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After an evening in the company of the Bard, only a Lebanese banquet will do for Katherine MacAlister
It's hungry work watching Shakespeare. You can work up quite an appetite witnessing all that angst and murder, wailing and beating of chests, plotting and intrigue, betrayal and egomania.
Yes, Creation's epic production of Macbeth left us feeling rather peckish, despite the monumental slaughter taking place around us.
The trouble was, by the time they had all finished each other off it was 10pm, ruling out most restaurants. Where to go? The car knew as it meandered from Lady Margaret Hall over to Jericho, up Little Clarendon Street, parking itself right outside Al Shami on Walton Crescent where it has resided since 1988, and the perfect antidote to all the grim darkness of the Bard's famous tragedy, with its simple white interior.
Al Shami is one of my little black book entries and where I go when all else fails, my failsafe, reliable, delicious, unpretentious little backstreet favourite, open from noon to midnight every day, and where I have returned time and time again over the years, dragging visitors and friends with me whenever I get the chance.
This time it was my mother's turn and I knew she'd love the meze style cuisine and its fresh, rich, exciting collection of dishes. As she'd never been before she asked me to order and I did; the little nuggets of cauliflower served with tahini, the moist green tabbouluh, the creamy aubergine moutable, the salty halloumi in pitta and the soft fava beans in a piquant lemon dressing, with a small glass of Lebanese white wine.
The sharp witted among you will note that all these were starters but to my mind this is the best way to eat Lebanese food. Ordering several small meze dishes is far preferable to the English way of choosing a starter and a main course.
But first up the obligatory silver platter of complimentary fresh vegetables and pickles, olives and chillies which you munch through to assuage your hunger while feeling ridiculously virtuous at the same time.
Then choose from the cold meze and hot meze sections which have a plentiful supply of offerings, and while I could eat them all, six dishes between two people is more than adequate, with the prices ranging from £2.75 up to £4.80 per dish. While predominantly vegetarian, the meat and fish options stretch from spicy chicken wings to whitebait. Choosing what to have though is much harder.
We finally settled on the zahra maqlia – fried cauliflower topped with sesame oil, parsley, garlic and lemon juice (£3.50), the foul medammas – boiled fava beans in lemon juice, olive oil and garlic (£3.20), the batat harra potatoes fried in olive oil, coriander, chilli and garlic (£3.20), the kellage halloum – grilled hallomi cheese in pitta bread (£4.80), the moutable – pureed baked aubergines with sesame oil, lemon juice and garlic (£3.50), and the tabbouleh with parsley, tomatoes, onions, mint, crushed wheat, lemon juice and olive oil (£3.90), and while you may have eaten good imitations of these dishes in the past, this is the real deal; simple, delicious and bursting with flavour.
So we dined in much more splendour than the ancient king we'd witnessed; chatting, nibbling and dolling out a spoon of each dish on to our plates, which all complemented each other beautifully and all for £29, a tidy bill which Macbeth and his stringent Scottish blood would have approved of no end.
Al-Shami is open every day from noon to midnight at 25 Walton Crescent, Oxford
01865 310066 al-shami.co.uk
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- Live review: Stevie Parker @ Modern Art Oxford - 'Enthralling and tantalisingly confrontational'
- Cropredy Festival is here and Fairport Convention are 'redy' for a reunion
- Katherine MacAlister reviews The White Hart in Fyfield.....happily
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- The Royal Oak is fundraising with a Beer festival. Double whammy!
- Cowley Road Carnival's food extravaganza
- Review: Does Turtle Bay have a truly Caribbean flavour


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What is JotForm?
JotForm is a free online form builder which helps you create online forms without writing a single line of code. No sign-up required.
At JotForm, we want to make sure that you're getting the online form builder help that you need. Our friendly customer support team is available 24/7.
We believe that if one user has a question, there could be more users who may have the same question. This is why many of our support forum threads are public and available to be searched and viewed. If you'd like help immediately, feel free to search for a similar question, or submit your question or concern.
How to edit the text in my headingAsked by salamone on July 12, 2016 at 04:03 PM
I have asked this question a few times but never got a response. See my form, GBWineOrder and look at the heading. The area code is on the same line as the address and i can't figure out how to fix that. Any suggestions?Also, is there any way to submit the form and see how it will look if a customer fills it out?
Thank you. Those are probably my last two questions if the form actually works.
JotForm Support
Your question about the heading has been answered via the following thread:
And question about the form testing was answered here:
Thank you.

subset: commoncrawl


text:
What is JotForm?
JotForm is a free online form builder which helps you create online forms without writing a single line of code. No sign-up required.
At JotForm, we want to make sure that you're getting the online form builder help that you need. Our friendly customer support team is available 24/7.
We believe that if one user has a question, there could be more users who may have the same question. This is why many of our support forum threads are public and available to be searched and viewed. If you'd like help immediately, feel free to search for a similar question, or submit your question or concern.
Non profit/education discountAsked by KIPPdreamprep on September 19, 2016 at 03:33 PM
My name is Megan White assistant principal at KIPP Dream Prep. We recently had an app developed for us by School Papr LLC. They advised us to sign up for your service to allow parents to complete digital forms within the app. We a charter school that is both non profit and an educational institution. I have already purchased the bronze plan for our school but would like to upgrade to the silver. How do we apply for the non profit discount?
Thank you for your support,
Megan White
JotForm Support Manager
1. Make sure you are logged into your Jotform account KIPPdreamprep
2. Then, fill out and send this form along with your organization info (site URLand PDF docs) which will prove to us you are a real nonprofit org.
Give us up to 24 hrs to process the request. Upon approval, you should get an email like this:
IMPORTANT: When you get the "Congratulations" email with the approval, before clicking in the "Upgrade" button, make sure you have opened a fresh session at Jotform site with your account KIPPdreamprep


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Author | exchange4media News Service | Friday, Aug 23,2002 6:50 AM
A cable operator will have to offer his consumers a minimum of 33 free-to-air channels including three from Doordarshan, in the basic tier under the conditional access system to be introduced in the country soon.
The decision to give a minimum of 33 channels was taken at a meeting between the cable operators and the information & broadcasting ministry chaired by joint secretary Rakesh Mohan. A director from the ministry of finance was also present at the meeting.
No consensus on the price of the basic tier could be reached. Cable industry sources say that while the independent cable operators wanted to be allowed to charge a minimum of Rs 3 per free-to-air channel per month, the multi-system operators, especially those with interests in broadcasting as well, were keen to fix a much lower tariff of Rs 30 for the entire bouquet. Cable operators allege at for a price as low as Rs 30 for the basic tier, the cable industry would become sick.
On the other hand, broadcasters feel that if the price of the basic bouquet is very high, few consumers would opt for the pay channels.
It is learnt that after hearing the different parties out, the ministry has sought some more information on the cable industry business before deciding on the price of basic tier.
Programming HeadRadio Mango


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You've already got 5 items in your shopping cart, so there's no room to reserve another one. If you'd like, you can take something out of your cart to make room for this one.
Plot Summary
Plot: A divorced man takes his two kids to his Aunt Cly's remote farm in Turkey Hollow for Thanksgiving -- but the whole family is swept up in an adventure revolving around the "Howling Hoodoo," an elusive monster that, up until now, the townsfolk have dismissed as mere myth. Aunt Cly faces a grim holiday when a scheming neighbor frames her for turkey theft, and her beloved farm faces foreclosure. But the "mythical" Hoodoo may actually exist in reality -- in more adorable form than anyone could ever have anticipated. And the Hoodoo just may rally to the rescue of Aunt Cly and her beleaguered family.
Cast & Crew
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How to buy in-person at the Box
1. Go to Box:
2. Tap RENT & BUY GAMES
3. Tap FOR SALE
4. Select a game and complete purchase
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text: "You're wet for me" Harry says. "Is that a good thing?" I ask "Perfect" Harry is the typical high school bad boy who's afraid of love. What does he do once he cant hide from it. Harry doesn't date, right? Jess is just trying to go by her senior year as quickly as possible. The annoying jock gets in the way. He always does. She tries her best to stay away but, is it really that simple?


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Some situations call for repression of laughter, such as adorable flubs during kindergarten piano recitals and public viewings of National Treasure 2. Let loose your thunderous guffaws with today's Groupon to Chicago City Limits. Choose between the following options:
- For $7, you get two tickets to Chicago City Limits on Ice improv comedy show (a $30 value).
- For $15, you get a two-hour improv lesson from Chicago City Limits' performers and instructors (a $35 value).
Chicago City Limits' elite humorsmiths have crafted chortles for more than 30 years with family-friendly improv, sketch revues, and lessons for budding funny-bone virtuosos. The Chicago City Limits on Ice show, which runs each Friday at 8 p.m. and Saturday at 8 p.m. and 10 p.m., melds audience suggestions into uproarious skits and off-the-cuff musical numbers, producing masterpieces of controlled spontaneity. The gifted cast, whose eclectic credentials include work with Nickelodeon and a music degree from Yale, riff on current events, Jeopardy!, and spectators' daily lives, crafting a whimsical on-the-go painting as amusing as Mr. Magoo's outlandish stock portfolio. Throughout its lengthy lifespan, the company has been joined on stage by the likes of Robin Williams, Jerry Seinfeld, and Jon Stewart. Call ahead for reservations and details about each evening's program.
During a two-hour improv lesson at the group's training center, Chicago City Limit's sage performers and instructors help fledging jocularity sculptors tune into their comic muses. The course eases neophytes into improvisational scene and narrative construction and introduces them to the group's core tools of knee-slappery.


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Need a Blood Titer in Bradenton, FL? Simply order online 24/7 and get a fast, affordable Blood Titer at a lab near you (Find More Locations):
Why would I get a Blood Titer?
A Blood Titer is a blood test that checks the titer level. People in Bradenton, FL order the Blood Titer to demonstrate immunity to certain diseases.
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Our Blood Titer prices include the doctor's order that you need to get tested in Bradenton, FL, all lab fees and taxes, and a pdf copy of your results. For current prices, please CLICK HERE.
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We are delighted to offer the Blood Titer in Bradenton, FL.
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text:
לימוד לימודי יהדות
The Interdisciplinary Jewish Studies (JWS) program at Wake Forest requires 18 credit hours, from at least two departments with three courses numbering 200 or above. History, German Studies, English, Political Science and the American Ethnic Studies Departments, and the Humanities Institute offer many interesting courses as part of the Jewish Studies Minor, including American Jewish Culture, American Jewish Literature, History of European Jewry from the Middle Ages to the Present, Ancient Israel, and courses on the Middle East.
Pre-Approved Jewish Studies Minor Courses
American Ethnic Studies (AES )
- 232 The American Jewish Experience
Communications (Comm)
- 339 Practices of Citizenship
English (Eng)
- 377 Studies in American Jewish Literature
- 371 American Ethnic Literatures
- 364 Studies in Literary Criticism – Benjamin &Adorno
- Secular Jewish Communities in the Diasporas
German (Ger)
- 350 German-Jewish Literature & Culture
History (His)
- 305 Medieval and Modern Iberia
- 312 Jews, Greeks, and Romans
- 313 History of European Jewry from Middle Ages
- to the Present
- Jewish Migrations in the Americas
Politics and International Affairs (PIA)
- 259 Palestine and the Arab-Israeli Conflict
- 242 Special Topics: The Politics of Exile or
- The Politics of Exile and Diaspora
Religion (Rel)
- 113 Introduction to Jewish Traditions
- 308 Sacred Scripture in the Traditions of Abraham
- 310 Intermediate Readings in Classical Hebrew
- 314 Readings from the Rabbis
- 355 Jewish Identities: Religion, Race, and Rights
- 356 Modern Jewish Movements
- 357 Jews in the United States
Romance Languages (ROM)
- 331 Medieval Spain: A Cultural and Literary
- Perspective
The Process for Jewish Studies Program at WFU:
- Apply for acceptance into the JWS program
- Meet with an advisor to map out your program
- Take classes in a wide variety of departments and disciplines
- Take a minimum of 18 credit hours
- Enjoy your classes and learn a lot
- Complete the paperwork to receive the Jewish Studies Minor classification status at graduation
For more information about The Jewish Studies Program, please contact:
Dr. Barry Trachtenberg
Director, Jewish Studies Program


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Hands-on approach
FIRST FINANCE Institute is the premier choice institute offering such accurate, hands-on and complete certificates that promote best market practices in Capital Market and Corporate Finance.
Our long-term experience in the finance industry gives us unparalleled expertise to share foundations of real-world finance focused on operational skills rather than theoretical knowledge.
We have therefore designed best-in-class interactive training approaches that include e-learning, practice questions or classroom teamwork to resolve case studies, market-based simulations and continuous skills assessment with voting systems.


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Add a pop of playfulness to any drink with these Blue and White Dots Straws (10). You're far from ordinary, you're proud of it. Everything about you makes a statement. The world offers you a beverage, and you demand a drinking straw as bold as you are. Solid colors are boring, and why settle for stripes when you can have polka dots?
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Orders placed by 3pm CT usually ship same day.
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Author | Sumita Patra | Tuesday, Nov 21,2006 8:45 AM
Corbis, one of the world leaders in stock photography, has marked its entry into the Indian market. The company has entered into an exclusive partnership with IndiaPicture.com. In an exclusive interaction with exchange4media, Steve Davis, President and CEO, Corbis, reveals the company's India plans.
As part of the partnership over 70 million digital images from the Corbis collection would be introduced to the estimated $10 million (organised market) stock picture industry in India.
The new partnership would serve the creative needs of the growing advertising, marketing and publishing industry, which is on the constant lookout for fresh, high resolution, cost effective images.
Announcing the partnership, Davis said, "We are delighted with our partnership with IndiaPicture, who are leaders and innovators in the digital media space. We decided that the best thing to do in India was to find a great local partner, a company that understood the needs of the advertising and marketing markets of India, knows the relationships and also creates and produces wonderful pictures all about India, Indian culture and Indian ideas then we can also sell in the rest of the world."
Elaborating further on the reasons for choosing IndiaPicture.com as their partner, Davis said, "We felt that we should partner with somebody who already understood the market, already had the capabilities in different parts of the country. Another reason for picking them up was that they have local Indian production and we know that's something that not only Indian clients want but also clients around the rest of the world want. IndiaPicture.com was unique in looking at the opportunity. Corbis has lot of innovations to offer in terms of technology, in terms of customer services and in terms of new offerings and IndiaPicture.com has tremendous interesting technology for their website and other innovations. Together we can bring all that to help our clients."
Dushyant Mehta, CEO, IndiaPicture.com, said, "When we started IndiaPicture, we generated Indian content to service the Indian industry, but over a period of time we have realised that it's not possible to service them only with Indian content. You need to partner with global agency, give them a holistic content to choose from and that's where the need to partner came up. We are privileged to partner with Corbis who are leaders in this industry. So where IndiaPicture benefits is we are working with a partner who raises our standards. We feel Corbis was just was the best fit we could get."
Davis was quite bullish about garnering around 50 per cent of the market share in the organised Indian picture industry, which is estimated to grow around $10 million in the next couple of years.
While underlining a three-pronged strategy to achieve that growth, Davis said, "Great content, great customer service and really unique and new kind of innovative services are three ways that we can do great work in this market place."
He, however, did not disclose the financial details of the partnership. "The industry works in a simple way. We charge the client a fee or a license for using an image. In a partnership like this we split the fee in three ways. A part of it goes to the photographer, a part of it goes to the selling partner, and part of it goes to the partner that originates the image. So, in this case, if there is a photographer they will get the piece if we are selling IndiaPicture's content on our site then we take the piece and give some royalty to them and if they are selling then vice versa, very straightforward," he added.
Davis highlighted that both Corbis and IndiaPicture.com would help each other to create great content, use technology in the best way and do innovations. According to him, if these three areas were looked after, then "it will be a great story in India".
Programming HeadRadio Mango


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PANDORA 14ct Gold Pink Cherry Blossom Clip 750816EN40Order Code: bt5859
Bright blossoming beauty. . .
The PANDORA 14ct Gold Pink Cherry Blossom Clip charm is a touch of delightful decadence. Beautifully crafted and expertly hand finished in polished 14ct yellow gold and sumptuous pink enamel. Adorn your PANDORA collection with this pretty clip-on charm and treasure some fine florals.
Celebrate your Unforgettable Moments with PANDORA charms and jewellery, designed for you to remember your special moments, celebrate events and mark occasions. Wonderful collectable jewellery for any occasion. Show, commemorate and celebrate your love with PANDORA.
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Free Express UK Delivery (next day) is available orders £75+, otherwise it's £3.95. On orders placed before 2pm Monday-Thursday (Excludes bank holidays).
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Free Standard UK Delivery is available orders £50+, otherwise it's £1.99. Delivery 3-5 working days.
Weekend delivery is available.
Click here for full list of countries and additional delivery information
Returning an item couldn't be easier, Simply follow these instructions


text:
I think I goofed. I was experimenting with a new recipe and it called for 9 oz of white choc melted into 1 cup of cream, then to let it cool at room temp until it thickened a little. At which time it would be mixed in to 2 additional cups of heavy whipping cream. As I was making it, I thought, "Oh, ganache!" So I let the chocolate cream mixture stay on the counter overnight to wait until I did the next step today.
So this morning, the cream and chocolate is NOT a ganache. Way too liquid, so ratio was definitely off.
My question is, will I give everyone food poisoning if I use this still, or do I need to toss it and come up with plan b?
I would toss it.
The cream should be refrigerated within 2 hours. Bacteria grow rapidly at room temperature.
Ganache made with using white chocolate is usually a 3 to 1 ratio. You didn't have enougg chocolate for it to set up like ganache which is why it is still runny.
For 9oz of white chocolate, it would have been 3oz of cream (about 3 tablespoons) to make ganache.


text:
Make a Donation
The Parks & People Foundation relies on contributions from individuals, corporations and foundations to support our work in communities throughout Baltimore. Please consider making a tax-deductable donation today! Your contribution will be put to work immediately to make Baltimore a healthier and greener city.
To donate to Parks & People Foundation online using a credit card click below.
If you would like to donate by mail, please send a check or money order to:
Parks & People Foundation
2100 Liberty Heights Ave.
Baltimore, MD 21217
If you are interested in giving at work, click here.


text:
Propose Day , you can propose to the girl/boy on propose day that you have a crush on. This is the right and popular day to express your feelings, announce love, propose marriage to your partner and give special ifts like cards or flowers.
Related Post
Awesome Quotes
Good Day message Submit
All I wanted was to take care sumone 4 me
All I wanted was sumone who had b there 4 me
All I wanted was sumone who TRUE b,
all I wanted was sumone as U
Happy Day Offers
& Nbsp ;
If I reached for your hand, will u hold?
If I hold out my arms, will u hug me?
If I go to ur lips, will u kiss me?
If I capture ur heart, will u love me ??
Happy Day Offers
& Nbsp ;
As the days, my feelings get stronger,
To be in your arms, I can not wait any longer.
Look into my eyes & you'll see that it's true,
Day & Night my thought r of U ..
Happy Day offers
& Nbsp ;
"I've never seen a face so sweet
As what I was before.
My heart has left its dwelling place
and can not go.
Be with me forever. "
& Nbsp ;
N I have a heart that's true,
but now it has
gone from me u,
So, take care of him as I do,
b'coz I did not
have two naked heart.
& Nbsp ;
I open a bank account for emotional u darling
So drop your love into it and you will get the interest.
Good Offer Day.
& Nbsp ;
Excuse me, do you have a band aid
because I scrapped my knee
when I fell in love with you.
"Happy Propose Day"
& Nbsp ;
If Roses were black and violets were brown
my love for you will never be found
but roses r red and violets are blue
all I want to say is I Luv U!
"Happy Propose Day"
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February 18, 2014
Cruzeiro and Netco Sports launch the official app of the Brazilian Tricampeão
Fotofan Cruzeiro is a fun and unique way for fans to celebrate the historic club and defending Brasileiro Série A Champions
Fotofan Cruzeiro provides fans the opportunity to personalise Cruzeiro photos and share them with their friends and social networks.
Available on the App Store and Google Play, the app is free to all users and integrates various graphics and photo modification toolsincluding over ten filters and several decorative photo frames.
Fans can share their photos via social media networks Twitter and Facebook – this innovative solution will surely continue to strengthen the 2013 Champions already formidable social media presence.
Fotofan Cruzeiro is a great platform for fans to express their passion for the club through enriched user-generated content. The Cruise is the first club to activate the Fotofan platform in Brazil.Netco Sports has already released the app as a stand-alone solution as well as an integrated SDK for several clubs in Europe, including Paris Saint Germain's September 2013 launch of PSG Fotofan which has already garnered over 400,000 downloads.


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W. 270 / 106,3" D. 99 / 38,9" H. 107 / 42,1" Seat H. 44 / 17,3"
Lievore Altherr Molina, the Barcelona-based design firm blending the personalities of Alberto Lievore, Jeannette Altherr and Manel Molina, typically designs harmonious and balanced items as well as intense shapes balanced in a peaceful tension. For Driade they have designed Verlaine, a sofa complete with a square ottoman sporting an exceptionally expressive versatility that reminds of organic and flowing shapes. Its fascinating silhouette is an irresistible attraction inviting the viewer to appreciate the comfortable seat. Verlaine becomes the main aesthetic detail of the living room; it entices the eyes and grabs the attention. Sofas and pouf Upholstered left and right sofa and pouf. Polimex and MDF structure, different densities polyurethane foams padding and wooden feet. Velvet, fabric or leather removable cover. Sofas will be equipped with a back cushion with a removable cover.


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"Pilgrim pain Team care is excellent."
About: Pilgrim Hospital / Pain Management Pilgrim Hospital Pain Management PE21 9QS
Posted by gold964 (as ),
Dr. Malik and his pain Team at Phb are an excellent and caring team that gives not only excellent care but individual care and without them I could not carry on working as I do.
I cannot thank them enough for all they have done for me over the past 6 yrs.
They have believed what I have told them from the start and I have full faith in them all.
Response from United Lincolnshire Hospitals NHS Trust 14 months ago
Dear Jkirk,
Thank you so much for your kind feedback.
It is always good to receive such positive comments, and I will ensure this is passed on to all of the team.
Thank you once again, and I hope that you are doing well.
Kind regards,
Tracey Potter,
Clinical Nurse Specialist - Pain Management
gold964 thinks this response is helpful
{{helpful-1}} of {{totalOthers()}} other people think so too
- Was this response helpful? Yes | No
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text:
US Democratic presidential nominee Hillary Clinton and her Republican rival Donald Trump have once again clashed over the country's national security.
The two White House hopefuls attacked each other on Friday, with Clinton slating Trump for supporting Russian President Vladimir Putin and the business mogul calling the former secretary of state "trigger-happy."
On Wednesday, Trump criticized President Barack Obama's foreign policy as weak, saying the Russian president "has been a leader far more than our president has been."
Clinton told reporters at a news conference in New York that "it is beyond one's imagination to have a candidate for president praising" Putin.
She also said that Trump "promises to do things that will make us less safe," adding, "National security experts on both sides of the aisle are chilled by" his remarks.
Clinton said Trump's presidential campaign was not "serious," noting that it was becoming "more of a reality-television story."
Trump, who was speaking at the conservative Value Voters summit in Washington, said, "The problem is, Hillary Clinton is trigger-happy."
He described Clinton as a "massive failure," while she served as the country's top diplomat from 2009 to early 2013.
"Her tenure has brought us only war, destruction and death. She's just too quick to intervene, invade, or to push for regime change," he said at the summit.
He also said he would welcome Russia along with any other country that wants to join the US in fight against the Daesh terrorists in Syria.
"That includes Russia," he said. "If they want to join us in knocking out ISIS (Daesh), that's just fine as far as I'm concerned."
According to CNN/ORC poll released on Wednesday, both candidates remain mostly unliked, with majorities saying they have an unfavorable view of each candidate.
Polls taken in the past several months have also shown that Clinton and Trump were ranked among the most unpopular presidential candidates in America's history.


text:
Use the drop down menu above to access all of our extensive Jackson County tourism directory.
The Jackson County Tourism Directory has all the information to make your travels easier visiting Jackson County and the wonderful state of Iowa.
From wonderful wineries, rivers Mississsippi riverfront to winter and early spring eagle watching as well as everyday realities of getting to car or motorcycle worked on.
Need Camping, Kayaking, canoeing, spelunking and more? We have that too. From simple pleasures to pure sophistication Jackson County Iowa has it all.


text:
If you're gardening in U.S. Department of Agriculture plant hardiness zones 4 through 8 and scratching your head over those bare shady spaces, consider mapleleaf viburnums (Viburnum acerifolium). One of these deciduous 4- to 6-foot high shrubs spreads 4 feet. In its natural habitat, the forest understory, and in landscapes that mimic this, it quickly spreads by suckers to form a large colony. Mapleleaf viburnum performs best in well-drained soil.
How Does Your Soil Drain?
To save your mapleleaf viburnum unnecessary grief, test your soil drainage in the fall before planting in the spring. After digging and filling a 1-foot deep hole with water and letting it drain, refill and measure and record the water's depth. After 15 minutes, measure it again and subtract the result from your first measurement. Multiply by 4 to determine how many inches of water drain from the soil in an hour. If the answer is less than 1 or more than 6 inches, your soil needs attention.
Soil Drains Like Molasses
Phytophthora fungi, which thrives in poorly draining soil, may attack your viburnum's roots, crown or collar. Symptoms of infection include stunted, wilting and prematurely dropping foliage, dying twigs and branches, or oozing, cankered bark. Severely infected viburnums die. Excessive water also squeezes the oxygen out of the soil and slowly suffocates the roots. An affected viburnum has dying twigs with desiccated, wilted yellow leaves and dying twigs. Too much water, in other words, is as likely to kill your viburnum as too little.
Soil Drains Like Your Child's Favorite Drink
A viburnum planted where water drains too quickly for its roots to absorb ends up both thirsty and nutrient-deprived. Its wilting leaves, crisp along the margins, fade to yellow or brown or assume their striking fall color weeks ahead of schedule. This viburnum produces fewer flowers, and in an attempt to conserve energy, it may stop growing completely. Fortunately, the same remedy fixes slowly or rapidly draining soils. Once you've applied it, plant your viburnum with confidence.
Recipe for Perfectly Draining Soil
Improving your soil's drainage is a simple matter of altering the size of its particles. The desirable 1- to 6-inch-per-hour drainage rate belongs to loam's medium-sized, nutrient-dense particles. To achieve this, amend your dry soil with organic matter, such as compost or peat moss. Then rototill it to a 6- to 8-inch depth, cover it with a 6 to 8-inch layer of your amendment, and mix until the soil and amendment are indistinguishable from one another. This effort yields 12 to 16 inches of a well-drained, half-soil, half-amendment growing medium. With proper care, a viburnum planted in it rewards you with abundant clusters of creamy blooms, bird-attracting berries and maplelike foliage of exceptional pink to purple fall color.
Related Searches
- Manual of Woody Landscape Plants, Fifth Edition; Michael A. Dirr
- Missouri Botanical Garden: Viburnum Acerifloium
- University of California Statewide Integrated Pest Management Program: Viburnum
- University of California Statewide Integrated Pest Management Program: Collar, Foot, Root and Crown Rots -- Phytophthora Spp.
- 2001 Sunset Western Garden Book; Kathleen N. Brenzel, Editor
- Missouri Botanical Garden: Drought and Water Stress
- Utah State University Cooperative Extension: Preparing Garden Soil


text:
Two Rose Cottages Bed & Breakfast
MIDHURST, United Kingdom
Terms & Conditions
Prices are not subject to Value-added Tax (VAT), and include full English or continental breakfast. Packed lunches are also available by prior arrangement, various prices.
Prices vary by season: winter runs from 1 November 3o April, summer from 1 May to 31 October.
There is a 5% discount for stays of three or more mid-week nights in winter, and other discounts may be available at various times. Please contact us for more information.
Reservations are made by phone or e-mail, and require a deposit equivalent to one night stay, payable by check or bank transfer. Final payments can be made by cheque or in cash.
If cancellation is made more than 7 full days before the day of arrival (that is: before midnight on the same day, one week earlier), the deposit will be returned minus a 25% handling fee. Cancellations made within 7 days of the arrival day will be returned only if we are able to re-let the room, again minus 25% handling fee.
Check-in is between 4.00 and 7.00 pm, and at other times by prior arrangement.
Check-out is not later than 10.30 am on weekdays, 11.00 on weekends and bank holidays.
There is a strict no smoking policy at Two Rose Cottages. If this requirement is breached the cost of a nights stay will be chargeable, to cover the cost of deep cleaning.
We regret that we cannot accommodate pets, with the exception of service dogs. Please ring us to discuss this option.
Children over the age of 12 are welcome.


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Female 6 years old **FIV Positive** - No Symptoms DSH â White with Gray & Black Spay & Current on Vaccines Indoor Only Lexus is very sweet and loves attention. She is playful at times and independent. She would enjoy being an only cat. If you would like to give this sweet girl a home, fostered by darlene call debra 972-896-1126
Thank You!
Your message has been sent to Dallas Cat Lady Adoptions.
You'll receive a copy, too, at to help you keep track of which pets you've inquired about, and which shelters and rescues you've emailed.
NOTE: Some shelters have physical locations you can visit; some of these shelters may only have pets for a limited time, so please do not wait for a reply—just go visit the shelter! Other organizations are rescue groups run by busy volunteers who may take a while to reply. You can find information about the shelter or rescue group caring for this pet, and their adoption procedures, on the pet's details page on Adopt-a-Pet.com.


text:
My Latest Heartbreak
No, not the song by the 22-20's. The plant vandalism on campus continues. We're on year four, and I've been trying to document all the cases. The tally stands at 62 incidents in… Read More
No, not the song by the 22-20's. The plant vandalism on campus continues. We're on year four, and I've been trying to document all the cases. The tally stands at 62 incidents in… Read More
Students that have taken my class will probably remember how disdainful I was about (well, lots of things, but in this case) books on pruning. They probably still line bookstore walls, but I… Read More
Nature can teach us many things. Life, death, love. And Hope, Wisdom, and Compassion. How appropriate the 14th Dalai Lama uses 'cultivating', the act of promoting growth, to describe his wish for the… Read More
Applying for certification for Tree Campus involves a very enjoyable day of taking stock of the previous year. They ask about tree plantings, removals, dollars spent, volunteer hours, and community service projects. During… Read More
I measure my life in tree plantings. Every time I come home from the Burlington airport, I drive down Dorset street in South Burlington and visit a Blue spruce I planted on a… Read More
Everybody has their own phenologies, their own timing of spring. First day the snow shovels get put away (unused in my driveway at all this year, I might add), first day of working… Read More
Anyone around this summer, or past readers of this blog, will remember a large thunderstorm that ripped through Middlebury two days after Independence Day. Several trees were struck by lightning, which I wrote… Read More
Like most years, the landscape department takes advantage of the upcoming holiday break to do some tree removals. Not that we are doing anything under the cover of darkness-it's more like we don't… Read More
I don't know if I'm a lazy, slothful gardener, or just a brutally honest one, but either way I'm hoping for a hard frost pretty soon. I'm tired. My garden is tired. A… Read More


text:
The Angolan National Concessionaire Sociedade Nacional de Combustíveis de Angola – Empresa Pública (Sonangol) and Cobalt International Energy, Inc. (Cobalt) announced the signing of a Sale and Purchase Agreement for Sonangol to acquire all of Cobalt's 40% participating interest in Blocks 21/09 and 20/11 offshore Angola (the "Blocks") for $1.75 billion with an effective date of January 1, 2015. This transaction is subject to customary Angolan government approvals which are expected prior to the end of the year.
The Sale and Purchase Agreement provides for a smooth transition to a new operator and underscores the parties' commitment to attain the final investment decision for the Cameia development in Block 21/09 by year end 2015 in order to deliver first oil from Cameia in 2018. Notwithstanding Cobalt's continuing as operator for an interim period, all costs going forward will be borne by Sonangol.
Commenting on the transaction, Mr. Francisco Lemos José Maria, Chairman and Chief Executive Officer of Sonangol said, "Over the past seven years, Cobalt International Energy has had outstanding exploration success in Angola's pre-salt, which will accrue considerable prosperity to the Angolan people over coming generations. We are thankful and appreciative of their efforts and dedication to the task and wish them well in their future endeavors in the global industry."
Cobalt International Energy,
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text:
Broadcaster and Liverpool FC fan Colin Murray has quit talkSPORT because he will not work with The Sun.
Colin currently presents a weekday show for the sports radio station which was acquired by News Corporation from the Wireless Group in June.
He announced his decision to leave on Wednesday in a statement via Twitter, citing an "unsustainable" position because of a "future working relationship" with The Sun.
He signed off with the Twitter hashtag: "#JFT96´´ - the "justice for the 96´´ declaration relating to the Liverpool fans who died at Hillsborough in 1989.
Four days after the disaster, The Sun ran a front page story proclaiming to tell "The Truth".
The article featured claims from an anonymous policeman that some fans had "picked pockets of victims", "urinated on cops" and that some beat up a policeman who was giving the "kiss of life".
This prompted Liverpool fans to boycott the paper.
A spokesman for talkSPORT said: "It is with much regret that, after three years of working with us, Colin Murray has taken the decision to move on from his presenting role at talkSPORT this September. Colin has been a fantastic asset to the station and, while we respect his decision, we will be very sorry to lose him. We wish him all the best for the future."


text:
Follow-Up Care
It is important for you to have access to medical care after an abortion procedure. Cherry Hill Women's Center provides a 24-hour hotline for you if you are experiencing problems or have concerns after your procedure. We can also provide you a follow-up exam 2- 3 weeks after the procedure. At this appointment you can bring up any questions or concerns that you have had since your procedure, discuss birth control, or schedule an appointment for general healthcare. Pap smear and testing for sexually transmitted infections can also be performed during the abortion procedure and results are usually available at the follow-up appointment. If you are using insurance, you may be responsible for a co-pay at your follow-up appointment.
If you have had a surgical abortion with us and it is not possible for you to return to Cherry Hill Women's Center for a follow-up exam, you may choose to have your follow-up exam with your own physician. If you have had a medical abortion with Cherry Hill Women's Center, it is important that you follow up at Cherry Hill Women's Center to ensure that the procedure was completed and you do not need additional care to complete the abortion.


text:
|2010-07-18, 01:05
|Link #4
Join Date: Mar 2007
Location: SBC Gurokken
At first it sounded like some kind of Nikita/Leon thing but upon closer inspection it seems to be a reverse FMP minus the love interest (hopefully one will appear later on). The art is simple but it works well enough, plus the backgrounds are detailed (at least more detailed than I was expecting given the character art). The story... well, there's not much to speak of but it's mildly funny comedy so far.
But hey, it's got Cyrillic letters in the title. It's kind of hard to misspell this name, but we're talking about Japanese mangaka and their love of butchering foreign languages here . And the name is plausible, even though it wouldn't be my first choice since it's a bit of a unisex name, being a diminutive for both male and female names. In fact, I would first think of a guy if I heard that . Some of the other names are a horror though. Stalina? Pushkin? The names of her assassination targets make more sense than her own name lol. Although her nickname being Kortik - Dirk - is endearing.
|2010-07-18, 03:37
|Link #5
hmm...another Full Metal Panic clone.....
Assassin .....check
School premise...check
Love...........dunno...still 2 chapter
I'll try it....but if it's turn to Medaka Box version 2...I'll drop it immediately
|2010-07-20, 02:25
|Link #8
Junior Member
Join Date: Jul 2010
When you read the premise of Alyosha, it's true that FMP comes to mind immediately. But while FMP failed for me immediately, Alyosha does show some promise. Also, it's funny to read a Japanese military geek. The manga-ka sent me searching all over wiki to find out what a Levchenko cartridge is.
|2010-07-20, 04:42
|Link #9
around 100 people say the same things about FMP before they say it suck
Lets just hope this manga didn't
|2010-07-20, 11:45
|Link #10
singing heartbreak
I faintly remember reading this manga, and I suppose I didn't think much of it, because I didn't bookmark it. Guess I should try to re-read it. The story reminds me of Wild School, though that manga isn't really original =0\(but I still liked it).
|2011-03-07, 13:40
|Link #14
I just imagining ridiculous development where Miru Grandma help one of them (just like the gramps did to Alyosha) and Miru Parent also found the third Kortik and bring it to become Miru's friend too. Now, Miru have three top notch Solessia assassin walk her from home to school and become a new Kingpin. for the whole Japan
|2011-03-07, 20:28
|Link #15
Le fou, c'est moi
Join Date: Dec 2007
Location: Las Vegas, NV, USA
Age: 28
^Russ--...Solessia is the former enemy. Kortik worked for Esto--lakia. Although it's been Estolakian agents who'd been hunting Kortik lately. New regime and all that.
Aside from that, this manga is getting better and better. Magical Sewing Girl, special agent Otaku, "friendly" kiss (the author really likes the whole very close girlfriends thing), and now the Kortik twist! I like the combination of cold-blooded spy action and gentle high school comedy. Cut a thumb, give random boy pillow lap, eat cakes. Quite the life.
|action, assasin, comedy, spy thriller
|Thread Tools


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| The following article is obsolete.
This article is no longer part of the timeline. This page has not been deleted from this website for sentimental and reference purposes. You are welcome to comment on the talk page.
George Felix Allen (born March 8, 1952) is the 44th and incumbent President of the United States (2009-). Previously, he served in the Virginia state legislature, as the 67th (1994-98) and 69th (2002-06) Governor of Virginia. He is the son of former NFL football coach George Allen.


text: Quick Delivery Home! Coming Soon-Stargazer Village! The lowest priced new luxury garage townhomes in the Downingtown Area School District, set in a beautifully designed community. This Mendelssohn Home includes a gourmet kitchen, hardwood throughout main level, deck, washer & dryer and so much more!Located in the desirable Downingtown Area School District, Stargazers Village is a quiet retreat just minutes from West Chester and Exton. You'll be a short drive away are all of the daily conveniences you need - Wegmans, LA Fitness, and more! For shopping, you'll love the variety and accessibility of the King of Prussia Mall and Main Street at Exton. Call for details. 8k cash at closing when using NVR Mortgage.


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Nevermind the pictures, just posting them cause I don't want it to look so plain (yeah I'm weird). Anyways, title says it all. Have y'all ever felt like that?
Most Helpful Guy
Most Helpful Girl
Yes, I've certainly felt like that before and it's not a good feeling. In my case, it wasn't really friends making me feel that way though as it was romantic partners. I have felt like someone was "settling" for me before too and that didn't make me feel very great.11|00|0


text:
We partner with the brightest physicians in the area.
As an urologist, I currently perform minor surgical procedures and treat all aspects of clinical urology.
Before practicing in Napa, I served as a medical officer in the U.S. Air Force from 1971 to 1974, traveling around the Far East with my wife. I have two great kids and three beautiful grandchildren. We enjoy vacationing together at Lake Tahoe or visiting family in Minnesota. I am also an avid fly fisherman – I will cast a line whenever possible.
Stay in touch with our experts for the latest wellness topics and news.


text:
Hello! I am going to be deploying Symantec Endpoint in my company. There are about 7 different buildings. About 100 computers per building. What do I have to lookout for or what do I have to do in order to deploy it in the best and most smooth way?!! Thank you!
7 Replies
Jan 7, 2011 at 1:19 UTC
I would make sure you setup group update providers at each building. That way your server pushes updates out to a designated machine at each building, then all of the PCs in that building look to the group update provider for updates instead of your server pushing out updates to each PC using bandwidth. Currently, our AV updates from SEP are over 170MB. Pushing out 170MB+ to all PCs will definitely chew up bandwidth.
Also, FYI, there are some features that don't work on 64-bit operating systems such as Application and Device Control. Do some research before trying to enable these features if you have any 64-bit OS's on your network.
Jan 7, 2011 at 1:34 UTC
Thank you very much! Do you think I should have the NAV server in a different server, or can it be in the DC?
Jan 7, 2011 at 1:38 UTC
Not on the DC!
Jan 7, 2011 at 2:01 UTC
We have SEP running on a dedicated server. I'm gonna have to agree with Texkonc on this one. I wouldn't put it on your DC.
Jan 7, 2011 at 2:51 UTC
Do you know if there is a manual or something I can follow step by step?! This is the first time I will do something like this and I want to do it right.
Jan 10, 2011 at 8:03 UTC
Once you install SEP Manager you can use its help to go familiar with some terms and actions related with deployment.
SEP Manager console is quite intuitive, deployment works ok with default settings and wizards, but it is better to start up a pilot deployment on 1-5 computers. Then in practice you will know groups, policies linked to it, deplyment packages, etc work.
The most used element will be "Find Unmanaged Computers" form in Clients Tasks view, which I use to deploy SEP to computers which do not have it installed.
Jan 11, 2011 at 1:07 UTC
Synthetic Development is an IT service provider.
Make sure all the firewalls are off on the local machines, and verify DNS is working properly.
Take some time to manage Active Directory to remove any computer and user accounts that are gone.
This discussion has been inactive for over a year.
You may get a better answer to your question by starting a new discussion.


text:
With First Tutors: Music you can search for a Olney baritone horn teacher. Baritone Horn tuition are a brilliant method to start a stimulating new hobby, acquire a new skill and attain confidence with baritone horn. Please use our site to search for Olney baritone horn teachers and determine which best matches your needs so you can start your baritone horn lessons in Olney immediately!
First Tutors: Music is the best place to discover Olney baritone horn tutors in the UK, helping you find Olney baritone horn lessons close to you and Olney tutors to assist with any instrument, for example, piano, violin or guitar. We can help you find Olney baritone horn tuition or a one-to-one Olney baritone horn tutor to prepare for baritone horn exams and improve your baritone horn skills! We order Olney baritone horn tutors local to you by their hourly charges and proximity to you.
If you are a baritone horn tutor wishing to offer baritone horn lessons in Olney or throughout the UK, please register with First Tutors: Music or learn about us here. Becoming a Olney baritone horn tutor is a brilliant way to re-affirm your own knowledge by providing baritone horn lessons while helping someone else, all in Olney!


text:
Blockworld by J. Haber
Read the pages here
The first ten pages of "Blockworld" forecast a really fun, entertaining science-fiction story. Among its strengths are the characters, some of its ideas, and its dialogue.
While "Blockworld" is slightly reminiscent of a more benevolent version of "Strange Days," it seems to offer enough of its own material to make it stand out.
For example, on p.3, there is almost a spoof of the virtual sex games in both "Demolitian Man" and "Strange Days." Adam and Jennifer "gyrate" in a sexual virtual reality game, while others watch them, egging them on. It is fun, but at the same time it may come off a little awkward, all things considered.
Overall, the party atmosphere works well by introduction of the story. The cutaway to the concerned neighbors, Mr. and Mrs. Jenkins, not only adds to the atmosphere. It is also punctuated by a very funny entrance of their children, who tell them they're sleepy.
The scene with the cops arriving and the eventual arrest of Adam and Chris works well too, though the subject of barcodes will have to be clarified in full later on in the script. It is unclear how the wants determine that Adam and Chris are guilty.
The interrogation of Adam features some great dialogue on p.7:
Why don't you tell me what those things are in front of you.
No, smart-ass. These.
He pushes the games at Adam.
"Ultimate Bloodbath 3." "Combat Warriors." "Virtuana."
They yours?
They're my friend's.
Oh yeah? Where'd he get 'em?
Adam shrugs.
Pretty fancy stuff. Your friend must be loaded.
He cuts a lot of grass. With those new energy-efficient lawnmowers on the market, business has been booming.
This interrogation does however raise an issue. Namely, if people are busted for possession of games, than they should also be busted for using them. However, most of the kids at the party seem to be released.
Reader PP


text:
STAGE TUBE: Sneak Peek of Damian McGinty on GLEE!
In the November 1 episode of GLEE, (airing 8:00 - 9:00 PM ET/PT) entitled "Pot O' Gold", Will (Matthew Morrison) wants to bring some magic back to the glee club. New student Rory, (Damien McGinty, winner of THE GLEE PROJECT), makes his debut appearance and finds himself getting picked on by members of the student body.
Click below to go behind the scenes of McGinty's big GLEE debut!
No in its third season, GLEE is a musical comedy about a group of eager and ambitious students who strive to outshine their singing competition to win Nationals while navigating the cruel halls of McKinley High. Since its debut, GLEE has become a bona fide cultural phenomenon, received prestigious honors including the Golden Globe and Peabody Award and singlehandedly made glee clubs cool again.
In addition to the regular cast, GLEE has featured guest appearances by a wide range of talented performers, including Gwyneth Paltrow, who just won the 2011 Emmy Award for Outstanding Guest Actress in a Comedy Series, Carol Burnett, Kathy Griffin, Cheyenne Jackson, John Stamos, Britney Spears, Kristen Chenoweth, Idina Menzel, Jonathan Groff, Molly Shannon, Olivia Newton-John and Neil Patrick Harris, who won a 2010 Emmy Award for Outstanding Guest Actor in a Comedy Series, for his work on the show.
Click Here to Watch the Video!


text:
"Bone crushing" is often used to describe hard football hits or those machines that make baking flour out of chicken bones. Tackle a big match-up with this GrouponLive deal.
The Deal
- $15 for one ticket to see the BC Angels against the Saskatoon Sirens (a $41.50 value)
- When: Friday, September 13, at 9 p.m.
- Where: Abbotsford Entertainment & Sports Centre
- Seating: Centre rows 4–8 or Goal Line rows 1–3
- Door time: 8 p.m., though tickets may be picked up as early as 10 a.m.
- Ticket values include all fees.
- Click here to view the seating chart.
The Scouting Report
On September 13, the Legends Football League thunders into another season as the BC Angels face off against the Saskatoon Sirens. The reigning winners of last year's inaugural LFL Canada Championship, the BC Angels look to defend the crown in a season-opening rematch of the title game. Angels quarterback Mary-Anne Hanson—named MVP in the championship—returns this season to lead the offense down the field and help footballs get over their fear of flying.


text:
Search results
25,756 chatty comments by "daVinci1980"
- Posted Jun 15, 2016 11:47pm PDT If only there were an entire specialty of dentistry devoted to making teeth straight and line up in a proper bite, and if only children were highly...
- Posted Jun 15, 2016 11:53am PDT Ah yes, the slippery slope.
- Posted Jun 13, 2016 7:50am PDT Do you think that if we just got this one more terrorist group that's be the end of things? That's not how this works.
- Posted Jun 12, 2016 10:18pm PDT I think he was like 3 tries? I did a couple of practice runs (getting summoned to other worlds) to see the mechanics, then I tried to solo him a...
- Posted Jun 12, 2016 8:24pm PDT I beat Dark Souls 3. I died, a lot. I did finally start participating in co-op (which I had basically never done in any SoulsBorne game). Having...
- Posted Jun 12, 2016 8:24pm PDT I did it! in reply.
- Posted Jun 12, 2016 7:25pm PDT I don't use salt, but I understand the appeal. A little savory addition, plus it brings out the juice.
- Posted Jun 05, 2016 8:45am PDT When you abstain to vote for the candidate who you identify with on 90% of issues because the candidate you identify with on 94% of issues didn't...
- Posted Jun 05, 2016 3:47am PDT https://medium.com/@SaraJBenincasa/im-voting-for-the-democrat-in-november-because-i-m-not-a-human-tire-fire-4a3f48dff372#.oef4ttk55
- Posted Jun 04, 2016 10:49pm PDT I didn't have a banana for scale.
- Posted Jun 04, 2016 10:48pm PDT It was fucking amazing. I'll try choice again next time, but it really melted in your mouth. Very good.
- Posted Jun 04, 2016 11:15am PDT 10.80 / lb, so not actually that bad.
- Posted May 30, 2016 11:53pm PDT Yep. Go to vet, describe limping and also this hiding behavior. The vet will tell you what to do for both.
- Posted May 30, 2016 9:47pm PDT This, also harvord's post below--if you use a holy weapon they don't resurrect ever.
- Posted May 29, 2016 11:52pm PDT Could be. It's 0-60 is 0.2s slower than a Bugatti Veyron. I take people for rides in my 90D (not the P90D) and they are shocked and thrilled with...


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important thing is to have a reasonably up-to-date version to make full use of CQout's
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by Mozila one of the latest award winning, high performance browsers.
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text:
2016 Audi S8 Base Tires
Shop great prices on 2016 Audi S8 Base tires
Your neighborhood Tires Plus Total Car Care store carries great 2016 Audi S8 Base tires, all affordably priced and ready for installation. Browse the full catalog of S8 Base tires and shop tires by size, type, brand, and features. Whether you're looking for tires made for speed, stability, or fuel-efficiency, you can trust our tire experts to help you select the right tires for your ride, and to install each for maximum performance and control. Come to Tires Plus Total Car Care, where we make it simple for you to fit a tire repair or replacement into your schedule. Get started by pre-booking your appointment online and stop by when it is most convenient for you. We keep our stores open on weekends and some holidays, just for you!
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text:
Miracles will happen to you — when you begin using the magic power of your subconscious mind.
Whatever thoughts, beliefs, opinions, theories or ideas you imprint or engrave in your subconscious, you will experience them as an objective manifestation of circumstances, situations and events.
Thοse things you "register" internally, you will experience them externally. Your life has two sides, objective and subjective, visible and invisible, thought and its expression.
The thought is processed by the brain, the organ of the conscious, logical mind. When the conscious mind (or objective mind) accepts the thought completely, then it is sent to the solar plexus, called the "brain of the mind". There it takes "flesh and bones", so then to manifest into your reality.
As noted above, your subconscious has no objections. It just acts according to what is entered into it. It accepts your verdict or the conclusions of your consciousness as accomplished facts.
So, we could say that you continuously write the book of your life, since your thoughts are transformed into experiences.
The American essayist Ralph Waldo Emerson said: "Man is what he thinks all day".
Excerpt from the book "The Power of the Subconscious" by Joseph Murphy, "Dioptra" Publishing


text:
Durham Wildlife Trust is running our first ever residential weekend providing a fantastic opportunity to get to grips with how to identify bird song. Throughout the weekend our local expert from GEES will deliver indoor sessions to develop an understanding of bird song function and the 'science' of listening. This will complement dusk and dawn walks: the best time to tune in to the birds of the Land of Oak & Iron area. The full weekend will run from 1pm Saturday 8th April – 1pm Sunday 9th April. There is no charge for this course as it is part of the Geology & Wildlife Surveyors Project delivered through the Land of Oak & Iron, funded by Heritage Lottery Fund. However we would welcome donations towards an evening meal or attendees are welcome to bring their own food. Breakfast and lunch on the Sunday will be provided. Accommodation is male and female dormitory style rooms so please book early to reserve a place. For more details please email email@example.com
Bird Song Weekend
April 8, 2017 @ 11:00 am – April 9, 2017 @ 3:00 pm
Kite Rise, Highfield, Rowlands Gill
0191 584 3112


text:
Qtronix iOne Scorpius P7 PS / 2 Compact Tracball Keyboard
- $72.00
- $13.99
- $12.82
Scorpius P7 PS/2EX596671
In StockNew1 Year
Qtronix iOne Scorpius P7 Compact tracball Keyboard PS/2, Compact keyboard with integrated touchpad and 2 mouse buttons with ferrite.
- Description
Scorpius P7 - The trackball-keyboard has an enhanced slim design, which works with any IBM PS/2 compatible computer. As there is no need for an additional mouse, this keyboard is the perfect match for home entertainment or industrial needs. Utilizing the latest in rubber mechanical key switch technology, the Scorpius P7 offers durability and style that will enhance any system for years to come. Features: Great performance in business applications with optical trackball, Standard left and right mouse button function. (Similar to Cherry G84-4400 keyboard)
- Compact size
- Built-in 14mm optical trackball
- 2 mouse buttons
- Flat keys
- 2,5 m cable with ferrite
- Rubber mechanical keyswitch
- Fits to 19" racks
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text: Editor's Note: Any reference to TheStreet Ratings and its underlying recommendation does not reflect the opinion of TheStreet, Inc. or any of its contributors including Jim Cramer or Stephanie Link. All three major indices are trading down today with the Dow Jones Industrial Average ( ^DJI) trading down 34 points (-0.2%) at 15,991 as of Tuesday, Dec. 10, 2013, 11:45 AM ET. The NYSE advances/declines ratio sits at 1,256 issues advancing vs. 1,637 declining with 176 unchanged. The Materials & Construction industry currently sits up 0.1% versus the S&P 500, which is down 0.2%. A company within the industry that fell today was Stericycle Incorporated ( SRCL), up 0.6%. Top gainers within the industry include Lennar Corporation ( LEN), up 2.4%, DR Horton ( DHI), up 0.9%, Weyerhaeuser ( WY), up 0.8% and Cemex S.A.B. de C.V ( CX), up 0.8%. TheStreet would like to highlight 3 stocks pushing the industry lower today: 3. MDU Resources Group ( MDU) is one of the companies pushing the Materials & Construction industry lower today. As of noon trading, MDU Resources Group is down $0.16 (-0.6%) to $29.26 on light volume. Thus far, 108,348 shares of MDU Resources Group exchanged hands as compared to its average daily volume of 570,700 shares. The stock has ranged in price between $29.20-$29.50 after having opened the day at $29.20 as compared to the previous trading day's close of $29.42. MDU Resources Group, Inc. operates as a diversified natural resource company in the United States. The company's Electric segment generates, transmits, and distributes electricity in Montana, North Dakota, South Dakota, and Wyoming. MDU Resources Group has a market cap of $5.6 billion and is part of the utilities sector. The company has a P/E ratio of 48.1, above the S&P 500 P/E ratio of 17.7. Shares are up 40.4% year to date as of the close of trading on Monday. Currently there are 4 analysts that rate MDU Resources Group a buy, no analysts rate it a sell, and 4 rate it a hold. TheStreet Ratings rates MDU Resources Group as a buy. The company's strengths can be seen in multiple areas, such as its revenue growth, largely solid financial position with reasonable debt levels by most measures, good cash flow from operations, increase in net income and solid stock price performance. We feel these strengths outweigh the fact that the company has had somewhat disappointing return on equity. Get the full MDU Resources Group Ratings Report now. STOCKS TO BUY: TheStreet Quant Ratings has identified a handful of stocks that can potentially TRIPLE in the next 12-months. Learn more.


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Water can collect in a basement due to many reasons: flooding, excessive rainfall, washing machine malfunction or leaking or broken pipes. Even the extent of water can vary, from a minor flood with tiny puddles all over the floor to a full-scale flood with several feet of water. No matter what the degree, immediate removal of water is necessary to prevent damaging the items in the basement, mold and mildew from developing and an unpleasant odor from arising. Make sure you turn off the electricity in the basement before entering to prevent accidents or chances of electrocution.
Things You'll Need
- High boots
- Gloves
- Dry towels or mop
- Plastic bucket
- Sump pump or portable pump
- Garden or drain hose
How to Get Rid of Water in My Basement
Assess the extent of the water in the basement. If your basement has tiny puddles of water, use a dry towel or a mop over them and drain excess water into a bucket. Keep doing this until all the water is soaked away and collected in the bucket. Open windows to allow fresh air to come inside, and turn the electricity back on so you can run a fan to dry up the floor.
Rent a sump pump if you do not own one for a major flooding with several feet of water in the basement, draining out 2 feet of water every 24 hours. Pumping more aggressively could weaken the outside soil, causing the basement to cave in. An alternative to a sump pump is to use two or more portable small pumps, but make sure you connect these to a large diameter drain hose or garden hose. Also remove the water as far away from your house as you can to prevent it from reentering the basement. Begin pumping either from the section of the basement that will sustain the most damage due to floodwater or from the highest point where the accumulated water is at the lowest level.
The amount of days it will take to remove all the floodwater from the basement will depend on its size and the amount of accumulated water. It could take anywhere from one day to several days since you will not be draining out more than 2 feet every 24 hours. Once all the water is removed, turn on the fans and open all the windows to dry out your basement. Prevent opening windows if it is raining outdoors, and work with fans only. You can also use a dehumidifier to dry the basement, but make sure all the doors and windows are shut before you turn it on.
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To determine the active site in the Heparin II (HepII) domain of fibronectin that regulates outflow facility in cultured anterior segments and disrupts the actin cytoskeleton in transformed human trabecular meshwork (TM-1) cells.
Outflow facility was determined by two-level, constant-pressure perfusion in cultured anterior segments of rhesus and cynomolgus monkey eyes. One segment from each pair was exchanged with either the HepII domain or an integrin/syndecan binding peptide (IDAPS or PPRARI) from the HepII domain. To assay changes in the actin cytoskeleton, TM-1 cells were incubated for 24 hours with or without the HepII domain, PPRARI, or IDAPS. Changes were monitored with phase and immunofluorescence microscopy.
HepII domain (100 µg/mL) and PPRARI (500 µg/mL) increased outflow facility by 31% ± 13% (n = 9, P < 0.05) and 24% ± 9% (n = 8, P < 0.05), respectively in cultured anterior segments after an overnight infusion. Perfusion with IDAPS (500 µg/mL) had no effect on outflow facility. In TM-1 cultures, 250 µg/mL of the HepII domain or 4 mg/mL of PPRARI disrupted the assembly of actin filaments. A lower concentration of PPRARI (2 mg/mL) disrupted the actin cytoskeleton when used in combination with a nondisrupting concentration of the HepII domain (30–60 µg/mL). In contrast, IDAPS did not disrupt the actin cytoskeleton under any condition tested.
The active site in the HepII domain that regulates outflow facility in cultured anterior segments and disrupts the actin cytoskeleton in TM-1 cells is the syndecan/integrin binding sequence, PPRARI.
Aqueous humor drainage via the conventional outflow pathway accounts for one half to two thirds of the total aqueous outflow in a healthy human eye.1,2 One feature that contributes to outflow resistance via this pathway is the contractile property of the trabecular meshwork (TM). Thus, agents that disrupt the organization of the actin cytoskeleton, cell–cell junctions, and cell-matrix contacts that maintain tissue integrity tend to increase outflow facility in enucleated human and bovine eye organ perfusion cultures and in live monkey eyes.3 In contrast, agents that support actin cytoskeleton assembly increase resistance and reduce outflow facility.4
It is well established that signaling events mediated by the extracellular matrix (ECM) play a critical role in maintaining tissue architecture by regulating the organization of the actin cytoskeleton and cell contacts. Hence, these signaling events could regulate outflow facility. Recent studies support this idea and show that the Heparin II (HepII) domain of fibronectin, an ECM protein found in the TM, increases outflow facility when perfused through cultured human anterior segments.5 Presumably, this domain increases outflow facility by mediating the disassembly of the actin cytoskeleton in TM cells.6
The HepII domain is a 30-kDa region of fibronectin that comprises the 12th to 14th type III repeats. It plays an important role in regulating the organization of the actin cytoskeleton by acting as a ligand for members of the syndecan and integrin family of receptors. Syndecans and integrins control the organization of the actin cytoskeleton by activating signaling pathways involving Rho GTPases.7,8 Integrins comprise a large family of heterodimeric receptors that usually bind ECM proteins through homologues of the tripeptide sequence, Arg-Gly-Asp (RGD). The HepII domain contains one RGD homologue (IDAPS) in the 14th repeat.9 Another integrin binding sequence, PPRARI, is also found within the 14th repeat.10 Both these sequences are believed to bind α4β1 integrins. Syndecans, on the other hand, are transmembrane heapran sulfate proteoglycans (HSPGs) that interact with ECM proteins via their sulfated glycosaminoglycan side chains. Binding of syndecans, especially syndecan-1 and -4, to fibronectin and the HepII domain is mediated by regions of positively charged residues located in the 13th repeat,11 as well as by the sequence PPRARI.12
In this study, we investigated the role that the integrin/syndecan binding sites, PPRARI and IDAPS, in the HepII domain may play in regulating outflow facility. This study showed that PPRARI, but not IDAPS, increased outflow facility in monkey anterior segments ex vivo as well as disrupted the actin cytoskeleton of TM cells in vitro. This suggests that the active site in the HepII domain responsible for increasing outflow facility is the PPRARI sequence and that an integrin- and/or syndecan-mediated signaling pathway may be involved.
Immortalized human TM-1 cells were grown in low-glucose Dulbecco's modified Eagle's medium (DMEM) containing 10% fetal bovine serum (Atlanta Biologicals, Inc., Norcross, GA), 2 mM l-glutamine, 2.5 µg/mL amphotericin B, and 25 µg/mL gentamicin, as previously described.13 For experiments, confluent cultures grown on glass coverslips were incubated overnight in serum-free DMEM containing 2.5 µg/mL amphotericin and 25 µg/mL gentamicin in the absence or presence of the HepII domain, PPRARI, PPRAAI, or IDAPS. Serum-free medium was used to avoid interactions between the HepII domain and serum factors such as plasma fibronectin.
The recombinant HepII domain was made as described previously.14 The peptides: PPRARI, IDAPS, PPRAAI, IEAPS, and EILDV, an α4β1-integrin-binding peptide found in the V region of fibronectin,15,16 were synthesized at the Biotechnology Center of the University of Wisconsin-Madison. Peptides were synthesized on a 25-micromole scale by an automated synthesizer (model 432A; Applied Biosystems, Inc. [ABI], Foster City, CA). The cleaved peptides were precipitated with cold t-butylmethylether and their mass confirmed by electrospray ionization mass spectroscopy. The purity of the peptides was determined by HPLC. The activity of the PPRARI peptide has been attributed to the two argininyl residues in the peptide. Deletion of either residue reduces the activity the peptide, but does not completely abolish it.10 A peptide lacking both argininyl residues could not be used, since this peptide was insoluble. Sequence homology between the HepII domains in human17 and rhesus monkeys (REFSEQ:accession XM_001083548.1) is 99%. IDAPS and PPRARI have 100% sequence homology between humans and monkeys.
TM-1 cells were permeabilized with 0.5% Triton X-100, fixed with 4% paraformaldehyde and then incubated with Alexa 488-conjugated phalloidin (0.67 U/mL; Invitrogen, Carlsbad, CA) in 0.1% BSA/PBS for 1 hour as previously described.6,18 Cells were labeled with Hoechst 33342 (Invitrogen) to localize nuclei. Coverslips were mounted (ImmuMount; Shandon Lipshaw, Pittsburgh, PA). All images were acquired using a digital camera (AxioCam HRm; Carl Zeiss Meditec, Inc., Thornwood, NJ) mounted on an epifluorescence microscope (Axio-plan 2 Imaging; Zeiss) equipped with image analysis software (Axio-Vision ver. 4.5; Zeiss).
A cell-viability assay (Live/Dead; Invitrogen) was used to evaluate cell viability in the absence or presence of increasing concentrations of PPRARI after 24 hours. The cells were lifted off the dish with a cell dissociation buffer (Sigma-Aldrich, St. Louis, MO), stained with calcein AM and ethidium homodimer-1, and analyzed by flow cytometry. In some experiments, cells were labeled while still attached to dishes and then examined by fluorescence and phase microscopy according to the manufacturer's protocol. TM-1 cells treated with 0.1% saponin in PBS for 10 minutes were used as a positive control of cell death.
Anterior segments were obtained from either rhesus (Macaca mulatta; n = 14) or cynomolgus (Macaca fascicularis; n = 9) monkeys from the Wisconsin National Primate Research Center, Covance Inc. (Madison, WI), Dr. Kaufman's colony, or colonies from other investigators at the University of Wisconsin. The experimental protocol adhered to the ARVO Statement for the Use of Animals in Ophthalmic and Visual Research. Eleven monkeys had had no prior ocular procedures and were euthanatized due to weight loss and chronic diarrhea. Four cynomolgus monkeys had their anterior chambers perfused >6 months before being euthanatized. Two cynomolgus monkeys underwent long-term treatments with echothiophate iodide to cause accumulation of ECM. These treatments ended 1 to 3 years before being euthanatized, and the intraocular pressures were normal. One rhesus had a bilateral iridectomy 8 months before being euthanatized and cholinergic agonist treatment 2 weeks before being euthanatized. Another rhesus had a single retinal laser lesion 8 months before being euthanatized. Other monkeys had been used in nonocular studies that included vaccine testing (n = 2), fetectomy (n = 1), ovariectomy (n = 1), kidney donor (n = 1), and cerebral infarction (n = 1). The anterior segments were placed in culture within 2 hours after death, as previously described.19 Anterior segments were cultured in high-glucose DMEM containing 0.584 g/L l-glutamine, 15mg/l-gentamicin, 100U/mL penicillin G, 100 µg/mL streptomycin sulfate, and 0.25 µg/mL amphotericin B at 37°C with 5% CO2. Media were infused with an infusion pump (PHD 2000; Harvard Apparatus, Holliston, MA) at a constant rate of 2.5 µL/min.
After 1 to 3 days of equilibration, baseline outflow facility was measured for 1 hour by two-level, constant-pressure perfusion.20 Once a stable baseline was obtained, one of the paired segments was exchanged with 3 to 3.5 mL of media containing either the HepII domain or a peptide. The peptide concentration used was based on the concentration shown to give a maximum effect in vitro.12 The contralateral segment was exchanged with the same volume of DMEM. The infusion was stopped for 2 to 4 hours to allow the HepII domain or peptides to competitively bind. Infusion with the corresponding solution was then continued overnight. The highest concentration of the HepII domain (833 µg/mL) was infused for only 4 to 5 hours, followed by an overnight vehicle infusion. Outflow facility was measured the next day.
To test the effect of the control peptides, the wild-type peptides were washed out with DMEM for 1 to 3 days, and a new baseline outflow facility was established. The initial control segments were then exchanged with the same dose of control peptides and the previous peptide-treated segments were exchanged with DMEM. Outflow facility was monitored as described above.
The effect of the HepII domain or peptides on outflow facility (exp) is expressed as the ratio of posttreatment outflow facility (Rx) compared to baseline (BL) and corrected for control (con) eye washout: (Rxexp/BLexp)/(Rxcon/BLcon). The percentage of change in outflow facility was calculated as [(Rxexp/BLexp)/(Rxcon/BLcon) − 1] × 100. Statistical analysis was performed with a two-tail paired t-test. A Mann-Whitney U test was used to determine whether the treatments differentially affected rhesus and cynomolgus monkeys.
Monkey organ cultured anterior segments (MOCAS) were exchanged with 6 mL of 4% paraformaldehyde over 30 minutes. Each segment was then cut into quadrants and immersed in 4% paraformaldehyde. Quadrants were embedded in either resin (JB-4; Polysciences Inc., Warrington, PA) or paraffin. Sagittal sections, 4 to 5 µm thick, were cut and stained with either toluidine blue (Polysciences Inc.) or hematoxylin and eosin. Sections were examined for the presence of TM cells, beams, and the integrity of Schlemm's canal. All four quadrants per anterior segment were examined.
Previous studies had shown that the HepII domain increased outflow facility in cultured human anterior segments (HOCAS). 5 To determine whether the activity of the HepII domain involved one of the two known integrin/syndecan binding sites (IDAPS and PPRARI) in the HepII domain (Fig. 1), MOCAS were perfused with either the intact HepII domain or one of the synthetic peptides, PPRARI or IDAPS. A recombinant HepII domain containing mutations in these sites could not be used, because circular dichroism analysis indicated that these mutations affected the conformation of the HepII domain (data not shown). As shown in Figure 2 and Table 1, 100 µg/mL of the HepII domain increased outflow facility by 31% ± 13% (n = 9; P < 0.05) on the day after exchange. Among the nine pairs of MOCAS perfused with 100 µg/mL of the HepII domain, two MOCAS did not respond, and two MOCAS showed a decrease in outflow facility. The effect of the HepII domain on outflow facility appeared to be dose dependent, although only two pairs of MOCAS were studied at each of the other concentrations. At a lower concentration (10 µg/mL), the HepII domain did not have any effect on outflow facility (n = 2), whereas the higher concentration (833 µg/mL), which previously increased outflow facility in HOCAS,5 decreased outflow facility by 80% ± 16%, 4 to 5 hours after exchange (data not shown). The decrease in outflow facility caused by the higher concentration was still present the next day despite an overnight infusion with media containing only vehicle (see Materials and Methods).
Overnight infusion with PPRARI also increased outflow facility by 24% ± 9% (n = 8, P < 0.05), similar to that observed with the HepII domain. As shown in Figure 2 and Table 2, the mutant PPRAAI (n = 6), which has a lower activity (see Materials and Methods), did not significantly increase outflow facility (12% ± 9%). Infusion with IDAPS, the mutant peptide IEAPS (Fig. 2, Table 3) or the β1 integrin binding peptide EILDV (data not shown) had no significant effect on outflow facility. There were no statistically significant differences in outflow facility between rhesus and cynomolgus monkeys within any of the treatment conditions. Washout of the HepII domain or PPRARI after exchange or overnight infusion with plain medium resulted in the return of outflow facility to near baseline levels when corrected for control eye washout (ratio treated/vehicle for baseline postwashout/baseline pretreatment = 1.15 ± 0.08; n = 14, not significant).
Light micrographs show that gross changes were not observed in the juxtacanalicular tissue (JCT) or Schlemm's canal in MOCAS perfused with PPRARI, PPRAAI, or the HepII domain compared with control anterior segments (cf. Fig. 3A and 3B–D). In all the MOCAS, beams were intact, and cells were observed within the JCT and lining Schlemm's canal (Fig. 3).
In TM-1 cultures incubated with 2 mg/mL of PPRARI a reduction in assembled actin filaments could be observed compared to nontreated cultures or cultures incubated with the PPRAAI mutant (Fig. 4). Neither the PPRAAI mutant nor IDAPS altered the assembly of the actin cytoskeleton compared to control cultures (Fig. 4). If PPRARI was used in combination with a low concentration (30 µg/mL) of the HepII domain that did not trigger the disassembly of actin filaments (Fig. 4), assembled actin filaments were no longer observed, and large gaps between cells appeared (Fig. 4). As shown in Figure 5, the gaps were dependent on the concentration of the HepII domain.6 Gaps were also apparent when the HepII domain (60 µg/mL) was used in combination with 2 mg/mL of PPRARI (Fig. 5G). Neither concentration alone caused a significant disruption in cell–cell interactions (cfs. Fig. 5B and 5F).
Cultures incubated with the PPRAAI mutant contained some actin filaments, but the filaments were smaller compared to control cultures and larger compared with cultures treated with PPRARI and the HepII domain (Fig. 4). These cultures also exhibited fewer gaps between cells compared to cultures incubated with PPRARI and the HepII domain (Fig. 4). This result supports previous findings that PPRAAI has a lower activity. The effect appeared to be specific for PPRARI and PPRAAI, because when IDAPS was used in conjunction with the HepII domain, actin filaments could still be observed (Fig. 4). Coincubation with IDAPS (2 mg/mL) and PPRARI (2 mg/mL) did not enhance the effect of PPRARI and assembled actin filaments were still observed (data not shown).
Treatment of TM-1 cultures with higher concentrations of PPRARI (4 mg/mL) in the absence of the HepII domain led to a disassembly of actin filaments (Fig. 4) and the appearance of gaps between cells compared to untreated control cultures (Fig. 5H). However, PPRARI was not as effective as 250 µg/mL of the HepII domain which completely abolished the assembly of actin filaments (Fig. 4) and caused large gaps between cells (Fig 5D). At 4 mg/mL, the PPRAAI mutant also reduced the assembly of actin filaments and caused gaps between cells (Fig. 4), but the gaps were smaller and fewer in number, suggesting that its activity was reduced compared to PPRARI. In contrast, TM-1 cultures treated with 4 mg/mL of IDAPS appeared similar to untreated controls and exhibited numerous actin filaments.
Treatment with PPRARI for 24 hours was not toxic to cultures at 500 µg/mL, which was the concentration used in MOCAS and at 2 mg/mL. At these concentrations, the majority of TM-1 cells appeared healthy and well spread, similar to that observed in untreated controls (cf. Fig. 5A, 5E, 5F). The viability assay confirmed this observation and showed that less then 9% of the cells in cultures treated with 2 mg/mL PPRARI were nonviable compared to control cultures. Higher concentrations of PPRARI (4 mg/mL) appeared slightly toxic, as cell viability decreased by 18% compared with the control. Presumably, this decrease occurred because 4 mg/mL of PPRARI caused some cells to lift off the plates and undergo anoikis, which is a specific form of apoptosis that is induced when anchorage-dependent cells are detached from the surrounding ECM for a prolonged period (Fig. 5H).
This study demonstrates that the site in the HepII domain responsible for increasing outflow facility may be the integrin/syndecan-binding sequence, PPRARI. A synthetic peptide of this sequence was able to increase outflow facility by 24%, similar to the 31% increase in outflow facility caused by the HepII domain in cultured anterior segments. The effect was specific for PPRARI, since neither the mutated PPRAAI peptide nor the integrin-binding peptides (IDAPS, EILDV) were able to increase outflow facility to the same extent when perfused into cultured anterior segments. PPRARI also showed an ability to disrupt the assembly of actin filaments and cause large gaps between cells. A similar result was seen in TM-1 cultures when the HepII domain disrupted the assembly of actin filaments and cell–cell contacts.6 This suggests that the HepII domain and PPRARI may affect similar mechanisms.
Although the biological effects of PPRARI and the HepII domain were similar, the activity of PPRARI was much weaker. In MOCAS, the concentration of the HepII domain needed to increase outflow facility was 3 µM compared with the concentration of 627 µM needed for PPRARI. A higher concentration (5 mM) of the peptide was also necessary to disrupt the actin cytoskeleton of TM-1 cells. A lower concentration of PPRARI was able to disrupt the organization of the actin filaments but only if a low, inactive concentration of the HepII domain was also present. The reason for this is unclear. There may be an additive or synergistic relationship between PPRARI and the HepII domain. For instance, PPRARI and the HepII domain may activate different receptors, but the signals generated converge to induce the disruption of actin filaments in TM-1 cultures. However, it may simply be that the PPRARI sequence exists in a specific conformation in the HepII domain and that the smaller peptide, out of context, has a much lower affinity for its receptor and hence higher concentrations are needed. This has clearly been shown to be the case for other integrin binding peptides. For instance, the α4β1 integrin-binding peptide LDV is 10 to 20 times less effective than the larger CS1 fragment (2700 µM compared with 180 µM)21 and a small α9β1 integrin-binding peptide requires a concentration of 1000 µM to inhibit cell adhesion by 50%.22
The time course and concentration of the HepII domain required to elicit an effect in MOCAS differed from that previously observed in HOCAS. In HOCAS, the concentration of the HepII domain that increased outflow facility was eight times greater than that used in the MOCAS (833 µg/mL versus 100 µg/mL) and the increase in outflow facility was approximately four times greater (90% vs. 24%).5 The response in HOCAS was also faster and occurred within 3 hours. The reason for these differences is an interesting question. Both the HepII domain and PPRARI bind heparan sulfates on syndecans and other HSPGs.23–25 Thus, there may be differences in the relative density of HSPGs in MOCAS compared to HOCAS, resulting in higher doses of the HepII domain clogging the meshwork and lower doses taking longer to have an effect. MOCAS were also placed in culture sooner than the HOCAS. Thus, autolysis in the HOCAS could have weakened interactions in the TM, allowing the effects of HepII domain to occur more rapidly.
The percentage of MOCAS that responded to the HepII domain also differed from HOCAS; 55.5% of MOCAS responded to the HepII domain, whereas 90% of HOCAS responded.5 This result suggests that humans are more responsive to the HepII domain. Of note, HOCAS, unlike MOCAS, seemed to have two populations of responders: 50% of the HOCAS were low responders, showing a 20% to 50% increase in outflow facility, and 40% were high responders, showing a 101% to 400% increase.
The PPRARI sequence in the HepII domain has been reported to bind both α4β1 integrins and syndecan-4.10,23 Thus, either of these receptors could be responsible for increasing outflow facility in MOCAS. Both receptors are found in the TM,26,27 and both activate signaling pathways involving Rho GTPases8,28 which control outflow facility. 29–33 At first glance, α4β1 integrins would not seem to be the receptor for the HepII domain. In subconfluent TM cultures, the HepII domain used α4β1 integrins to activate stress fiber formation,18 not to disassemble them. In addition, perfusion with the α4β1 binding peptide IDAPS did not increase outflow facility or trigger the disassembly of actin filaments in TM-1 cultures. However, since IDAPS binds to the β1 subunit of α4β1 integrins and PPRARI is believed to bind to the α4 subunit,10 PPRARI and the HepII domain could be using another α4 integrin, such as α4β7 which frequently shares common ligands with α4β1.34–38
Responses to cell-matrix signaling events are influenced by cross-talk from other ECM receptors and cadherins in cell-cell contacts.39–42 Hence, it is not surprising that confluent TM-1 cultures responded differently to the HepII domain, as opposed to subconfluent HTM cultures,6,18 by disassembling actin filaments. In the subconfluent studies,18 the only matrix present was two purified domains from fibronectin. In contrast, confluent TM-1 cultures13 contain type IV collagen, laminin, thrombospondin, and cell–cell contacts.43 Which receptors cosignal with the HepII domain is not known.
In summary, this study demonstrates that a specific site in the HepII domain, associated with cell-matrix signaling events and involved in the regulation of cell contractility, is responsible for altering outflow facility. This is the first time a specific cell-matrix interaction has been shown to alter outflow facility and provides a glimpse into the possible mechanisms used by the ECM to regulate outflow facility. Understanding how the ECM functions in the TM should provide new pharmacologic targets for the control of intraocular pressure.
Supported in part by National Eye Institute Grants EY012515, EY017006 (DMP), and R01 EY002698 (PLK), Research to Prevent Blindness, Ocular Physiology Research and Education Foundation (PLK), Research Resources Grant P51 RR000167 to the Wisconsin National Primate Research Center, and Core Grant P30 EY016665 to the Department of Ophthalmology and Visual Sciences.
Disclosure: J.M. Gonzalez, Jr., None; Y. Hu, None; B.T. Gabelt, None; P.L. Kaufman, None; D.M. Peters, None
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