's ready"
Pay the extra money for balcony. No kids and butt warmers. The bar is good too.
Great theater.
Really really good movie
Great IMAX theater
The Directors suite is like dinner drinks and a movie all in one
Balcony seats at the Warren are the best seats in town!
Directors seating is the best!
Director's Suite cannot be beat! Excellent experience!
Awesome theater.....
My favorite theater in Oklahoma
Make sure to visit the diner, best tea EVER!!! Great service too
So gross!! Ppl taking their shoes off and putting their bare feet all over the DIRECTORS SUITE chairs. + Everyone talks During the movie
Love the idea of being able to purchase tickets online. Get to imax early so you can sit in the center.
Go to the IMAX or go home. That IMAX is so nice that you will never want to waste your time in another theater again.
Best theatre I've ever been to! The grilled chkn salad at the little restraunt was great too :)
Even in the middle of all the tornado damage, The Warren is a great place to watch a movie.
The Director's suite is Awesome! !!.
The Director's Suite is pricey, but worth every cent! Luxury chairs-reclining & heated with personal cup holder and food tray, fantastic wait staff, designated seats you choose, and a private lounge!
IMAX is fantastic! Try to get there early so you can get a good seat.
Really only good for the balcony, but still worth the trip every time even if balcony is sold out
The desserts aren't half bad-try a root beer float at the bar upstairs! It comes in a gargantuan mug. Delicious!
The Social Media Staff here sends prayers to those affected by the horrible Tornado in Oklahoma. Read more
The top row of the IMAX theater has a smaller bathroom in the foyer at the back. Climb fewer stairs and escape back to the movie quicker!
Make your plans early in the week if you want good balcony or director's suite seats. Get them online!
I love the Warren
You're at the Warren. Be sure to stop by Fort Thunder Harley-Davidson next door. Hundreds of new & used motorcycles & the coolest Harley motorclothes. Need a new Harley? Ask for Jason or Mike.
Top Gun was AMAZING again, every time I see it!
the directors suite is the best way to watch a movie!
Balcony seats are the shit!!!!
Where did all these people come from? I had to park by I-35. Not about to stand in line for a coke. This is crazy.


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Nestled in the mountains on the north shore of beautiful Lake Tahoe, the Big Water Grille offers spectacular panoramic lake views, both inside and out. Our California bistro menu has been updated with a welcome Southern twist. We feature an extensive wine list from around the world, as well as a full bar with signature martinis, cocktails and craft beers.
Come to Lake Tahoe's premier fine-dining restaurant—where both the view and the food will take your breath away.
Explore our exquisite menus
including our famous Ahi Tuna Poke, Braised Pork Belly
Salads, Steaks, Fresh Seafood, House Made Desserts and more.
Click here to see our menus.
341 Ski Way
Incline Village, NV 89451
Lake Tahoe
click for turn by turn directions
click to view directions on google maps from your current location
Click to Email
click to get directions on your phone
Bar ~ 4.30pm
Dining Room ~ 5.30pm
Big Water Grille, est. 1998 – 775.833.0606


text:
Reviews and ratings of local lawyers.
Post a review of your attorney.
Learn when to hire and how to choose the right attorney.
Browse articles and Q&A on different legal topics.
For $39 talk directly to a top-reviewed lawyer on the phone using Avvo Advisor. Get your questions answered in a 15-minute call. Advisor is also available as a mobile app.
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Avvo Rating: 10.0
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We represent small companies, startups, and business people, helping you to solve legal problems
Practice areas & skills: Copyright Infringement, Litigation, Business, Entertainment, Trademark Infringement
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Attorney Albert Cohen is the founder and owner of Cohen & Cohen Law Group, P.C., conveniently located in Forest Hills, New York. Mr. Cohen has a busy and successful practice with focus on; estate planning and elder law, personal injury, and immig...
Practice areas & skills: Personal Injury, Elder Law, Estate Planning, Probate
Licensed since 1992
I bring more than 20 years of experience in mediation and litigation in New York courts to help people reduce costs and resolve conflicts with dignity. People going through a divorce, separation or another legal process are often surprised by the ...
Practice areas & skills: Family, Mediation, General Practice
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24/7 Top Criminal / DUI DWI lawyer who has successfully handled over 2000 cases in most NY counties.
Practice areas & skills: Criminal Defense, DUI & DWI
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Elder Law, Trusts & Estates, Medicaid Eligibility, Special Needs Planning, Guardianships, Probate
Practice areas & skills: Aged and Aging, Estate Planning, Insurance, Real Estate
5.0 stars 13 reviews
Licensed since 2007
Zachary Reibstein began his career in 2002 as a paralegal with the Queens County District Attorney's Office. In this position he interviewed crime victims, witnesses and officers to help decide what charges (if any) were to be brought. In late 200...
Practice areas & skills: Criminal Defense, DUI & DWI, Personal Injury, Civil Rights
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Licensed since 1978
Practice areas & skills: Social Security
Licensed since 2008
Attorney Raisa Cohen, is a partner with the Cohen & Cohen Law Group, P.C.
Mrs. Cohen works closely with people from all over the world and help them build their lives in the United States, whether they desire to reunite with their families, or t...
Practice areas & skills: Immigration, Estate Planning
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Client Focused. Results Driven. Former Prosecutor.
Practice areas & skills: Criminal Defense, Immigration, Wills & Living Wills, Real Estate
5.0 stars 3 reviews
Avvo Rating: 8.5
Our NY estate lawyers at this firm have been helping families in New York plan and administer their estates for years. With more than 40 combined years of legal experience probating and challenging wills, setting up elaborate trusts and family l...
Practice areas & skills: Estate Planning, Real Estate


text:
Main Page
From URCFwiki
Proteus is part of the University Research Computing Facility.
Proteus Status
- 2015-10-08:
- Python 3.5.0 is now available
- 2015-10-05:
- Corrected Job Script Example 02 Many Input Files -- index off by one error. Added second example where input files are named sequentially, but no separate file containing the filenames is available.
- 2015-10-01:
- Math rendering (use LaTeX as markup) now works, e.g. Right-click on rendered math for options.
- 2015-08-31:
- New article: Compiling Vowpal Wabbit (machine learning software)
- 2015-08-28:
- New article: Compiling GAML (bioinformatics software)
- 2015-08-19:
- System-provided Octave 3.4.3 has been removed. In its place, Octave 4.0.0 has been installed. Use modulefile "octave/current"
- 2015-08-11:
- Ray, VSEARCH, and PyRAD bioinformatics software installed. Example job scripts: Job Script Example 04 Ray assembler, Job Script Example 05 pyRAD
- 2015-08-06:
- Big Data Genomics' ADAM 0.17.0 has been installed. Please see the ADAM article for details.
- 2015-08-04:
- Apache Spark 1.4.1 has been installed. Please see Apache Spark article for details.
- Interactive GUI applications may be run on compute nodes. Please see: Introduction to Using Proteus#Interactive Sessions
- 2015-07-24:
- Article on OpenMPI updated with new recommendation. mpirun should be run with the full path to the executable. This is provided by the MPI_RUN environment variable.
- 2015-07-17:
- New article added: Lustre Scratch Filesystem
- 2015-06-30:
- Leap second has been added with no adverse effects
- 2015-06-26:
- Matlab R2015a has been installed
- 2015-06-23:
- New article: Tips for Mac OS X Users
- 2015-06-02:
- New module for Intel Composer XE 2013 will pull in all components: intel/composerxe/2013.3.174 See article on Intel Compilers
- DIAMOND bioinformatics software has been installed, with instructions for compiling
- Some BLAST Databases have been installed with system-wide read-only access
- Samtools article created
- Bowtie article created
- Lighter has been installed
- 2015-06-01:
- PICRUSt 1.0.0dev0 has been installed
- Updated instructions on installing Python modules
- 2015-05-29:
- QIIME 1.9.1 has been installed
- Installing Software for Your Research Group article has been updated
- 2015-05-20:
- Issue with running namd/intel/2015/openmpi/2.10 resolved. See Compiling NAMD#Locally-compiled version using Intel MKL
- Issue with MATLAB 2014b toolbox licenses resolved
- 2015-05-07:
- MATLAB GUI again usable from login nodes; to enable this, memory limit on user processes has been removed - computations requiring large amounts of memory must be submitted as cluster jobs
- Compiling VASP article updated
- 2015-05-05:
- Global h_rt limit will be reduced to 48 hours this week
- Instructions on requesting an interactive session on a compute node added: Introduction to Using Proteus#Interactive Sessions
Known Issues
- Password change after expiration is broken. See Introduction to Using_Proteus#Changing Passwords. Please email urcf-support for a manual reset.
- 4 AMD nodes are offline
URCF Proteus Documentation Wiki
You can login here with your Proteus account: select drexel_urcf in the dropdown menu on the login page. Please feel free to create and edit articles if you wish.
Documentation is being created as we go along. Please see the Recent Changes page for updates.
System Information and Policies
- Proteus web portal, showing current cluster status including job queue. The qstat command provides more information.
- Facility Description for Proposals
- Proteus Hardware and Software
- Terms of Use
- Job Scheduling Algorithm
- Benchmarks
Getting Started
- Introduction to Using Proteus
- Recommendations for Jobs
- Miscellaneous Tips
- Installing Software for Your Research Group
- Articles here are collected into Special:Categories
See also all the articles in the Category:Quick Start Guides
Other Online Documentation
Getting Help
Please contact URCF support via the issue tracking system:
This ensures a record is kept of your request and all work done for it.
See also: Frequently Encountered Problems
Useful Links
- Proteus Web User Portal -- login with your Proteus account
- Proteus load monitoring
- List of all articles in this wiki
- List of files available (PDFs of documentation, etc.)


text:
Return to SwingLifeStyle.com The Swingers Home Page
There are a total of 10433 Graham swingers, within 100 miles.
The list below is a subset of the swingers in the Graham area.
Create a free swingers account so you can see and write to them all.
If you do not at least open a IM request how do you know what was said.
Share the Love
Let's Marvin Gaye and get it on!
mwc looking for female 3rd
Ready,wild&willing anything
I'm ready for fun
wanting to play
life is short, play hard
Still looking to explore with fun people
Looking for some sexy time
We would love to try this out
Moving to Wedowee in mid July!!! Hit us up!!!
Waiting on that bird to fly
horny all the time
Still looking for that fun compatible and attractive duo!
hot couple looking
Sex and more sex
Going to the Grove Sunday, October 11
Dance if you dare!!
Active Swingers as of 13-Oct-15.
This site does not contain sexually explicit images as defined in 18 U.S.C. 2256.
Accordingly, neither this site nor the contents contained herein are covered by the record-keeping provisions of 18 USC 2257(a)-(c).
Disclaimer: This website contains adult material. You must be over 18 to enter or 21 were applicable by law.
All Members are over 18 years of age.
Terms of Use Privacy Policy


text:
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Washington, D.C. native Chef Barton Seaver began his professional career working for popular D.C. restaurants such as Ardeo, Felix and Greenwood. After years of invaluable kitchen experience, Seaver made his way to Hyde Park, New York, where he trained at the renowned Culinary Institute of America. Upon graduating with honors, he immediately took a fellowship position at C.I.A. as a graduate teacher in both the meat and fish classes. Working in this hands-on environment taught Seaver the importance of proper handling and techniques of exceptionally fresh products, all the while giving him direct access to sources of fish through the eastern seaboard ports.After his tenure at the C.I.A., Seaver's classical training led him to Europe and traveling extensively throughout the Iberian Peninsula and Africa where he participated in old world traditions of farming and harvesting from the sea. Recently awarded two and a half stars by Washington Post food critic Tom Sietsema, Hook allows Chef Seaver's dedication to the use of sustainable seafood to flourish. As one of the cause's biggest advocates, Chef Seaver looks to his restaurant to serve as an educational arm and influence in the commmunity as a 100% sustainable, fish focused restaurant. The most sought after item on the menu are the fresh crudos. Seaver is also a certified sommelier through the Sommelier Society of America and is continuing studies with Wine and Spirits Educational Trust in London. Additionally, he is also active in the Slow Food movement, and recently cooked at the bi-annual Slow Food Terra Madre conference in Italy.
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Blood Brothers features 13 one-night scenarios, all based on familiar themes typical of the kind found in B-movies. Explore the land that time ignored, escape from a town infested with the living dead, spend the weekend in a haunted house, fight the mummy, meet an animated scarecrow, track down a vengeful villain, and tangle with Nazi shamans. A light-hearted break from the grim world of the Cthulhu Mythos.
More editions of Blood Brothers: 13 Tales of Terror (Call of Cthulhu):
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Bloomberg TV+
By Bloomberg Finance LP
Open iTunes to buy and download apps.
- Mobile Excellence Award for Best Mobile Utility Application
- App Gem Award from Macworld
Bloomberg Television is a 24 hour global business & financial news network that is watched by the most affluent and influential viewers in the world. It is supported by the world's largest international news bureau network with 146 bureaus in 72 countries.
With Bloomberg TV+ Watch:
- Live TV: Bloomberg Television Live 24-hours a day
- The biggest business, finance and technology stories right now
- Featured videos and breaking news stories directly from the homepage
- The most watched videos from the last 24 Hours and last 7 days across mobile and Bloomberg.com
- All the 'New' episodes added within channels since your last login, now tagged for easier discoverability
- Exclusive interviews with the most influential people in business, finance and technology
- Bloomberg's critically acclaimed shows on demand
- Download videos for offline viewing
- Get extra content on people, companies and topics while watching
- Search our extensive library of video content
- Add up to 10 personal channels for companies, people or topics and access them by adding them to the homepage's 'My Channels' section
- Play audio in the background while browsing other apps
- Activate subtitles for full episodes in channels
- Set and receive reminders for upcoming programs on Live TV as well as notification when new videos are added to your favorite On Demand channels
- Synchronize your playlist with Bloomberg.com
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Shows available on demand include:
- Bloomberg West
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Please send any feedback from within the app by going to the info section.
What's New in Version 1.4.7
- Fixes iOS 8.4 compatibility issues
iPad Screenshots
Customer Reviews
Appreciate it!
I love this app and use it often. Some of the liberal bias during the day is troubling but it is a free channel. I like the interviews with the CEO's and heads of companies on the week ends especially. Suggestion: when you put up a stock and talk about it pleeeeease put the ticker up there too.
A great financial channel for free!
I've watched Bloomberg TV for several years via the iPad and the quality of the programming has steadily improved while the app has remained excellent. Enough said.
Good Overall
The video feed pauses from time to time while the audio continues to play. That's about my only complaint.
- Free
- Category: News
- Updated: Jul 21, 2015
- Version: 1.4.7
- Size: 30.7 MB
- Language: English
- Seller: Bloomberg Finance LP
- © 2014
Compatibility: Requires iOS 6.0 or later. Compatible with iPad.


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Is this restaurant family-friendly?
Is this restaurant good for breakfast?
Is this restaurant good for couples?
Is this restaurant good for business?
Does this restaurant serve Mexican food?
Is this restaurant good for lunch?
Is this restaurant good for dinner?
Is this restaurant good for brunch?
Does this restaurant offer takeout or food to go?
Does this restaurant offer free wifi?
Thanks for helping!
Food was good and authentic. Service is poor and i dont believe it was just our server. it seems to be a common thing among the staff. The owner might want to look into re-energizing their employees or finding new ones
Really disappointed. The restaurant came highly recommended by a family member but it most certainly did not live up to the recommendation. My food was over cooked. There are no wait staff. You get your own refills. The cashier was lethargic and ever so slightly confrontational. Despite the discount environment my food was most certainly not discounted. My wife really...
Passing through Del Rio we found Don Marcelino's. I was recommended to us by a state trooper. We were glad we found this restaurant. The tortillas were very fresh and the rice and beans were very good. I ordered the T-bone steak and it was cooked just like i requested and the taste was excellent. They didn't have a wait...
Being smack dab on the U.S. MEXICAN border I would think there are mexican food restarunts on every corner. Not the case. Don marcellinos is more of a fast food place than a sit down and order sorta place. My food was poorly plated. Tacos crumbled apart. Waiters waitresses don't exist. You order at counter, given a number and told...
With the Mexican border in view you would expect great food and you won't be disappointed. The selection is excellent and the service very good.
I hate having to order at the counter and have to pay for chips and salsa, which are not all that great, however the food is pretty good. They serve really good caldo de res. Not your typical Tex-Mex Restaurant. Nice decor inside.
I expected good Mexican food to be a given in Del Rio, Texas so the challenge was to find the BEST in the city. Many locals recommended Don Marcelino's - must be the local joke. The 3 of us live in San Antonio and are no strangers to a good enchilada. However here, the atmosphere was fine, even had a...
I have been to this restaurant before and nothing have really changed the food average the service average prices average
Lots of people love this place but I'm just not a fan. It's cheap enough but not great quality food.
Have eaten here twice but have not been impressed. Will look for a better Mexican restaurant because this one does at best will be average or below.
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Metallica - Page 15
No New Metallica Until 2015?
Metallica Announce 'Through the Never' Movie Release Dates
As Metallica continue to put the finishing touches on their upcoming film 'Metallica Through the Never,' some exciting new details have been revealed. With a debut date of Sept. 27, the movie will have a banner premiere week taking over every IMAX theater from coast to coast with exclusive screenings of the monster 3D film.
The Future of Rock is a 10-Year Old Girl
Metallica 'Hoping' To Get Album Out in 2014
Stern Announces Their Next Pinball is a Master of Puppets
Metallica Adds To Orion
Duff McKagan, Lars Ulrich + More Appear in Alice In Chains Promotional Video
One of the knocks on the grunge scene of the 1990s was that its musicians took themselves way too seriously. However, Seattle's Alice in Chains, one of the defining bands of the genre, are looking to refute that charge thanks to a new video promoting their upcoming release, 'The Devil Put Dinosaurs Here,' which features a handful of classic rockers appearing as themselves.
Metallica's Manager Thinks Justin Bieber Deserves A Spanking
In his years as a rock n' roll manager, Peter Mensch has certainly seen more than his share of childish behavior. Now, Mensch, who manages such big names as Metallica and Red Hot Chili Peppers, wants to bring his expertise to help put formerly squeaky-clean pop star Justin Bieber in his proper place.


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Best of Entertainment
A film poster advertising Bangladeshi film 'Most Welcome 2' hangs in... News PhotoAdvertisement,Arts Culture and Entertainment,Bangladesh,Dhaka,Film Industry,Film Poster,Hanging,Horizontal,Movie,Poster,Shopping,Shopping MallPhotographer MUNIR UZ ZAMANCollection: AFP A film poster advertising Bangladeshi film 'Most Welcome 2' hangs in front of a cinema hall at a shopping mall in Dhaka on September 3, 2014. Authorities in Bangladesh have banned local film-makers from giving their movies English titles after a spate of recent Bangla blockbusters with titles such as 'Honeymoon' and 'I Don't Care'. Mushfiqur Rahman Gulzar, general secretary of the Bangladesh Film Directors' Association, said the government had instructed the industry to ensure that all future homegrown releases have Bangla names. AFP PHOTO/Munir uz ZAMAN (Photo credit should read MUNIR UZ ZAMAN/AFP/Getty Images)


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This is a discussion on If you could be a tooth fairy for a day within the ISTJ Forum - The Duty Fulfillers forums, part of the SJ's Temperament Forum- The Overseers category; Originally Posted by Sela If it ain't broke, don't fix it. ;) He's actually a member of MENSA, but working ...
People/sheeple need to get with the program and realize that people that have a high social standing/rich/educated aren't automatically intelligent, just as people that don't have a high social standing aren't automatically stupid.
Carry on.
While I was delivering pizzas to put myself through school, a man actually told his young daughter: "Be sure to get a good education or you will end up delivering pizzas like her". I just smiled and thanked him for his patronage.
Just like I'll smile and take care of his rude ass if he shows up as my patient one day....
Sorry, Sela's rant reminded me of that. It is both funny and horrifying at how rude and judgmental people can be sometimes (and he is teaching this behavior to his daughter by example, nice).
Hahaha @Ryan . Perhaps his logic has been poisoned.
On topic:
I would make a terrible tooth fairy. Collecting teeth = creepy. I mean really. What use could a bunch of kids' teeth have and why on earth would I pay good money for them?
Now sh*ting rainbows, that's useful stuff!
That tooth rat is just a tooth fairy usurper. Bad tooth rat.
ENFP tooth fairy? Well obviously there'd be lots of tantalizing tea-parties where we'd brainstorm better ways to do the whole tooth-fairy thing and of course I'd have a magic wand wouldn't I? Mmmm and I really don't like rats at all.
*asks in a stern voice with arms crossed and 1 tapping leg*
Okay, what's happenned to the ISTJs lately? Has someone been fiddling around with their robotic programming....again?
It seems we currently are experiencing a number of random issues with the forum. These could include: ghost private messages, incorrectly dated PMs, old PMs becoming unread, phantom notifications, deleted accounts, etc.Bear with us while we figure out what is going on. If you have any issue to report, please do so in the support forum. Don\'t panic!


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The Times Union printed an A1 story by Cathleen Crowley on this issue on Sunday, April 27:
Empty land, full rage over new tax values from Bethlehem landowners: Longtime Bethlehem landowners warn new tax rates will force sales, changing town
Here is a previously written story from Cathleen Crowley:
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BETHLEHEM — About 50 angry landowners gathered at the Town Board meeting on Wednesday night to confront town leaders about the soaring assessments on the vacant land they own.
Almost every parcel of open land in Bethlehem, particularly large tracts in South Bethlehem, Selkirk, and Glenmont, saw its assessment increase by more than 25 percent and in many cases more than 100 percent. Families affected by the increase say they will log and sell their land to developers, forever altering the character of Bethlehem's rural hamlets.
One after another, they vacant landowners spoke for nearly two hours during the public comment period, and walked out en masse when Town Supervisor John Clarkson defended the assessment. The town's position is that the properties in question — many belonging to the farm families that were early settlers in the town — have been undervalued and undertaxed for years.
A Grievance Day will take place on May 27 for landowners who want to appeal their assessments. The assessments are considered preliminary until the final rolls are adopted in July.
Whose side are you on, the landowners or Town Hall? Make your case in the comments.


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Sounds Like: Incubus, Linkin Park, Daft Punk, John Mayer, Karnivool
Label: Independent
Manager: Jonathan Brown
Bio: I picked up my first instrument, the guitar, the day that I turned 12 years old. It didn't take long before I began my instrument collection; I picked up a bass, djembe, didjeridoo, keyboard, drums, ocarina, some various native american flutes, maracas, a ukulele – the list is a little ridiculous...See Full Bio


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Written on: 25/02/2013
I use hotel.de for the last 10 years or so and never found a better, simplier and more comfortable booking platform. I highly appreciate the great service. Thanks!Visit hotel.info
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|Eye of the Tiger
|E7 6c
Rockfax Description
FA. P Williams J Amies 1963 FFA. Ron Fawcett 1982
Ticklists: Trad climbs for sport climbers, Rockfax Peak Limestone Top 50, World Graded List, Peak Rock/15/The Dawn of Sport:A Bolt From the Blue, 100 or so good E6s - aye Caff.
Photo: Eye of the Tiger © Ethan Walker


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|Publication number
|Publication type
|Application number
|Publication date
|15 Feb 2005
|Filing date
|15 Mar 2002
|Priority date
|16 Mar 2001
|Fee status
|Also published as
|Publication number
|Joseph C. Trautman, Cedric T. Wright, Michel J. N. Cormier
|Original Assignee
|Alza Corporation
|Export Citation
|BiBTeX, EndNote, RefMan
|Patent Citations (30), Referenced by (54), Classifications (16), Legal Events (4)
|External Links: USPTO, USPTO Assignment, Espacenet
Priority is claimed under 35 U.S.C. 119(e) from U.S. Provisional Patent Applications Ser. Nos. 60/276,762 filed Mar. 16, 2001; 60/342,550 filed Dec. 20, 2001; and 60/351,586 filed Jan. 22, 2002.
This invention relates to administering and enhancing delivery of an agent into or through the skin. More particularly, the invention relates to a method and apparatus for making a percutaneous drug delivery system for administering therapeutic active agent (i.e., a drug or vaccine) into or through the skin using skin piercing microprojections which have a dry coating of the agent. Delivery of the agent is facilitated when the microprojections pierce the skin of a patient and the patient's body fluid contacts and dissolves the active agent. Even more particularly, the invention relates to a method and apparatus for selectively coating the agent on the microprojections.
Transdermal drug delivery systems generally rely on passive diffusion to administer the drug while active transdermal drug delivery systems rely on an external energy source (e.g., electricity) to deliver the drug. Passive transdermal drug delivery systems are more common. Passive transdermal systems have a drug reservoir containing a high concentration of drug adapted to contact the skin where the drug diffuses through the skin and into the body tissues or bloodstream of a patient. The transdermal drug flux is dependent upon the condition of the skin, the size and physical/chemical properties of the drug molecule, and the concentration gradient across the skin. Because of the low skin permeability to many drugs, transdermal delivery has had limited applications. This low permeability is attributed primarily to the stratum corneum, the outermost skin layer which consists of flat, dead cells filled with keratin fibers (keratinocytes) surrounded by lipid bilayers. The highly-ordered structure of the lipid bilayers confers a relatively impermeable character to the stratum corneum.
One method of increasing the passive transdermal diffusional drug flux involves mechanically penetrating or disrupting the outermost skin layers thereby creating pathways into the skin in order to enhance the amount of agent being transdermally delivered. Early vaccination devices known as scarifiers generally had a plurality of tines or needles which are applied to the skin to and scratch or make small cuts in the area of application. The vaccine was applied either topically on the skin, as disclosed in Rabenau, U.S. Pat. No. 5,487,726 or as a wetted liquid applied to the scarifier tines as disclosed in Galy, U.S. Pat. No. 4,453,926, Chacornac, U.S. Pat. No. 4,109,655, and Kravitz, U.S. Pat. No. 3,136,314 or as a dry coating on and between the scarifier tines as disclosed in Kravitz U.S. Pat. No. 3,351,059. Scarifiers have been suggested for intradermal vaccine delivery in part because only very small amounts of the vaccine need to be delivered into the skin to be effective in immunizing the patient. Further, the amount of vaccine delivered is not particularly critical since an excess amount achieves satisfactory immunization as well as a minimum amount. However a serious disadvantage in using a scarifier to deliver a drug is the difficulty in determining the transdermal drug flux and the resulting dosage delivered. Also due to the elastic, deforming and resilient nature of skin to deflect and resist puncturing, very tiny (e.g., having lengths less than about 0.5 mm) skin piercing elements often do not uniformly penetrate the skin and/or are wiped free of a coating, particularly a liquid coating, of an agent upon skin penetration. Additionally, due to the self healing process of the skin, the punctures or slits made in the skin tend to close up after removal of the piercing elements from the stratum corneum. Thus, the elastic nature of the skin acts to remove active agent coating the tiny piercing elements upon penetration. Furthermore the tiny slits formed by the piercing elements heal quickly after removal of the device, thus, limiting the passage of agent through the passageways created by the piercing elements and in turn limiting the transdermal flux of such devices.
Other devices which use tiny skin piercing elements to enhance transdermal drug delivery are disclosed in European Patent EP 0407063A1, Godshall, et al. U.S. Pat. No. 5,879,326; Ganderton, et al. U.S. Pat. No. 3,814,097; Gross, et al. U.S. Pat. No. 5,279,544; Lee, et al. U.S. Pat. No. 5,250,023; Gerstel, et al. U.S. Pat. No. 3,964,482; Kravitz, et al. U.S. Pat. No. Reissue 25,637 and PCT Publication Nos. WO 96/37155, WO 96/37256, WO 96/17648, WO 97/03718, WO 98/11937, WO 98/00193, WO 97/48440, WO 97/48441, WO 97/48442, WO 98/00193, WO 99/64580, WO 98/28037, WO 98/29298, and WO 98/29365; all incorporated by reference in their entirety. These devices use piercing elements of various shapes and sizes to pierce the outermost layer (i.e., the stratum corneum) of the skin. The piercing elements disclosed in these references generally extend perpendicularly from a thin, flat member, such as a pad or sheet. The piercing elements in some of these devices are extremely small, some having dimensions (i.e., a microprojection length and width) of only about 25-400 μm and a mircorprojection thickness of only about 5-50 μm. These tiny piercing/cutting elements make correspondingly small microslits/microcuts in the stratum corneum for enhanced transdermal agent delivery therethrough.
More recently, Cormier et al., in U.S. patent application Ser. No. 10/045,842 filed Oct. 26, 2001 disclose a device for transdermally delivering a potent drug. The device has a plurality of skin piercing microprojections which have a dry coating of the drug. Cormier et al. disclose microfluidic coating techniques such as ink jet printing to selectively coat the drug only on the skin piercing microprojections rather than on other portions/surfaces of the device which do not penetrate into the skin. In spite of these disclosures, Cormier et al. do not address the difficulties in aiming the microfluidic spray or deposit only onto the portions of the device which pierce the skin. Thus, there is a need for a precisely controlled coating method which can reproducibly, and at high volumes, coat only the skin-piercing portions of such devices.
The apparatus and method of the present invention overcome these difficulties by providing a coating liquid of precisely controlled depth and conveying, in a precisely controlled manner the microprojections through the coating liquid. The method of the present invention is useful for coating a liquid onto a plurality of microprojections extending from a surface or edge of a substrate without coating the liquid onto the substrate itself. The method includes providing an agent-containing coating liquid and conveying the liquid onto a liquid-holding surface having a coating transfer region. The depth of the coating liquid on the coating transfer region is precisely controlled to a predetermined depth. The microprojections are immersed to a predetermined level in the coating liquid at the coating transfer region. The depth of the coating liquid in the coating transfer region should be at least slightly greater than the level of immersion of the microprojections, as measured perpendicularly from the substrate surface or edge. The microprojections are most typically immersed only partially in the coating liquid so that only a portion of the entire length of the microprojections is coated. After coating, the microprojections are removed from the coating liquid and then dried thereby forming a dry agent-containing coating on the microprojections. An important advantage of the present invention is that for very expensive agents (e.g., expensive drugs or vaccines), the agent is coated only on those portions of the device which pierce into the skin, i.e., only the microprojections and not the substrate is coated with the agent.
The apparatus of the present invention is suitable for coating an agent-containing liquid onto a plurality of microprojections extending from a surface or edge of a substrate substantially without coating the substrate. The apparatus includes a liquid holding surface having a coating transfer region. The liquid holding surface can be either curved or flat. A liquid conveyor conveys the coating liquid to the coating transfer region. A coating thickness controller controls the thickness of the coating at the coating transfer region to a precisely predetermined thickness. A positionably adjustable substrate conveyer conveys the microprojections past the coating transfer region such that the microprojections are immersed to a predetermined depth level in the coating liquid.
In one embodiment, the liquid holding surface is the cylindrically-shaped outer surface of a rotatable roller or drum. The coating liquid is conveyed to a coating transfer region by rotating the roller or drum through a bath of the coating liquid. The coating thickness controller can be either a doctor blade and/or a second roller substantially parallel with the liquid conveying roller or drum and spaced a predetermined distance therefrom.
In a second embodiment, the liquid holding surface, either curved or flat, is substantially immobile and the coating liquid flows e.g., by force of gravity, thereover.
The substrate conveyer can take any of several forms. In one embodiment, the substrate conveyer comprises a track which is positionally adjustable relative to the coating transfer region. A substrate holding sled runs along the track past the coating transfer region.
In a second embodiment, the substrate conveyer continuously conveys a web comprised of a plurality of substrates past the coating transfer region. The continuous substrate conveyer can include a substrate web supply roll and a take-up roll with a positionally adjustable web guide therebetween for positioning the continuous web relative to the coating transfer region.
Preferably, the agent is sufficiently potent to be therapeutically effective in a dose of less than about 1 mg, and preferably less than about 0.25 mg, per application. Preferably, the agent has a water solubility of greater than about 50 mg/ml, and more preferably greater than about 100 mg/ml. The liquid coating solution or suspension typically has a viscosity of about 5 to 500 centipoise (cP), more typically about 20 to 50 cP, when measured at a temperature of 25� C. and a shear strain rate of 100 sec−1. The thickness of the solid (i.e., after drying) coating on the microprojections is preferably less than the thickness of the microprojections, more preferably the thickness is less than 25 μm and most preferably less than 10 μm. Generally, the coating thickness is an average thickness measured over the surfaces of the microprojections.
The agent for coating the microprojections is selected to have sufficient potency to be therapeutically effective when administered transdermally in an amount of less than about 1 mg, and preferably less than about 0.25 mg, of active agent. The most preferred agents are vaccines and potent drugs. Preferred potent drugs include ACTH (1-24), calcitonin, desmopressin, LHRH, LHRH analogs, goserelin, leuprolide, PTH, vasopressin, deamino [Val4, D-Arg8] arginine vasopressin, buserelin, triptorelin, interferon alpha, interferon beta, interferon gamma, FSH, EPO, GM-CSF, G-CSF, IL-10, glucagon and analogs of these agents including pharmaceutically acceptable salts thereof.
The invention will now be described in greater detail with reference to the preferred embodiments illustrated in the accompanying drawings and figures wherein:
The term "transdermal" means the delivery of an agent (e.g., a drug or vaccine) into and/or through the skin for local or systemic therapy.
The term "transdermal flux" means the rate of transdermal delivery.
The term "microprojections" refers to piercing elements which are adapted to pierce or cut through the stratum corneum into the underlying epidermis layer, or epidermis and dermis layers, of the skin of a living animal, particularly a human. The piercing elements should not pierce the skin to a depth which causes bleeding. Typically the piercing elements have a blade length of less than 500 μm, and preferably less than 250 μm. The microprojections typically have a width of about 75 to 500 μm and a thickness of about 5 to 50 μm. The microprojections may be formed in different shapes, such as needles, hollow needles, blades, pins, punches, and combinations thereof.
The term "microprojection array" as used herein refers to a plurality of microprojections arranged in an array for piercing the stratum corneum. The microprojection array may be formed by etching or punching a plurality of microprojections from a thin sheet and folding or bending the microprojections out of the plane of the sheet to form a configuration such as that shown in FIG. 1. The microprojection array may also be formed in other known manners, such as by forming one or more strips having microprojections along an edge of each of the strip(s) as disclosed in Zuck, U.S. Pat. No. 6,050,988. The microprojection array may include hollow needles which hold a dry pharmacologically active agent.
The present invention provides an apparatus and method for selectively applying an agent-containing liquid on the skin piercing portions of a microprojection device having a plurality of stratum corneum-piercing microprojections extending therefrom in order to form an agent-containing coating on the microprojections. The liquid-coated microprojections are then dried to form a solid coating thereon which contains the agent. The microprojections are adapted to pierce through the stratum corneum into the underlying epidermis layer, or epidermis and dermis layers, but do not penetrate so deep as to reach the capillary beds and cause significant bleeding. Typically, the microprojections have a length which allows skin penetration to a depth of up to about 500 μm, and preferably up to about 400 μm. Upon piercing the stratum corneum layer of the skin, the agent-containing coating is dissolved by body fluid (intracellular fluids and extracellular fluids such as interstitial fluid, blood, or mixtures thereof) and released into the skin for local or systemic therapy.
In accordance with the present invention, the agent-containing coating is applied after the microprojections 12 are formed (i.e., etched) and bent out of the plane of metal sheet 14. The coating on the microprojections 12 is formed by a dip-coating using the apparatuses shown in
The material used for the drum 22, or any surface treatment thereof, will be somewhat dependent on the particular liquid 24 being coated. Those skilled in the art will appreciate that the coating liquid must be able to wet the surface of drum 22. For aqueous protein coating solutions, a drum made of Delrin�, an acetal resin sold by E.I. DuPont de Nemours and Co. of Wilmington, Del. has been found to work well.
Similarly, the drum surface speed (i.e., the circumference of the drum multiplied by the drum rotational speed) will also be somewhat dependent upon the particular liquid 24 being coated. Drum surface speeds of about 20 to 150 cm/minute (10 to 60 inches/minute) are typically used, while drum speeds of 50 to 75 cm/minute (20 to 30 inches/minute) have been found to be most useful for coating aqueous protein solutions.
Positioned above the rotating drum 22 is a microprojection member conveyor 30. Conveyor 30 includes a track 32 on which rides one or more sleds 34. Sled 34 has a plurality of microprojection members 10 a, 10 b, 10 c, 10 d, and 10 e mounted thereon. The position of the track 32 relative to the top of the rotating drum 22 is precisely controlled using micrometer-like position adjusting elements (not shown in FIG. 3). The sled 34 is adapted to move on track 32 from left to right as shown by the arrow. As the microprojection members 10 e, 10 d, and 10 c pass over the rotating drum 22, the microprojections are coated by the coating liquid 24 in the coating transfer region 25. Preferably the rotational speed of drum 22 is controlled so that the speed of the outer surface of drum 22 approximately matches the speed of sled 34 moving along track 32. In this way, there is essentially no wake created in the coating transfer region 25 by the microprojection members 10 moving through region 25. This is important in preventing any ripples/waves in the surface of the coating liquid in the coating transfer region 25 which could otherwise cause coating of the sheet 14 (see
The microprojection member coating apparatus 50 shown in
The microprojection member coating apparatus 130 shown in
The coating liquids used in the present invention are typically solutions or suspensions of the pharmacologically active agent, most typically aqueous solutions or suspensions. The coating liquids preferably have a viscosity of about 5 to 500 centipoise (cP), and more preferably about 20 to 50 cP, when measured at a temperature of 25� C. and a shear strain rate of 100 sec−1, in order to effectively coat the tiny stratum corneum-piercing elements to an appropriate thickness. The desired thickness of the solid coating on the microprojections is dependent upon the density of the microprojections per unit area and the viscosity and concentration of the coating composition as well as the coating method chosen. In general, coating thickness must be less than 50 μm since thicker coatings have a tendency to slough off the microprojections upon stratum corneum piercing. Preferred coating thicknesses are less than 10 micrometers as measured from the microprojection surface. Generally coating thickness is referred to as an average coating thickness measured over the coated microprojection. More preferred coating thicknesses are about 0.1 to 10 micrometers.
The kinetics of the agent-containing coating dissolution and release will depend on many factors including the nature of the agent, the coating process, the coating thickness and the coating composition (e.g., the presence of coating formulation additives). Depending on the release kinetics profile, it may be necessary to maintain the coated microprojections in piercing relation with the skin for extended periods of time (e.g., up to about 8 hours). This can be accomplished by anchoring the microprojection member to the skin using adhesives or by using anchored microprojections such as described in WO 97/48440, incorporated by reference in its entirety.
The apparatus and method of the present invention have particular utility with coating high potency agents requiring a dose of about 1 mg or less, preferably about 0.25 mg or less. Amounts within this range can be coated onto a microprojection array of the type shown in
Preferred drugs include desmopressin, luteinizing hormone releasing hormone (LHRH) and LHRH analogs (e.g., goserelin, leuprolide, buserelin, triptorelin), PTH, calcitonin, vasopressin, deamino [Val4, D-Arg8] arginine vasopressin, interferon alpha, interferon beta, interferon gamma, menotropins (urofollotropin (FSH) and leutinizing hormone (LH), erythrepoietrin (EPO), GM-CSF, G-CSF, IL-10, and glucagon. Preferred vaccines include vaccines for Lyme disease, influenza, hepatitis, hemophilus influenza B, tetanus, typhoid, mumps, measels, rubella, and pertusis.
In all cases, following coating, the coating solution is dried onto the microprojections by various means. In a preferred embodiment the coated device is dried in ambient room conditions. However, various temperatures and humidity levels can be used to dry the coating solution onto the microprojections. Additionally, the devices can be heated, lyophilized, freeze dried or similar techniques used to remove the water from the coating.
Other known formulation adjuvants can be added to the coating solution as long as they do not adversely affect the necessary solubility and viscosity characteristics of the coating solution and the physical integrity of the dried coating.
The following examples are given to enable those skilled in the art to more clearly understand and practice the present invention. They should not be considered as limiting the scope of the invention but merely as being illustrated as representative thereof.
A 31.0% (w/v) aqueous solution of ovalbumin was prepared by mixing for 1 hour 6.2 grams of ovalbumin (from chicken eggs, crystallized and lyophilized, salt free, sold by Sigma Chemical Co., St. Louis, Mo.) with 13.8 mL of sterile water. A 1.5% (w/v) aqueous solution of hydroxyethyl cellulose was prepared by mixing for 1 hour 0.15 g of the hydroxyethyl cellulose with 9.85 mL of sterile water. In a container were added, 6.65 mL of the ovalbumin solution, 1.40 mL of the hydroxyethyl cellulose solution, 0.26 mL of a 0.2M aqueous solution of fluorescein (a fluorescent dye used to make the coating solution, and the resultant dried coating, fluorescent) and 2.0 mL of sterile water and mixed for 1 hour. The resulting 20% ovalbumin, 0.2% hydroxyethyl cellulose, 0.005 M fluorescein solution had a viscosity of about 22 cP at a temperature of 25� C. and a rate of shearing strain of 100 sec−1.
The coating of the microprojection arrays was done using an apparatus similar to that illustrated in FIG. 3. The rotating drum had a diameter of 3.78 cm (1.49 inches). The drum was used with a coating liquid container in the form of a cylindrical trough having a diameter of 4.06 cm (1.6 inches). The drum was driven by an electric motor to turn at a rotational speed of about 2 rpm and a drum surface speed of about 23.8 cm/minute (9.36 inches/minute). The track was adjusted relative to the drum so that the sled cleared the top of the rotating drum by 0.30 mm (0.012 inches). The doctor blade was positioned so that its knife edge was spaced 0.30 mm (0.012 inches) from the drum's surface. 3 mL of the coating solution was added to the coating liquid container.
The microprojection arrays were in the form of etched and punched titanium foils, the foils having a thickness of 30 um, a width of 2.7 cm (1.07 inches) and a length of 11.5 cm (4.54 inches). The microprojections had a triangular shape (60� tip angle) and a length (measured from the surface of the foil sheet to the tip of the bent triangularly-shaped microprojections) of 250 um (0.010 inches). The arrays were attached to a sled, oriented so that the microprojections were extending away from the sled and toward the rotating drum, by means of a partial vacuum applied through openings in the side of the sled facing the rotating drum. A partial vacuum of about 0.84 atm (25 inches Hg) was applied.
The sled was propelled along the track by a spur gear mounted on the same shaft as the drum. The gear engaged a rack on the sled. The gear governed the speed of the sled along the track which was 23.9 cm/minute (9.42 inches /minute).
The microprojections extending from the sheet of the microprojection array were coated to a depth of approximately 100 um (0.004 inches). Because the coating contained fluorescein dye, the coating depth was measured using a microscope having a lamp emitting light in the UV range.
Coating experiments were performed using the device shown in FIG. 3 and described herein. Increased amounts of a model drug (sucrose) coated on the microprojection array was observed as a function of coating time. The coating solution was an aqueous solution containing 50 wt % sucrose as a model drug and had an initial volume of 2 mL. The microprojection arrays being coated were in the form of a circular metal sheet having an area of 2 cm2. The microprojection arrays were composed of titanium, had microprojection lengths of 250 μm, and a microprojection density of 321 microprojections/cm2. The microprojections were tip coated in varying temperature and humidity conditions during operation of the coating device. Coatings were performed continuously for 70 minutes. The sucrose concentration in the coating solution was measured every 10 minutes. The results of the coating solution concentration vs. time are plotted in FIG. 14. The amount of sucrose coated per array was measured and plotted as a function of time in FIG. 15.
In the first study, coating was conducted at ambient conditions (21� C., 42% relative humidity). As shown in
In the second study, coating was conducted at 5� C. and 65% relative humidity. This resulted in stable sucrose concentration during the entire duration (70 min) of the coating experiment (see FIG. 14). Analysis of the dried coatings on the microprojection tips revealed that the amount of sucrose coated was constant in cold and higher relative humidity conditions (see FIG. 15).
This experiment demonstrated that significant water evaporation was taking place in ambient conditions and that this could be minimized by conducting the coating process at lower temperature and/or higher relative humidity than in ambient conditions. Alternatively, the coating process can be conducted using a chilled coating liquid to limit evaporative loss.
In a third study at ambient conditions (21� C., 42% relative humidity), the increase in sucrose concentration as a function of coating time was minimized by constant infusion of 7 μl/min water (this water infusion rate had been calculated from the increase in sucrose concentration) into the coating solution. The results are shown in FIG. 16. Overall, these experiments demonstrate that the evolution of the coating solution is linked to evaporation of water from the coating solution. This increase in concentration is detrimental to coating reproducibility that is desirable for pharmaceutical products. This negative effect can be minimized by performing the coating process at lower temperature, at increased relative humidity, by injection of solvent (water) in the drug coating solution reservoir, and/or combinations thereof, to compensate for the solvent evaporation.
Coating experiments were performed with several drugs and model compounds using the coating apparatus shown in FIG. 3 and described herein.
Microprojection arrays were coated in cold conditions with the protein human growth hormone (hGH). Microprojection arrays (titanium sheets, microprojection lengths of 250 μm, microprojection density of 321 microprojections/cm2, 2 cm2 disc) were tip coated at 5� C. and 65% relative humidity using a 1.7 mL volume of a 20 wt % hGH, 20 wt % sucrose coating solution. Following one coating, analysis revealed that each array was coated with 3.3�0.2 μg hGH. A similar coating experiment was performed except that the microprojection arrays were coated four times with a cycle time of 5 seconds (i.e., each array was coated every five seconds). Analysis revealed that each array was coated with 9.5�0.9 μg hGH (FIG. 17). Scanning electron microscopy (SEM) of the arrays coated once and four times revealed good uniformity of coating from microprojection to microprojection with the coating limited to the tip (i.e., to the leading 120 μm) of the entire 250 μm microprojection length. This experiment demonstrated that multiple coatings could be used to increase the drug loading on the microprojection array.
Additional work was performed with the model protein ovalbumin (OVA) in order to evaluate the effect of multiple coating cycles in ambient conditions. Microprojection arrays (titanium sheets, microprojection lengths of 250 μm, microprojection density of 321 microprojections/cm2, 2 cm2 disc) were tip coated at 21� C. and 46% relative humidity using a 2 mL volume of a 20 wt % OVA aqueous coating solution. Microprojection arrays were coated 1, 2 or 4 times with a coating cycle of 5 seconds. Like in the previous experiment, increased coating amounts were obtained with an increase in the number of coatings (see FIG. 18). Also, SEM of the arrays revealed good uniformity of coating from microprojection to microprojection with the coating limited to the leading 120 μm tips of the microprojections.
Additional work was performed with the peptide growth hormone releasing factor analog (GRF) in order to evaluate the need for intermediate drying between cycles in ambient conditions. Microprojection arrays (titanium sheets, microprojection lengths of 200 μm, microprojection density of 321 microprojections/cm2, 2 cm2 disc) were tip coated at 21� C. and 46% relative humidity using the coating apparatus shown in FIG. 3 and described herein using 1.5 mL of a 7.5 wt % GRF aqueous coating solution. Microprojection arrays were coated 4, 8 or 12 times with coating cycles of 5 and 30 seconds (12 coatings were performed in 1 minute and 6 minutes with 5 second and 30 second coating cycles, respectively). Analysis of the microprojection arrays (5 arrays per condition) demonstrated good reproducibility of coating in all conditions with a trend toward decreased variability with increased number of coatings. The amount of GRF increased with the number of coatings with both coating cycle times. Higher coating levels were obtained with the longer coating cycle but the effect was surprisingly small (see FIG. 19). SEM of the arrays revealed good uniformity of coating from microprojection to microprojection with the coating limited to the leading 120 μm tips of the microprojections.
Overall, these experiments demonstrate that the coating cycle time can be shorten to as low as 5 seconds, which improves manufacturing.
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|Vaccinating devices
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|9 Nov 2004
|14 Oct 2008
|Alza Corporation
|Method and apparatus for coating skin piercing microprojections
|21 Oct 2004
|25 Nov 2008
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|Method and apparatus for reducing the incidence of tobacco use
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|7 Jul 2009
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|15 Mar 2007
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|18 Oct 2007
|4 Nov 2010
|Hisamitsu Pharmaceutical Co., Inc.
|Method Of Coating Microneedle
|27 Oct 2011
|4 Sep 2013
|Medrx Co., Ltd.
|Micro-needle coating method
|20 Jun 2006
|4 Jan 2007
|Alza Corp
|Method and device for coating a continuous strip of microprojection members
|28 Dec 2006
|26 Jul 2007
|Alza Corp
|Stable therapeutic formulations
|28 Dec 2006
|9 Oct 2008
|Alza Corp
|Stable therapeutic formulations
|23 Dec 2008
|2 Jul 2009
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|Coating method
|27 Oct 2011
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|25 Sep 2013
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|U.S. Classification
|427/287, 427/2.31, 427/256
|International Classification
|Cooperative Classification
|European Classification
|15 Mar 2002
|15 Aug 2008
|Fee payment
Year of fee payment: 4
|15 Aug 2012
|Fee payment
Year of fee payment: 8
|19 Jun 2014
Owner name: HERCULES TECHNOLOGY GROWTH CAPITAL, INC., CALIFORN
Free format text: SECURITY INTEREST;ASSIGNOR:ZOSANO PHARMA, INC.;REEL/FRAME:033203/0073
Effective date: 20140603


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text:
SpiceJet places LEAP-1B engine order; will power 42 Boeing 737 MAX aircraft
- Order valued at $1.1 billion U.S. at list price
Indian low cost carrier SpiceJet today announced the purchase 42 Boeing 737 MAX aircraft powered by CFM International's LEAP-1B engines. The engine order is valued at $1.1 billion U.S. at list price.
"We are pleased that SpiceJet has continued to place its trust in CFM," said Gaël Meheust, vice president of Sales for CFM International. "We have built a great relationship with this airline over the years and really look forward to introducing the LEAP engine into their fleet."
Aircraft Fuel Systems Market - Global Forecasts to 2020
SpiceJet, a long-time CFM customer, currently operates a fleet of more than 40 CFM56-7B-powered Boeing Next-Generation 737-800 and 737-900ER aircraft.
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Source : CFM International
Tactical Power Sources Summit 2016
Jan 25 - 27, 2016 - Washington, United States
US Export Controls with REFORM CHANGES Seminar
Jan 25 - 28, 2016 - San Diego, United States


text: Upon arrival we have been advised the pool is closed for two days - no advanced notice. May I suggest for service you come to an agreement with a neighbouring hotel and lease their facilities instead of simply recommending the beach. Towels are an issue - checked in late Friday no fresh towels until Monday. Very tired. Little atmosphere and... More


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Allan Ray
Position: Shooting Guard ▪ Shoots: Right
Height: 6-2 ▪ Weight: 190 lbs.
Born: June 17, 1984 in Bronx, New York
High School: St. Raymond in Bronx, New York
Recruiting Rank: 2002 (39)
College: Villanova University
NBA Debut: November 17, 2006
D-League: 2 G, 14.5 PPG, 2.5 RPG, 2.0 APG (Full Record)
Other Pages: College Basketball Stats, Europe Stats
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text:
Oil and gas executives gathered last month to hear about a public relations effort with a very precise target: newly hired state and federal environmental inspectors.
These atrocities are being perpetrated in our name, with our tax dollars. We must hold leaders accountable.
Gregg Levine is a contributor to Truthout and the former managing editor of Firedoglake. For more of his work, please visit his site, capitoilette. Follow Gregg on Twitter: @GreggJLevine.


text:
Golden Eyes.
The Golden Temple in Amritsar (India). Spending one day in the holy temple of the sikhs.
A photoghrafic report of the beautifull temple surrounded bij a white marble gallery and thousands of sikhs, showing respect to the holy book en the temple.
see also: www.vanvanweydom.nl
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