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The 2014 Republican Party of Minnesota State Convention is completed and my predictions on who would be endorsed for the U.S. Senate and governor were off the mark. So what happened at the convention?
The attendance at the convention was low and with contested endorsements for U.S. Senate and governor, this is unprecedented in the modern history of party conventions.
Overall, the convention was well organized. I've been to 17 state convention (both DFL & GOP) and the Republican Party of Minnesota ran a very efficient and orderly convention. The voting was timely, the WIFI was great, and party staff were very helpful the entire convention.
U.S. Senate – Mike McFadden
As I wrote in my predictions, there were a high number of undecided delegates and alternates for the U.S. Senate endorsement. But instead of five candidates seeking the endorsement, six candidates gave speeches and presentations at the convention. Phillip Parrish did have difficulty meeting the signature requirement, but was given an extension to gather the additional signatures.
The six candidates seeking the endorsement were:
- Jim Abeler
- Chris Dahlberg
- Mike McFadden
- Monti Moreno
- Julianne Ortman
- Phillip Parrish
The speeches and presentations by the candidates were very important, especially with so many undecided delegates and seated alternates determining who would be endorsed. After the speeches, I wrote the candidates would be much closer in totals than expected.
As predicted, this turned into a three-person race for the endorsement: Dahlberg, McFadden, Ortman. But what couldn't be predicted is how Ortman's campaign would collapse at the convention. Her speech and presentation was very flat and her campaign quickly spiraled out of control soon after Ortman came in third place on the first ballot.
Dahlberg did have a strong showing on Friday, as he gave a good speech and presentation. Dahlberg would remain in the lead for eight ballots, but he lost the endorsement to McFadden on the tenth ballot.
McFadden's campaign had the best organization at the convention during the U.S. Senate endorsement. McFadden's campaign simply outworked and outsmarted the other campaigns throughout balloting, which lasted over two days. Tom Emmer's campaign, led by David FitzSimmons, helped McFadden's campaign at the convention.
The key vote in the U.S. Senate endorsement was the vote to recess the convention at 2 AM on early Sunday morning just after the seventh ballot. Dahlberg was leading in the ballot and was close to being endorsed, but his campaign didn't resist the recess. Delaying the vote stalled Dahlberg's momentum. It was a strategic mistake and cost Dahlberg the endorsement.
While others slept, McFadden's campaign stayed up and worked through the night, preparing for the balloting to start again. McFadden's campaign began the day by announcing an endorsement from Congresswoman Michele Bachmann. McFadden gained on the eight ballot, took the lead on the ninth ballot and won the endorsement on the tenth ballot.
It is worth noting that McFadden was booed when his name was first announced, but McFadden later won the crowd over and received the endorsement. Candidates that are booed don't usually get endorsed. McFadden's victory was impressive.
McFadden's campaign team outworked the other campaigns and with the Republican Party of Minnesota's endorsement for the U.S. Senate, McFadden has been propelled from the convention with a boost of energy.
Republicans endorsed the strongest candidate to run for the U.S. Senate against U.S. Senator Al Franken.
Governor – Jeff Johnson
The endorsement for governor was completely separate than the endorsement for U.S. Senate – McFadden is a different candidate than Jeff Johnson. Two separate races, two different endorsements. But as predicted, the endorsement fight for governor was more combative than the endorsement for U.S. Senate.
The four candidates seeking the endorsement were:
- Jeff Johnson
- Marty Seifert
- Dave Thompson
- Rob Farnsworth
This quickly turned into a three-person race for the endorsement: Johnson, Seifert, Thompson. As I wrote, Johnson and Thompson aligned, with Thompson ending his campaign and endorsing Johnson after the third ballot.
As in the endorsement for the U.S. Senate, the speeches and presentations by the candidates for governor were very important. Johnson's campaign had the best visual presence (banners, signs, posters, etc.) and organization at the convention. But Johnson came into the convention low on resources and likely spent a large portion of his money for the convention.
While McFadden raised the most money out of the Republican candidates for U.S. Senate, Johnson has struggled with fundraising. Johnson's fundraising total for the first quarter of 2014 was very low, only raising $32,027. Johnson leaves the convention on fumes, trailing some of his rivals in the Republican primary other candidates in fundraising.
One of the more dramatic events at the convention happened when Marty Seifert addressed the convention after the third ballot. Seifert released his delegates and announced he would be running in the Republican primary. Seifert's speech upset the leadership of the Republican Party of Minnesota and supporters of Johnson, as delegates left the convention. Click here for a post from Jeff Kolb about the reaction to Seifert's speech.
It is not the responsibility of Seifert's campaign to produce the delegates for Johnson to receive the endorsement. The lack of enthusiasm for was Johnson best displayed when he was endorsed on the fourth ballot, by a small number of delegates in a partially empty convention hall.
Johnson is one of the weakest candidates that has ever been endorsed by the Republican Party of Minnesota for governor. He is facing three other top candidates in the Republican primary election and a very divided Republican Party IN Minnesota.
The Republican Party of Minnesota has not faced a strong challenge to an endorsed candidate for statewide office in 20 years. Johnson is the endorsed candidate and it would be safe to assume he is the favorite to win the Republican primary in August. But August is a long way and things could change.
The future of the endorsement process rests on the shoulders of McFadden and Johnson. If McFadden and Johnson do not win the primary and the general election, the endorsement process is dead.
Johnson and McFadden are two different candidates. McFadden may clear the field in the primary, while Johnson will face three strong opponents. If was Johnson perceived as a strong candidate, candidates would not be filing to run against him in the primary.
Two things happen to campaigns after they win the endorsement:
- The campaigns regroup and adjust their strategy, recognizing that the endorsement is one step in the process to being elected.
- The campaign acts like every decision they have made since announcing was correct and more forward with a flawed strategy, with cocky advisors.
It remains to be seen which choice Johnson's campaign will take, but the next few weeks will be very interesting to watch. Please check back to politics.mn for additional analysis on the 2014 elections.


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Maxine Waters Reclaiming Her Time Just Became Everyone's New Summer '17 Mantra
California Congresswoman Maxine Waters puts her foot down by reclaiming her time.
After sustained criticism from outsiders, Oxygen has canceled plans to air a reality show starring the rapper Shawty Lo and his unconventional extended family, The Daily Beast reports. The program, which was to be titled All My Babies' Mamas, drew sharp criticism for a concept that was believed to promote negative stereotypes about African-American families.
In one of several online petitions started against the program, whose existence was revealed via a leaked promo, critics condemned the show's producers for exploiting the situation of Lo, who has 11 children by 10 different women.
Sabrina Lamb, author of the most popular petition — which drew over 38,000 signatures — said the show's most egregious offense would have been its impact on the children.
"This show is about more than a rapper and his girlfriends," she said in an interview with The Daily Beast. "This is a show about kids who had no choice in how they came into the world. This show sets them up to be ridiculed and made fun of. None of us should be OK with that."
In addition to petitions, the conservative group Parents Television Council had promised to boycott All My Babies' Mamas. Oxygen formally announced the cancellation of the program in a statement to the media following initial reports of the axe falling.
"As part of our development process, we have reviewed casting and decided not to move forward with the special. We will continue to develop compelling content that resonates with our young female viewers and drives the cultural conversation," said an Oxygen rep.
The special was being produced by Liz Gately and Tony DiSanto of DiGa Vision.
BET.com is your #1 source for Black celebrity news, photos, exclusive videos and all the latest in the world of hip hop and R&B music.
Click here to subscribe to our newsletter.
(Photo: Oxygen)
California Congresswoman Maxine Waters puts her foot down by reclaiming her time.
"Black women: Be fearless. Speak out for equal pay."

subset: commoncrawl


text:
- Visit
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Ceramic garniture clock painted dark blue, pink, and green with a fluted base with mermen and a goddess standing with a cherub on the top.
brass (alloy)
glass (material)
glazing (coating)
tin glaze
Garniture, Clock
Garniture, Clock
Set (.1-.3) used in Cherished Possessions 2003-2005: The Minton pottery's art director, French immigrant Léon Arnoux (1816-1902), is credited with inventing a new type of ceramic, introduced to the market in 1851. Called majolica after the Renaissance maiolica pottery that inspired it, Minton's new ceramic was a runaway success. Majolica is characterized by elaborately shaped ceramic forms glazed in a new palette of lustrous bright colors.This set was made in 1870 at the very height of majolica's popularity. It was purchased by Ogden Codman, Sr., and was part of a redecorating scheme designed to update and essentially Victorianize his colonial-era home in Lincoln, Massachusetts.
Original to Codman House (Lincoln, Mass.),
Mintons (Manufacturer)
Ball, Black & Co. (Clockmaker)
Stoke-on-Trent, England, Staffordshire; New York, NY, USA
22 1/2 x 16 x 10 1/2 (HxWxD) (inches)
Bequest of Dorothy S.F.M. Codman
New York state (United States)


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Write 52 Articles On How To Start A Business
Orçamento $30-250 USD
I need someone to write 52 articles on how to start a business. The 52 Articles will be for each state. What you will need to do is lookup how to start a business in a each state and write a how to article with steps specifically relating to each state.
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Mason City is a city in and the county seat of Cerro Gordo County, Iowa, United States. The population was 29,172 at the 2000 census. The Mason City Micropolitan Statistical Area includes all of Cerro Gordo and Worth counties.
Civil Rights Law Lawyers In Mason City Iowa
What is civil rights law?
A civil right is an enforceable right or privilege, which if interfered with by another gives rise to an action for injury. Examples of civil rights are freedom of speech, press, and assembly; the right to vote; freedom from involuntary servitude; and the right to equality in public places. Discrimination occurs when the civil rights of an individual are denied or interfered with because of their membership in a particular group or class. Statutes have been enacted to prevent discrimination based on race, sex, religion, age, previous condition of servitude, physical limitation, national origin, and in some instances sexual preference. Civil rights attorneys handle cases involving the rights of individuals to be free from unequal treatment (or discrimination) based on legally-protected characteristics such as race, gender, disability, national origin, age, sexual orientation, and religion. Civil rights cases can arise in a number of settings -- including employment, housing, lending, and education.


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All the information you need for Friday mornings final-four ball-picking
What time is it? 11am (BST)
Where is it? Nyon, Switzerland
There'll be no Premier League representation in the semi-finals of the Champions League after Leicester were knocked out by Atletico Madrid, despite a spirited second leg-display at the King Power Stadium on Tuesday night.
Instead, here's a brief glance at who's left in the hat…
Atletico Madrid (ESP)
- How they got here: Atletico Madrid 2-1 Leicester (1-0, 1-1)
- Competition best: Runners-up x 3 (1974, 2014, 2016)
Diego Simeone's warriors are into the semi-finals for the third time in four seasons, and will be desperate to lift the trophy this year after twice falling to city rivals Real Madrid during that time.
A stoic first-leg performance left Leicester with an uphill struggle for the second, not least when Saul Niguez doubled the advantage before half-time, and Atletico duly progressed despite some ruffled feathers in the second half as the Foxes threatened an unlikely comeback.
Juventus (ITA)
- How they got here: Juventus 3-0 Barcelona (3-0, 0-0)
- Competition best: Winners x 2 (1985, 1996)
Rule Juventus out at your peril. They might lack the wow factor of Real Madrid or Monaco, but Max Allegri's men set out their stall with a smashing 3-0 first-leg win over Barcelona that even the Catalan comeback kings couldn't make a dent in.
Paulo Dybala's brace inside 22 minutes did the damage in Turin, but there's also the 23-goal Gonzalo Higuain to contend with and a stingy defence that's been breached only twice in the entire competition (10 games).
Monaco (FRA)
- How they got here: Borussia Dortmund 3-6 Monaco (2-3, 1-3)
- Competition best: Runners-up (2004)
Monaco have scored three goals in each of their four knockout games so far, and took advantage of a Borussia Dortmund side perhaps distracted by recent events in the quarter-finals.
The 18-year-old Kylian Mbappe is getting folk hot under collars – he got two in the first leg and another in the return – but in reality he's just one of many vibrant youngsters who've fired the Monegasques to the Ligue 1 summit and this far in Europe. They're a terrifying proposition in full flow, but quite how they'll fare should they come up against a defence like Juventus or Atletico's is unknown. Fascinating, though.
Real Madrid
- How they got here: Bayern Munich 3-6 Real Madrid (1-2, 2-4aet)
- Competition best: Winners x 11 (1956, 1957, 1958, 1959, 1960, 1966, 1998, 2000, 2002, 2014, 2016)
The 11-time winners got the job done against Bayern Munich eventually, though required extra time and some officiating that infuriated the Barians to get the job done. Zinedine Zidane's men tore through their 10-man opposition in the additional 30 minutes, scoring three times to tip the scoreline firmly in their favour.
Cristiano Ronaldo now has 100 Champions League goals after his second-leg hat-trick, and right now it's hard to bet against him sending Real Madrid all the way once again. Should he lift the trophy again this year, the perma-tanned Portuguese will join Lionel Messi as a four-time winner.


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(A blog carnival is a collection of posts from many different bloggers about a particular topic.)
You all know that I work at two things in my parenting that seem to be in tension with one another: maintaining healthy space for myself and my needs, and being a safe, good, loving, compassionate, and respectful mama for my daughter.
You know that each of these things sometimes makes it hard for me to work on the other one. When I am feeling more need for my own space, I can feel Amy as a hindrance. When I am feeling more like an inadequate mama, I can feel myself as the hindrance to both of us. It's challenging to keep looking for the necessary, the healthy, balance.
Several of the blogs I read are written by survivors of childhood abuse. I found them, or they found me, because we both write about mental health issues.
Reading some of the things they write sometimes renews both sides of my parenting tension. When one of these survivors reminds readers to "Love your inner child," or posts a painting of a mama holding a child, and another child standing in a corner, with the caption, "Are you holding or ignoring your inner child?" it reminds me first of all to hear the whiny and defensive inner call for more me time and space as the voice of my inner child, and to respond compassionately*. It reminds me secondly to keep hearing the (sometimes unspoken, despite all her chatter) voice of my daughter calling for more together time and space, and to respond compassionately* to her as well.
It's when one is not feeling well-loved that one gets insecure, defensive, grumpy, inadequate, and so on. I need to love both of us well — me and her. And I need to drink and eat, more and more, how lavishly the Father loves both of us.
*Compassion doesn't always mean giving what is requested. But even when the answer is "no," it can be given lovingly, sympathetically, and respectfully.


text:
I just went to a spinning retreat. For the first time I went formally as a purveyor of fiber, with hand-painted wool in several colorways and a few nifty blends.
I sold all of one colorway while I was unpacking.
She also wanted me to spin it.
She also wanted me to spin a pound of totally yummy Ashland Bay wool/silk blend for her.
She took my price.
The bad news? The best wheel I've got is an Ashford.....


text:
Hi all! We're excited to announce that we are collaborating with the NFCYM to create a new venue at NCYC later this year! Check the graphic over there for more details!
announcements, catholicism, friends, good news, JesusJusticeJoy, Joy, Judaism, ministry, music, NCYC, reflection, Twenty-Third Publications, WLP
Ongoing Creation
by oddwalk • • 0 Comments
The Catechism of the Catholic Church states: 306 God is the sovereign master of his plan. But to carry it out he also makes use of his creatures' co-operation. This use is not a sign of weakness, but rather a token of almighty God's greatness and goodness. For God grants his creatures not only their…
catholicism, friends, good news, liturgy, ministry, NCCYM, NCYC, oddwalkia, travel, video
Oddwalk on Real to Reel
by oddwalk • • 0 Comments
catholicism, liturgy, ministry, NCYC, oddwalkia, pope, prayer, reflection, retreat, video
Oddwalk on CatholicTV from NCYC 2015
by oddwalk • • 0 Comments
catholicism, joke, liturgy, ministry, music, NCYC, oddwalkia, video
A Few NCYC 2015 Videos
by oddwalk • • 0 Comments
Hello Everyone! We had a marvelous time at NCYC, both making music and hanging out at the booth. Here are a few NCYC-related videos for you to enjoy.
First, an "at home" video of a new song we premiered at the NCYC comedy club, "Helping Verbs."
Next, our super-cut video of all the "Oddwalk This Way" vine videos from the booth!
And last, a video of a song we prayed with at the Friday daily mass, "Have Faith."
catholicism, liturgy, ministry, NCYC, oddwalkia, travel
Where to Find Us, NCYC 2015
by oddwalk • • 0 Comments
liturgy, NCYC, oddwalkia, prayer, quote, reflection
An Outward Sign of Christian Dignity
by oddwalk • • 0 Comments
At NCYC last month, Oddwalk had a couple conversations (in person, on Twitter) about the appropriateness of the young lay leaders of prayer, and specifically their vesting in albs and leading a communal blessing by signing themselves (as directed in many places in the Book of Blessings).
It could be that the folks we had conversations with (one adult, one youth) weren't the only ones to have concerns. The NFCYM has posted a wonderful resource explaining the catechetical, pastoral, and legal reasons that what we experienced at NCYC was exactly what was needed for that time and place.
A couple quotes to draw attention to:
The question—and answer—of proper liturgical vesture involves both clear instruction from the Church and mistaken notions from many of its members simultaneously. Frankly, it is a wrongful notion to describe a lay person leading a formal prayer service in an alb as "looking and acting like a priest." In fact, at NCYC, the youth presiders were looking and acting exactly as they should: like a lay person leading prayer.
Again, in brief, a catechesis of liturgical vesture is one that begins not with the difference of ministry or station, but on the common community shared by all in the dignity of their baptism. There is no ordination without baptism (and all the sacraments of initiation: Confirmation and Eucharist, too). There is no "priestly vestment" that does not begin first with the garment of Christian faith—laity and ordained alike—the alb with which we are all "clothed in Christ."
As a ministry especially concerned with justice and specifically the joy we can find in our having been created by God and given a Christian dignity that is indelible, we are so pleased with how the NFCYM has addressed the concerns – as too we are pleased that there are interested people, especially youth, willing to make their voice heard about matters important to them. Please take some time to read the whole document!
Edit, 12/7/14 – new link to article: http://www.ncyc.info/2013/logistics/leaders/alb.htm
baseball, catholicism, CSW, family, friends, joke, keytar, liturgy, ministry, music, NCYC, odd, oddwalkia, pets, prayer, random, technology, travel, video, weather, website
Shannon's Top Ten of 2011
by oddwalk • • 0 Comments
Well, here ends another great year for Oddwalk Ministries. We had the opportunity to bring what we do to a lot of great places: Granite City, IL – Toledo, Ohio – Mascoutah, IL – Breese, IL – Belleville, IL – Davenport, IA – Washington DC – Buffalo, NY – Fairview Heights, IL – Hazelwood, MO…
announcements, NCYC, oddwalkia, technology
iPod Nano NCYC Winner Announced
by oddwalk • • 0 Comments
Nicholas, pictured here is our big winner from the NCYC Rocking-the-Keytar photo contest. He has been contacted on facebook on how we can get him the big prize. Congratulations!
music, NCYC, oddwalkia, video
"At Your Name" at NCYC Closing Mass!
by oddwalk • • 0 Comments
Oddwalk's "At Your Name" (by Shannon) was selected as one of the communion hymns for the Closing Mass of NCYC this past Saturday night! Check out the video of it below. You'll also see our friends Paul Melley (sax) and Kate Cuddy (choir director) along the way. Great job to all involved!
NCYC, oddwalkia
Free Download – "Love" and other NCYC Info!
by oddwalk • • 0 Comments
You found the right place! Click the play button to listen to our new song, titled "Love" and released at the 2011 NCYC in Indianapolis, IN. Or, use the direct link to download to your computer or other device (if it supports that). Love (2/10/10) – A new song, free from Oddwalk Ministries! ♫ Love256.mp3…
keytar, NCYC, oddwalkia
Some Sneak Peeks of Oddwalk @ NCYC!
by oddwalk • • 0 Comments
Make a few guesses based on these pictures: go on, we dare you!
NCCYM, NCYC, oddwalkia, pOddcast, random, review, shrine, travel, video, website, YSP
Shannon's Top 15 of 2010
by oddwalk • • 0 Comments
Well, it's that time of year again. Time for me to select my top Oddblog posts for each month of 2010. In a few of the months, it was difficult to pick just one, so I didn't. Feel free to praise me, disagree, or offer your own list. Happy reading!! JANUARY While we didn't blog much in…
announcements, merchandise, music, NCYC
by oddwalk • • 0 Comments
Well, the big release is here! A new, digital download-only album! Click here for more info and for a free download!
announcements, NCYC, oddwalkia
Another Hint
by oddwalk • • 0 Comments
For that coming-soon new project. Any more guesses?
announcements, NCYC, oddwalkia
New project soon, here's a hint!
by oddwalk • • 1 Comment
family, friends, music, NCYC, video
Bless The Lord, My Soul (NCYC '09)
by oddwalk • • 0 Comments
We had the honor of leading sung prayer at two of the daily masses last fall at NCYC. Here's a video of us leading one of the communion hymns at the Thursday mass, our own setting of "Bless The Lord, My Soul (Psalm 103)" – originally written for the wedding of Shannon's sister-in-law Becca and…
friends, music, NCYC, video
"Teenagers In My Car" – the Video
by oddwalk • • 0 Comments
As promised, here's a video that is more-or-less the same set of slides we used at the NCYC 2009 Comedy Club last fall, starring our good friend (and sometimes band member) Ricky Willmann. The audio is compressed from our new CD "Alright Now." Enjoy!
ministry, music, NCYC, oddwalkia, video
These Are the Chords… (GC/DC) Video from NCYC!
by oddwalk • • 0 Comments
Well, we're finally getting around to getting some of the video from our awesome time last fall at NCYC up – and it's probably just as well that we've waited, as now we've got something to get that awful taste of a losing Olympic wager video out of our mouths… Anyway, here's out performance of…


text:
Fruity Mix!
Credits & Info
- Uploaded
- Dec 9, 2009 | 10:11 PM EST
- File Info
- Song
- 2 min 18 sec
- Score
- 3.58 / 5.00
Licensing Terms
Please contact me if you would like to use this in a project. We can discuss the details.
- Score:
- Rated 3.58 / 5 stars
- Plays & Downloads:
- 594 Plays | 67 Downloads
- Share Links:
- Genres:
- Other - Miscellaneous
- None
Author Comments
Rated 3 / 5 stars
well let's see...
To tell you the truth i'm not too sure what you're trying to get at with this song... It sounds like you made the song to learn the program ^^; A lot of it, if not all of it sounds like presets for the 3x oscillator (kick), loops (the synth), and vocals... i like that you're trying though, keep at it ^^;
unfortunately, Newgrounders are gonna pick you apart and make you implode then explode for using presets. To be honest I would rather hear bad music than repetitious loops and such, cuz i'm not hearing your raw creativity. so +6 for having an ear for smooth tones and beats. -4 for no creativity. 6/10
Keep goin' ^^
lol unfortunately i just really wanted to use the presets because i like them, so i used them. I have another 3 songs like this, just preset songs.
I've been too tired to make my own real songs. same with tonight. but i'll try as much as possible


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- Hemingway's Havana
- Chic to chic – cruising Venice to Athens in style
- Ready, action, sunset – Turtle Island, Fiji's Hollywood links
- From silo to high life – Cape Town's new luxury Silo Hotel
- Ireland – enchanting otherworld road trip
- Luxury lodge New Zealand
- Enchanted Island – Fiji
- Finding Niemeyer – Rio's great modernist architect
- Road trip around New Zealand's Northland and Rotorua
- Ten ways to get your heart hammering in Cape Town
- Ultimate South American travel by private jet
- Ashford Castle, Ireland
- The Luxe of the Irish – Belmond's new Grand Hibernian train
- Ballyfin House, Ireland – Conde Nast 2016 Best Hotel in the World
- Cape Whale Safari – South Africa
- Heaven on Earth Valley – South Africa
- Glittering palace, glittering city
- South Africa off the beaten track – charming places to stay
- Cambodia – the monk who forgot how to chant
- The Parks, Johannesburg: Three-minute guide
- In Search of Tiger – luxury Madhya Pradesh safari
- Namibia: land of sand and stone
- The Vineyard – Cape Town's lovely historic hotel
- Charleston brunches – food, food and more food
- Greenwich Village food tour – the walking picnic
- Savannah – America's next top food destination
- Vietnam's Tra Su bird sanctuary – a little piece of paradise
- New Orleans – let the good times roll!
- The Lover's House, Sa Dec, Vietnam
- The Mekong – one river, many worlds
- Pullman Rail Journeys '50s style
- Jack London State Historic Park
- My beloved Cape Town
- Biltmore – Sumptuous Dream Chateau
- Hiking the San Andreas Fault from San Francisco – a luxury hike with just a bit of terror
- Three-minute guide to Chicago
- South Africa – my best destination for a holiday
- Secret places – Wolfberg Cracks, Cederberg, South Africa
- Kotor, Montenegro – the number one city to visit for 2016
- Road Trip – Romantic cities of the US South
- Beautiful Athens – give it a chance!
- Hotel Grande Bretagne, Athens review
- Mykonos – Windmills of my Mind
- Behind the scenes tours
- Dubrovnik and Croatia's Konavle Valley
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Tag Archives: Oscar Niemeyer
Finding Niemeyer – Rio's great modernist architect
If you visit Rio, take the journey from central Rio across the Niteroi Bridge to experience the 11-kilometre Niemeyer Way. You'll be able to view the spectacular creations of a Brazilian icon, the great modernist architect Oscar Niemeyer. Here's my story … Continue reading


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Before it was an international sport, golf was only played in the hills of Scotland and on farms with burgeoning gopher infestations. Take a whack with this Groupon.
Choose from Four Options
- $10 for two tickets to the expo on August 16 ($20 value)
- $10 for two tickets to the expo on August 17 ($20 value)
- $17 for four tickets to the expo on August 16 ($40 value)
- $17 for four tickets to the expo on August 17 ($40 value)
At The Golf Resort & Taste Expo, which runs from 10 a.m. to 4 p.m. at the Riverside Convention Center, attendees can check out new golf gear and products, as well as practice their swing. In between visiting vendor booths, attendees sample wine, craft beer, and food from local restaurants. Each ticket includes four raffle tickets, three wine or craft beer tastings, and two food tastings. Attendees also get free parking. All tasting proceeds go to the California PGA and Make A Wish Foundation.
The Golf Resort & Taste Expo
The Golf Resort & Taste Expo brings visitors up to date on the world of golf with an eclectic blend of exhibits that range from demos of the latest golf equipment to travel displays on luxurious golf destinations. As expo-goers explore, washing down samples from local restaurants with similarly local wines and beers, they can even get tips from on-site golf pros on how to improve their game without hiring a caddy with mind-control powers. For a taste of the pampering they might enjoy on a golf getaway, visitors can also peruse a smattering of spa booths stocked with skincare products and details on local and destination spas.


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No Follow Vs. Follow Links- Know The Difference
Out of nearly 200 factors the search engine consider for ranking a website in SERPs, Backlinks are one of them.Read more
Out of nearly 200 factors the search engine consider for ranking a website in SERPs, Backlinks are one of them.Read more
Maintaining continuous traffic on a website or blog is not easy if you are not expanding your research to findRead more
The success of SEO campaigns depends upon the research work done by SEO experts and research work never stops. InRead more
Know all about XML sitemap, follow SEO best practices. When it comes to XML sitemap creation, we search for sitemapRead more
While conducting my research on mind mapping and online work sites, I have learned many things. Web research can beRead more
If the targeted keywords for your website have high competition, then you need to use best Off page SEO TechniquesRead more
Search engine optimization is essential, if you have a website and you want to see it on top in searchRead more
Starting a SEO campaign for your website? You cannot expect the success of SEO campaign without keywords. In this articleRead more
Evolution of different Google Algorithms like Panda, Penguin, Hummingbird, and Rankbrain has set parameters for business owners and marketers. YouRead more
Warm welcome to all the readers, I hope my articles are helping you people to understand the concept of SEO.Read more


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Join us for English Conversation on these dates. Everyone is welcome. All ages, all levels. Admission is free. We are providing an opportuntiy to meet native English speakers and give you an opportuntiy to practice and grow in your speaking abilities. We meet on the 1st and 3rd Tuesday of each month.
Next meetings:
Join us for a fun and games night on the 5th Tuesday, November 29th, 7:00-8:30pm!
December 6th, 7:00-8:30pm
Merry Christmas and Happy New Year!
We will break for the holidays until mid-January. Check back for next years dates and information about the meetings!
English for Life
Let's Speak English Together
You can find out more about the place we are meeting on our Facebook Page below.


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So my royal radar first detected Lupita when she won the Academy Award for Best supporting actress for her role as Patsy in 12 Years a slave.
The reason for this post though is I am in extreme awww and admiration of her beauty and that it has been recognised internationally. People's Magazine dubbed her with the title of "The Most Beautiful" in 2014. She was the first Kenyan Actress to win an Academy Award.
Not many words in this post. This post has various pictures admiring this beautiful woman!


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Using Solr or Lucene
Sitecore supports both Lucene and Solr search engines. The search engines are used for searching in the content databases, as well as for searching in a number of operational databases that Sitecore uses for collecting analytics data, test data, and so forth.
The search engines that are used for these two different kinds of databases do not have to be the same instance of either Lucene or Solr, and they do not even have to both be either Lucene or Solr.
When visitors search for content, they use a search engine. Therefore, this search engine must be available from the Internet. On the other hand, the search engine that Sitecore uses for the operational databases does not have to be available from the Internet.
In most situations, you have a choice between using Solr or Lucene.
There is one situation where you cannot choose between search engines, but must use Solr. If the operational indexes are on a different server than the server that hosts the services and interfaces that access these indexes, you must always use Solr. All these services depend on search for the data they need. Solr supports calls over HTTP(S), whereas calls to a Lucene index must be made from the same machine that hosts the index itself.
The general reasons for using Solr instead of Lucene are:
- When you need to index large numbers of items (50,000 and up), Solr performs better.
- Solr is more robust. If your site depends on search as the primary interface, consider using Solr.
- If you use multiple content delivery servers (or plan to do so later), use Solr. Solr works automatically in such an environment. You could use Lucene, but you have to make sure that indexes are synchronized across servers yourself.
You should therefore use Solr if you plan to scale your site (have a distributed setup with multiple servers).
You can move from Lucene to Solr. The LINQ queries remain the same, but there are differences in configuration and so forth that you need to address. You will also have to rebuild indexes. The move is possible, but it is not a trivial task.
If you do move from Lucene to Solr, be aware that Lucene and Solr score search results in slightly different ways (which can look like there is something wrong unless you know this).
You can mix Lucene and Solr, and, for example, use Solr for xDB and Lucene for content search at the same time. If an index is small, it is much easier to manage as a Lucene index because there is little to no overhead to set it up.
In most cases, though, it is simpler to move everything to Solr once you need to use Solr for the operational databases.


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Electrons flowing like liquid in graphene start a new wave of physics
A new understanding of the physics of conductive materials has been uncovered by scientists observing the unusual movement of electrons in graphene.
A new understanding of the physics of conductive materials has been uncovered by scientists observing the unusual movement of electrons in graphene.
The rapid development of wearable technology has received another boost from a new development using graphene for printed electronic devices.
Two-dimensional materials such as graphene may only be one or two atoms thick but they are poised to power flexible electronics, revolutionise composites and even clean our water.
The rapidly developing science and technology of graphene and atomically-thin materials has taken another step forward with new research from The University of Manchester.
Graphene could help reduce the energy cost of producing heavy water and decontamination in nuclear power plants by over one hundred times compared with current technologies, University of Manchester research indicates.
New research demonstrates the real-world potential of providing clean drinking water for millions of people who struggle to access adequate clean water sources.
Scientists at The University of Manchester have 're-discovered' a material, which could make the construction of 2D van der Waals heterostructures easier to build.
Stable, concentrated and inkjet-printable water-based 2D crystal inks developed which could be used in packaging, counterfeiting and biomedical applications.
Science and fashion have been brought together to create the world's most technically advanced dress, the intu Little Black Graphene Dress.
An ultralight high-performance mechanical watch made with graphene is unveiled today (16 January 2017) in Geneva at the Salon International De La Haute Horlogerie thanks to a unique collaboration.
A unique portrait gallery has been unveiled at the National Graphene Institute (NGI
World-first graphene innovation could be used for applications in medical devices and diagnostics
Graphene used as a 'paper' on which to 'write' chemical patterns thousand times narrower than human hair.
Two-dimensional materials could bring smaller, faster computer circuits to realisation.
Following a decade of intensive research into graphene and two-dimensional materials a new semiconductor material shows potential for the future of super-fast electronics.
The Sir Henry Royce Institute for Advanced Materials has appointed a leading materials scientist and engineer as Chief Executive.
Manchester's revolutionary 2D material
the story of graphene and its applications
with The University and the National Graphene Institute
the latest research into graphene and other 2D materials
the story of graphene and its applications
with The University and the National Graphene Institute
the latest research into graphene and other 2D materials
Imagine clean drinking water for millions in developing countries. The development of graphene-based membranes at The University of Manchester brings that possibility closer.
Graphene oxide membranes are capable of forming a perfect barrier when dealing with liquids and gasses. They can effectively separate organic solvent from water and remove water from a gas mixture to an exceptional level. They have even been proved to stop helium, the hardest gas to block.
The simplicity of the technique and the sophistication of the membranes developed at The University of Manchester means the scope for potential applications is widening quickly, whilst each day of research brings with it new ideas.
We are currently looking at how graphene membranes can be used for water filtration, gas separation and desalination projects.
A single layer of atoms that can act as a perfect barrier has the potential to open up vast new markets and revolutionise countless industrial processes.
Using graphene coatings on food and pharmaceutical packaging can stop the transfer of water and oxygen keeping food and perishable goods fresher for longer. The removal of harmful carbon dioxide released into the atmosphere by power stations is not currently done on any scale, graphene membranes could change that.
The versatile use of graphene oxide membranes could have benefits for huge areas of industry, and the University is working with a number of commercial partners, to turn research into viable commercial applications.
The University of Manchester is dedicated to focusing on the research and development of graphene and graphene oxide membranes in collaboration with commercial partners. Nowhere else is there such a breadth of expertise looking at this potentially vast area of advancement for countless industries.


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Limestone College animal science
Think about what career is best suited for you, and where you want to study. Request more information now.
Think about what career is best suited for you, and where you want to study. Request more information now.
Think about what career is best suited for you, and where you want to study. Request more information now.
Get the facts about Limestone College animal science, and registering for elective seminars. Which college degrees give you the best chances of finding employment after graduation? Seek out accredited nursing programs for the best training. Given a brief hospital internship or prior work experience, you can expect a great return on your medical education. Concentrating on Limestone College animal science, for example, you may gain an advantage in job recruiting on-campus. Check with the vet tech department for course registration deadlines, and veterinary program requirements. Please use the form above to request admissions info for Limestone College.
Veterinary assistants and laboratory animal caretakers look after animals in laboratories, animal hospitals, and clinics. Veterinary technologists and technicians perform medical tests under the supervision of a licensed veterinarian to assist in diagnosing the injuries and illnesses of animals. Veterinary technicians must complete an associates program in veterinary technology, while veterinary technologists require a 4-year bachelors degree. The median annual wage for veterinary technologists and technicians was $32,800 in May 2017. Employment opportunities are projected to grow 20% over the coming decade, much faster than the average for all medical occupations.
In 2017, there were 231 veterinary technology programs accredited by the American Veterinary Medical Association (AVMA). Most states require veterinary technicians to pass the Veterinary Technician National Examination (VTNE), offered by the American Association of Veterinary State Boards. For technologists seeking work in a research facility, the American Association for Laboratory Animal Science (AALAS) offers the following certifications: Laboratory Animal Technician (LAT) and Laboratory Animal Technologist (LATG). To become certified, candidates must have work experience in a laboratory animal facility and pass the AALAS examination. Beyond major requirements within the vet tech department, you may consider Rappahannock Community College nurse assistant program as a complementary elective to your primary course of study.
RN or LPN (Registered / Licensed Practical Nurse)
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A group of Southampton scientists have discovered a star in the closest known orbit to what is believed to be a black hole.
Astronomers, including a team from the University of Southampton, have found evidence that the star whips around a black hole about twice an hour. It is thought this may be the tightest orbital dance ever witnessed for a likely black hole and a companion star.
This discovery was made using NASA's Chandra X-ray Observatory as well as NASA's NuSTAR and CSIRO's Australia Telescope Compact Array (ATCA).
The close-in stellar couple – known as a binary – is in the globular cluster 47 Tucanae, a dense cluster of stars in our galaxy about 14,800 light years from Earth.
While astronomers have observed it for many years, it wasn't until 2015 that radio revealed the pair was likely to contain a black hole.
Professor of Astrophysics, at the University of Southampton, which found that the X9 system was an accreting compact object in a close binary system.
Professor Knigge, professor of astrophysics at the University of Southampton, who is one of the authors on the paper, said: "This is an extremely exciting result, because this may be the first black hole discovered to date that is fed by a white dwarf companion in this kind of ultra-compact configuration."
Although the white dwarf does not appear to be in danger of falling in or being torn apart by the black hole, its fate remains uncertain.
First author Arash Bahramian, of the University of Alberta in Edmonton, Canada, and Michigan State University in East Lansing, said: "This white dwarf is so close to the black hole that material is being pulled away from the star and dumped onto a disk of matter around the black hole before falling in.
"Luckily for this star, we don't think it will follow this path into oblivion, but instead will stay in orbit."
A copy of the research paper is available at https://academic.oup.com/mnras/article/467/2/2199/3052451/The-ultracompact-nature-of-the-black-hole?searchresult=1.


text: Writer Madeleine Thein will be a guest at the upcoming Perth Writers Festival. She is the author of three novels and her latest, Do not say we have nothing, was long-listed for the Man Booker Prize. The novel follows the lives of three musicians and their families through tumultuous events in China's modern history. You can hear this delightful and informative interview Madeliene Thein recorded with Canada's CBC Radio.


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For my birthday, my mum offered me my grandmother's sewing machine. It's not a modern one, but I love Singer sewing machine quality (the ones that are from the 60' - 80'). Nowadays they are made in China and quality is not as good as before.
I could find a video on our national archives (INA):
commenter cet article


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LA Forum event co-coordinator (with Patricia Bacalao, Jennifer Bonner, Victoria Camblin, Wendy Gilmartin, and Roberto Sheinberg) Event photography by Monica Nouwens *** "We offer LA as a case study in the designed domestic and urban environments that should give us clues about America at large. The cleansing effects and the nourishing and communal aspects of […]
Exhibition Coordinator Julius Shulman (October 10, 1910 – July 15, 2009) The Kaufmann House. Palm Springs, CA. June 2003 *** The 2017 Julius Shulman Institute Excellence in Photography winner, Todd Eberle, brings the human into the architectural image. He insists that a portrait of the built environment is a portrait of its authors and vice […]
View Original Art Papers, Special Architecture and Design Issue, Spring 2017 The emblematic work of "Doug Aitken: Electric Earth," the comprehensive survey of the LA native's films, sculptures, prints, and multimedia productions curated by MOCA director Philippe Vergne, is a pool. Excavated from the concrete and dirt foundation of the rear northeast corner of the […]
View Original Architecture for Sale, Spring 2017 Nestled beneath ancient oaks, the low, white ranch house with the cement tile roof does not broadcast its architectural import. Yet this unpretentious residence, set well back from the road in a guard-gated community on the edge of the San Fernando Valley is an essential key to the […]
Talking LA streets with Johanna Blakley, Bill Ferehawk and David Hartwell, Naomi Iwasaki, David Ulin, and Andrew Wilcox for LA Forum's 2016 summer exhibition, "Median."
Reports on, reviews of, and conversations about "Reporting from the Front," the 2016 Biennale di Architettura di Venezia.
Conversations about (Italian) things with Ilaria Mazzoleni.
A review of Design Matters gallery's "Xenotypes" exhibition.
A review of Studio Pali Fekete Architect's Caverhill House.
An exhibition of Wayne Thom's architectural photographs, co-curated with Nicholas Olsberg.
A review of Barbara Bestor's Blackbirds housing development.
Short stories of wallpaper.
A review of Pierre Koenig's renovated Henbest House.
Digital fabrication and wood and metal shop facility design and operations.
A study in facilitating individual ideation and structuring architectural research.
A counter to ghosts (minds without bodies) and zombies (bodies without minds).
Thoughts towards rethinking architecture and design education.
Curriculum development for the professional and post-professional graduate programs at Woodbury School of Architecture.
Woodbury School of Architecture's advanced design software and technology workshops.
Info-graphic design and research for Kyong Park's exhibition at the Museo de Arte Contemporáneo de Castilla y León (MUSAC).
The Political Equator I and II exhibition and event coordination and design for estudio Teddy Cruz.
Info-graphic design and research for estudio Teddy Cruz contribution to the 3rd International Architecture Biennale Rotterdam.
What is architecture in a world turned upside down? Master of Architecture thesis at Rice University.


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Upon encounter with antigen, CD4+ T cells differentiate into effector Th subsets with distinctive functions that are related to their unique cytokine profiles and anatomical locations. One of the most important Th functions is to provide signals to developing B cells that induce specific and appropriate antibody responses. The major CD4+ T cell subset that helps B cells is the T follicular helper (TFH) cell, whose expression of the chemokine receptor CXCR5 [chemokine (C–X–C motif) receptor 5] serves to localize this cell to developing germinal centers (GCs) where it provides instructive signals leading to Ig class switching and somatic mutation. TFH cells produce high levels of IL-21, a cytokine that is critical for GC formation and also for the generation of TFH cells. Although TFH cells have been found to produce cytokines characteristic of other Th subsets, they represent a distinct lineage whose development is driven by the transcription factor B-cell CLL lymphoma-6 (BCL6). Consistent with their critical role in the generation of antibody responses, dysregulated TFH function has been associated with the development of systemic autoimmunity. Here, we review the role of IL-21 in the regulation of normal TFH development and function as well as in progression of autoimmune responses.
Specific CD4+ T cell effector responses can be delegated to distinct subsets characterized as Th1, Th2, Th17 or regulatory T cell (Treg) cells, with the development of each of these subsets being driven, respectively, by the master lineage-specific transcription factors T-bet [now also denoted as T-box 21 (TBX21)], GATA binding protein 3 (GATA-3), retinoid-related orphan receptor γt (RORγt) or forkhead box protein P3 (FOXP3) (1). T-cell-dependent antibody production is a critical component of the normal immune response, and Th2 cells were originally believed to be the predominant source of B cell help because of their production of IL-4, a cytokine known to be involved in B cell proliferation as well as Ig class switching (1).
Subsequently, IL-21 was identified as a Th-derived, type I, four-α-helical bundle cytokine that was critical for plasma cell generation as well as isotype switching (2) and normal Ig production (3), consistent with IL-21 being a Th2-specific cytokine (4); however, other data indicated that IL-21 had Th1-like properties as well (5).
More recently it became clear that the CD4+ T cells involved in germinal center (GC) formation and function—denoted T follicular helper cells (TFH cells)—were distinct from any of these previously identified subsets. These TFH cells expressed high levels of the chemokine receptor CXCR5 [chemokine (C–X–C motif) receptor 5], allowing them to home to and be retained by the lymphoid follicle, where contact with antigen-primed B cells led to B cell proliferation, isotype switching and somatic mutation of the Ig repertoire (6, 7). Gene microarray analysis revealed that follicle-localized CXCR5+ Th cells had a very distinctive transcriptional profile that distinguished these cells from Th1 or Th2 cells, with high-level IL-21 and B-cell CLL lymphoma-6 (BCL6) messenger RNAs (mRNAs) (5), both of which are now considered hallmarks of TFH cells (6).
IL-21 is a type I cytokine that signals via a specific receptor protein, IL-21R (8, 9), and the common cytokine receptor γ chain, γc, which is shared by the receptors for IL-2, IL-4, IL-7, IL-9, IL-15 and IL-21 (10); γc is mutated in humans with X-linked SCID (11). IL-21 signals in part via STAT3 (signal transducer and activator of transcription 3) (12), with actions on a wide range of lineages, including T cells, B cells, NK cells and dendritic cells (10). Specifically, IL-21 can promote the expansion of CD8+ T cells, is critical for normal Ig production by B cells, can inhibit dendritic cell function and, interestingly, can be pro-apoptotic for B cells and NK cells (10). Whereas IL-21 was first identified as a cytokine produced by activated peripheral blood T cells (9), it is now known that it can be produced by a range of differentiated Th populations (10) as well as by NKT cells (13).
In this review, we discuss the role of IL-21 in the generation of TFH cells as well as in the functional interaction of these cells with B cells within the GC. The relationship between TFH and other Th subsets will also be discussed, as more evidence mounts in support of flexibility of cytokine profiles within the TFH cells. In addition, the role played by IL-21 in the interaction between the TFH master transcription factor BCL6 and other lineage-specific transcription factors will be discussed. Finally, elevated levels of IL-21 and TFH-specific surface molecules have been implicated in the development of systemic autoimmune responses, and the mechanisms for disease development will be addressed.
Early molecular profiling of human TFH cells revealed that although a large number of transcripts were shared by TFH, Th1 and Th2 effector cells, a subset of genes were preferentially expressed by TFH cells, including those encoding CXCR5, IL-21, BCL6 and ICOS (inducible co-stimulatory molecule) (5). Although these genes were transiently expressed to some degree by activated Th1 or Th2 cells, the spatial and temporal expression pattern of these proteins in TFH cells was coincident with their functions. Interaction between CXCR5 and chemokine (C–X–C motif) ligand 13 (CXCL13), which is produced in the follicle, was required for the localization of TFH to the GC (14), whereas ICOS co-stimulatory interactions with inducible co-stimulatory molecule ligand (ICOSL) on B cells were found to be important for GC development (15). BCL6 was already known to be highly expressed within the GC and to be required for GC formation (16). Finally, accumulating evidence has revealed that IL-21 is a key determinant of B-cell differentiation (2, 3, 10).
Both in vivo and in vitro evidence demonstrates that IL-21 is a T-cell-derived cytokine that is very important for B-cell proliferation and differentiation (10). Mice that constitutively expressed IL-21 were found to have higher levels of plasma cells as well as higher levels of serum Igs (2). In vitro stimulation of both murine and human B cells with IL-21 induced the plasma-cell-associated transcription factor BLIMP1 (B-lymphocyte-induced maturation protein 1) [now termed PR domain containing 1, with ZNF domain (PRDM1)] and subsequent plasma cell differentiation as well as the accumulation of isotype-switched Igs (2, 17). Interestingly, Ozaki et al. also showed that IL-21 is a potent inducer of BCL6 (2), a transcription factor that negatively regulates expression of BLIMP1, just as BLIMP1 represses BCL6 (18), suggesting that these two transcription factors are induced in distinct populations of cells.
When a population of CXCR5+ tonsillar TFH cells was cultured with naive human B cells, the accumulation of Ig-secreting B cells was decreased dramatically if IL-21 action was blocked, demonstrating that TFH secretion of IL-21 was critical for the differentiation of naive B cells (19). Interestingly, in both murine and human in vitro systems, IL-4 was shown to antagonize the actions of IL-21 on plasma cell differentiation (2, 19), even though analysis of Il21r or Il4 single-knockout (KO) mice and Il21r plus Il4 double-KO mice revealed that cooperative actions of these cytokines were required for Ig production (2). In addition, even though IL-21 is a potent inducer of IL-10 (20), IL-21 was found to be much more potent than IL-10 for the induction of Ig secretion from both naive and memory human B cells in vitro, suggesting that IL-21 plays a major role in both primary and memory responses to T-cell-dependent antigens (19).
Although microarray analysis and hierarchical clustering revealed that the overall transcriptional profile of TFH cells was distinct from that of Th17 cells as well as those of Th1 or Th2 cells (21), both TFH and Th17 subsets share high-level expression of IL-21 (21). IL-21 was found to be required in part for the in vitro differentiation of Th17 cells, but it was not necessary for their in vivo differentiation (22). These data suggested certain similarities but also important differences between TFH cells and Th17 cells, worthy of further investigation.
GC development is impaired in mice deficient for IL-21 signaling (3). As producers of high levels of IL-21, TFH cells are important regulators of the GC reaction because of their close association with CXCR5+ B cells localized to the follicle that undergo differentiation in response to both soluble and cell-mediated signals and produce high-affinity Ig (6, 7) (Fig. 1).
A recent study investigated whether this IL-21 requirement for the GC reaction reflected the action of IL-21 on either the B cells or the TFH cells (23). Immunization of IL-21-KO mice with a T-cell-dependent antigen showed that CXCR5 surface expression on CD4+ T cells was greatly reduced in the absence of IL-21, suggesting that IL-21 has an autocrine role for proper TFH development. Consistent with this, IL-21R expression was significantly higher on CXCR5+CD4+ than on CXCR5−CD4+ T cells (23). Adoptive transfer of wild-type (WT) CD4+ T cells into Il21r-KO recipients followed by immunization rescued GC formation and partially rescued Ig production. However, the transfer of WT B cells into Il21r-KO mice could not rescue Ig production, indicating that the defect in these mice was intrinsic to the CD4+ T cells (23).
Surface expression of ICOS is required for efficient TFH development, as ICOS-KO mice have reduced numbers of CXCR5+ CD4 T cells (24). In addition, ICOSL-deficient mice had reduced expression of IL-21 (21). Specific deletion of ICOSL in B cells resulted in a significant reduction in both the number of CXCR5+CD4+ T cells as well as the level of IL-21 after immunization, demonstrating that the interaction of ICOS on TFH cells with ICOSL on GC B cells is required for maximal IL-21 production (21).
Analogous to TFH cells, Th17 cells also express ICOS on their cell surface. An investigation of the requirement of ICOS for TFH and Th17 development revealed that although ICOS was required for GC formation, ICOS was not required for Th17 differentiation but instead was required for the maximal expansion of both Th17 cells and TFH cells (25). TFH and Th17 cells were also found to share high expression of the transcription factor c-Maf, and deletion of c-Maf led to reduced numbers of both TFH and Th17 cells. This was related to the direct regulation of IL-21 transcription by c-Maf subsequent to the induction of c-Maf by ICOS–ICOSL interaction (25, 26).
Although it is clear that TFH cells are critical for directing the development of an antibody response by GC B cells, the above studies (21, 23) reported that IL-21 acts primarily in an autocrine manner on the TFH population, even though it is well known that IL-21 receptors are expressed on B cells and B cells can also respond to this cytokine by undergoing differentiation and producing Ig (2, 3, 10). Interestingly, gene microarray analysis suggested that TFH cells lacked expression of most cytokines or transcription factors associated with the Th1, Th2 or Th17 subsets (5, 21), including IL-4 and IFN-γ, making it unclear how and where these cytokines could influence B-cell Ig isotype switching if they were not produced by TFH cells. Importantly, however, in vitro Th activity for B-cell Ig production has also been detected in Th1, Th2 and Th17 polarized populations, indicating that this helper activity is not specific only to TFH populations (27).
Several reports have challenged the notion that TFH cells lack the expression of cytokines associated with these other Th subsets, including three studies that used infection with helminths that elicit strong Th2 responses (28–30).
The first study monitored IL-4 expression by employing a 'dual-reporter' mouse model in which IL-4 transcription and protein production could be distinguished. After infection with Schistosoma mansoni, the majority of IL-4-producing cells in lymph node and spleen expressed the TFH markers CXCR5, ICOS and programmed death-1 (PD-1), although the IL-4-producing cells within liver granulomas did not express these markers (28). These IL-4-producing TFH cells expressed amounts of IL-4 and GATA-3 transcripts that were similar to the level found in Th2 cells that did not express TFH markers and also produced the high levels of BCL6 characteristic of TFH cells. Experiments in which CXCR5−PD-1− cells that expressed green fluorescent protein-labeled IL-4 (this marks IL-4 protein in this dual-reporter system) were transferred into naive mice and then antigen challenged demonstrated that 20% of these cells could become CXCR5+PD-1+ in vivo, confirming that at least a minority of Th2 cells can develop into TFH cells (28).
Consistent with this, the second study reported that IL-4-producing TFH cells were present in the mesenteric lymph nodes after infection with Heligmosomoides polygyrus. Using the IL-4 transcription/protein dual-reporter mice described above, CD4+ T cells that were committed to the Th2 lineage were found throughout the follicle, but those Th2 cells that produced IL-4 protein were found only near B cells in the GC region (29). These IL-4 protein-producing cells expressed high levels of CXCR5, ICOS, PD-1, IL-21 and BCL6, as is typical of TFH cells.
The third study elegantly addressed the role of TFH cytokine production in isotype switching and somatic mutation. Here, conjugates consisting of B cells plus T cells were isolated from GCs of IL-4/IFNγ dual-reporter mice that had been infected with Leishmania major (30). These T cells expressed high levels of IL-21, BCL6 and CXCR5 characteristic of TFH cells. B-cell–T-cell conjugates with IL-4-expressing cells were shown to contain IgG1 transcripts, whereas conjugates that contained IFNγ-expressing cells contained mainly IgG2a transcripts, demonstrating that the specific cytokine produced by the TFH was critical in the regulation of isotype switching in B cells. Purified IL-4-producing cells were analyzed for IL-21 production by enzyme-linked immunosorbent spot, and IL-4+ TFH cells from lymph nodes produced significantly higher amounts of IL-21 than did IL-4-producing cells from lungs. The IL-4-producing cells from the lungs but not the IL-4-producing TFH from the GC could function as classical Th2 cells in that they could elicit eosinophil recruitment when transferred to IL-4-deficient mice, suggesting important differences between these populations (30).
In addition to evidence supporting the existence of TFH cells expressing either IL-4 or IFNγ, studies in mice prone to autoimmune lupus revealed the existence of TFH cells that produce both IL-17 and IL-21 (31).
The most surprising example of lineage switching involves the conversion of FOXP3+ Treg cells to TFH cells in the Peyer's patches of the gut, where GCs are critical for the production of IgA (32). When FOXP3+ cells were transferred into T-cell-deficient CD3ε-KO mice, 80% of these were found to down-regulate FOXP3 expression, migrate into the B-cell follicles of Peyer's patches and express high levels of IL-21 and BCL6 (32). Although FOXP3 down-regulation was not dependent on B cells as it could occur in B-cell-deficient mice, the acquisition of CXCR5, PD-1 and IL-21 required interaction with B cells in Peyer's patches (32).
IL-21 in combination with transforming growth factor-β1 (TGFβ1) produced by TFH cells can also contribute to the differentiation of IgA-secreting plasmablasts in the gut (33). In this scenario, the combination of TGFβ1 with IL-21 up-regulated chemokine (C–C motif) receptor 10 (CCR10) and down-regulated CXCR5, thus allowing migration of the B cells out of the GC and toward the mucosal surface.
Collectively, the above studies show that TFH cells can produce IL-4, IFNγ or IL-17 and that these cells are potentially derived from a range of lineages, including Th1, Th2, Th17 or Treg cells (Fig. 2).
Although early gene expression analysis established a correlation between BCL6 transcription factor expression and TFH cells, only recently have experimental approaches verified the causal nature of this expression. Consistent with the reduced TFH cell numbers in Il21r-KO mice and with the original demonstration by Ozaki et al. (2) in 2004 that IL-21 is a potent inducer of BCL6, Il21-KO mice showed diminished expression of BCL6, and either IL-6 or IL-21 could induce BCL6 expression in naive CD4+ T cells (34).
While over-expression of BCL6 was shown to up-regulate endogenous BCL6, IL-21R, IL6R and CXCR5 mRNA, it also inhibited IL-17 expression by blocking the functional activity of RORγt without affecting RORγt mRNA expression (34). BCL6 over-expression also can inhibit the expression of Th1-associated genes and Th2-associated genes (34). Experiments employing mixed bone marrow chimeras showed that BCL6 expression was required in both T and B cells for normal GC formation.
BCL6 repression of the development of other Th lineages involves direct binding and suppression of the promoters of the Tbx21 and Rorc genes in TFH cells (34). BCL6 can also repress expression of microRNAs that otherwise suppress expression of TFH-specific genes such as those encoding CXCR5 and PD-1 (35). Thus, over-expression of BCL6 led to a global down-regulation of microRNAs that targeted sites in the 3′ untranslated regions of CXCR5 and PD-1 mRNAs, thereby promoting expression of the TFH program (35).
Constitutive BCL6 expression induced expression of a panel of TFH markers but it also inhibited the expression of BLIMP1 (36), known to be an inhibitor of BCL6 function (18). Over-expression of BLIMP1 in CD4+ T cells significantly reduced the number of TFH cells, without effecting the expression of Th2-specific, Th17-specific or Treg-specific transcription factors (36). Thus, just as BCL6 and BLIMP1 can function as mutually inhibitory cross-regulators of B cell differentiation pathways (18, 37), so can they regulate the CD4 T-cell differentiation pathway, amplifying the TFH responses that will then induce strong BCL6-dependent GC reactions. It is interesting that IL-21 is a potent inducer of both BLIMP1 and BCL6 (2), but because of their cross-inhibition, presumably one of these factors will dominate within a particular cell.
GCs are a critical site for selection of appropriate antibody specificities and TFH cells play an important role in the regulation of autoantibody production, as shown by the systemic autoimmune responses that result from over-expression of TFH signaling proteins such as ICOS or IL-21.
The first suggestion of a connection of IL-21 to autoimmune disease came from the BXSB-Yaa mouse model of systemic lupus erythematosus, which was found to have elevated levels of IL-21 mRNA and serum protein (2) that temporally correlated with development of disease. In this model, IL-21 signaling was shown to be essential to the development of the disease phenotype, as when the BXSB-Yaa mice were crossed onto the Il21r-KO background, there was no hypergammaglobulinemia, autoantibody production or renal disease (38). Interestingly, these BXSB-Yaa/Il21r-KO mice had greatly reduced numbers of CXCR5+ICOS+CD4+ T cells, and the excessive IL-21 production did not derive from this population of conventional TFH cells, but rather from an extrafollicular population of ICOS+ CD4+ T cells (38).
Mice homozygous for the sanroque allele of Roquin also develop a lupus-like disease accompanied by the accumulation of excessive numbers of both GCs and TFH cells with high levels of ICOS and IL-21 expression (39), and lupus-like symptoms were dependent on enhanced GC formation as they could be reduced by deletion of even one allele of the BCL6 (40). Interestingly, however, TFH formation in this disease may be more dependent on ICOS than IL-21 (40).
In the MRLlpr mouse, which also develops a lupus-like disease, an extrafollicular population of ICOShiCD4+ T cells that have down-regulated P-selectin glycoprotein ligand 1 (PSGL-1) were the primary source for IL-21 production and subsequent extrafollicular development of IgG+ plasmablasts (41). These extrafollicular PSGL-1lo CD4+ cells also occurred at a high frequency in several other autoimmune models. In contrast to the originally defined TFH population, these PSGL-1lo CD4+ T cells also secreted IL-4 and IFNγ, which could instruct appropriate isotype switching in this extrafollicular setting (41). The relationship between these extrafollicular CD4+ T cells and the TFH population remains to be determined.
It is important to recognize that IL-21 can contribute to other autoimmune diseases as well, ostensibly by B-cell-independent mechanisms. For example, in the non-obese diabetic (NOD) mouse model of type I diabetes, disease no longer develops when the NOD mouse is crossed to the Il21r-KO background (42, 43). Thus, whereas the relationship of IL-21 to TFH is very important, one must be cognizant that it may not dominate all types of autoimmune responses.
TFH cells are now recognized as a distinct helper subset whose differentiation requires the transcription factor BCL6, leads to a GC-localized population of cells that are critical in the development of a strong Ig response. Naive TFH cells produce abundant IL-21, which then acts as an autocrine factor for the functional activity of these cells. In addition, it is now clear that TFH also have the capacity to produce cytokines characteristic of Th1, Th2 and Th17 cells, emphasizing the developmental and functional plasticity of all these subsets. Future studies are needed to further unravel mechanisms for controlling the production and activation of TFH cells, as these cells and the IL-21 they produce play important roles in a number of systemic autoimmune diseases.
Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health.
We thank Drs Irina Rochman, Edwin Wan and Jian-Xin Lin, National Heart, Lung and Blood Institute, National Institutes of Health for critical comments.
Conflict of Interest: The authors are inventors on patents and patent applications related to IL-21.
PubMed Central Canada is a service of the Canadian Institutes of Health Research (CIHR) working in partnership with the National Research Council's national science library in cooperation with the National Center for Biotechnology Information at the U.S. National Library of Medicine(NCBI/NLM). It includes content provided to the PubMed Central International archive by participating publishers.


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|In the year 2379, a Deep Space Station was designed to house the vampires of Earth. Now under the command of Captain Jadzia Dax with the help of The dashing Field Admiral Nick Knight and his wife the stunning Captain Athena Zoden Knight these brave souls team up to fight the perils of deep space. Deep Space Arc was named after Nick's Patron Saint. Members are encouaged to write fan fiction using Star Trek or Forever Knight characters as well as ones they make up. We promote non censorship of our posts. We just ask everyone respects everyone's rights.
|Admiral Nick Knight
|Commodore Athena Knight
|Captain Jim Sheriden
|USS Blade
|USS Crusador - 2382
|Captain Soleta of the USS Trident
|Nexus Fleet Field Admiral
|Lt. Cmdr B'elanna Torres
|Lt. Jennifer Waverly
|Commissioner Mina Harker
|Commissioner Apollo
|Lt. Xaul
|Natalie Lambert
|Amina Rosewyne
|Lt. Katarina Leifson
|Rebecca Solomon
|USS Trident
|Darkness, Emperess of the Brethren Planet
|Tylanna Knight Palamas
|Lt. Prometheus
|Captain Phillip Scorpico
|Miran Scorpico
|Cadet Daphne Scorpico
|Lt. Tarly Argelian
|Dr. Celiana Scorpico
|Captain Jadzia Dax
|Deep Space Arc
|This sim is dedicated to Beth, Mickey and Anna. May they always find the peace they are looking for. We love them so much.
|Lt. Cmdr Arturos Palamas
|Lt. Stephanie Grey
|Dr. Tasha Yar
|Lt. Mark McHenry
|Major Calisto Redhawk and Commander Michael Redhawk
|The Planet of the Vampire Brethren
|Lord Kronos
|Lord Kronos and the Emperess Darkness
|Lord Kronos and the Angel Brandy
|Julietta Kroniz, the Donna of the Kroniz Family
|Sigma Iotia II
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|Jack Okmyx, Concierge
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|Lt. Cmdr Garot Troy
|This sim is dedicated to the loving memory of our departed friend who played Annika Devin. She taught us so many things and the most of all was to love one another. She was one of a kind. So in her immortal words, "I thank you kindly" for all you did for all of us.
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College GameDay Built by The Home Depot will originate from Norman, Okla., on Saturday, Oct. 27, the site of the prime-time matchup between No. 5 Notre Dame (7-0) at No. 8 Oklahoma (5-1), which will be televised nationally on ABC (8 p.m. ET). The GameDay set will be located on the South Oval lawn in front of the library.
College GameDay will air live at 9 a.m. on ESPNU and 10 a.m. on ESPN with host Chris Fowler, analysts Lee Corso, Kirk Herbstreit, Desmond Howard and David Pollack, and host/reporter Samantha Steele and Tom Rinaldi. Brent Musburger and Herbstreit will call the game with sideline reporter Heather Cox.
College GameDay will make its seventh visit to the home of the Sooners and its first since November 22, 2008. Oklahoma is 5-1 with GameDay on campus and has won the last five of those games. The lone loss came in GameDay's first visit to Norman on September 30. 1995 (Colorado won, 38-17).
Corso is 4-1 with his Sooners headgear picks (having not picked for the 1995 game). The lone time he picked against Oklahoma while in Norman was on September 29, 2001, when he went with Kansas State, which wound up falling, 38-37.


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(Pakistan) 5,000 Hindus Flee Forced Conversions, Kidnappings, Rape...
JAISALMER: In the past four years, some 5,000 Hindus may have crossed over from Pakistan, never to return. It has not been easy abandoning their homes, sometimes even their families, but they say the
By: THE_HAMMER_OF_POITIERS | Comments: 4 | Views: 10075 | Votes: 0 | Shared: 0
Leaked: Sep-10-2009 in LiveLeaks
muslims Attack Hindus In Bangladesh...
Reports began trickling out of Bangladesh this spring about an anti-Hindu violence in the heart of its capital carried out in three stages: March 30, April 17, and April 29. A community of approximate
By: THE_HAMMER_OF_POITIERS | Comments: 5 | Views: 10602 | Votes: 0 | Shared: 1
Leaked: Jul-24-2009 in News
(UK) muslims Deny Hindus Access to 'Multi-Faith Center'...
As part of their "Sewa Week" (a week for which the National Hindu Students Forum holds various service based activities, the QMW Hindu Society organized to use the University's Multi-Faith Centr
By: THE_HAMMER_OF_POITIERS | Comments: 7 | Views: 9583 | Votes: 0 | Shared: 0
Leaked: Jul-23-2009 in LiveLeaks
Hindus Told to Embrace Islam, Pay Up or Else...
MANSEHRA: Chief of the Hindu community in Battagram said on Sunday that the Taliban had threatened them to pay Jazia (tax) or accept Islam. 'It depends on you to choose between Jazia and Islam ot
By: THE_HAMMER_OF_POITIERS | Comments: 52 | Views: 11481 | Votes: 1 | Shared: 0
Leaked: Jun-29-2009 in Middle East
When I was kid of 4-5 years old, I have no idea what a muslim (or hindu) is?? When I was 8-9 yrs, I came to know that people with name pervez, asif are different, as they pray to different God... S
By: fatality09 | Comments: 11 | Views: 6187 | Votes: 0 | Shared: 1
Leaked: Jun-8-2009 in Other
Muslims killed 80 million hindus in 500 years
Mr Asim, You need to read your indian history to realize the genocide of hindus carried out by muslims invaders and kings. It was by far the worst in recorded history. Will Durant, the famous histo
By: J_D | Comments: 8 | Views: 15943 | Votes: 2 | Shared: 284
Leaked: Mar-13-2009 in Afghanistan, Other
This is how Muslims treated innocent Hindus in Kashmir (Religion of peace)
This is how Muslim rulers treated Hindus of Kashmir after illegally invading it. Kashmir was a part of Bharatvarsh/Aryavrata ie present India. Kashmir belongs to the union of India and not to an artif
By: fatality09 | Comments: 9 | Views: 7640 | Votes: 0 | Shared: 1
Leaked: Mar-6-2009 in Other
India Airliner Alleged To Be Involved In Smuggling Hindus Into Canada
- TORONTO,CANADA: Streams of Hindus with fake & doctored hospitals are coming into Canada and asking for refugee status once here and canadian immigration officials are blaming Indian Airliners for
By: Rubicon_Cube | Comments: 13 | Views: 4957 | Votes: 0 | Shared: 0
Leaked: Feb-3-2009 in News
168 Hindus Killed in Stampede Resulting from Bomb Threat...
JODHPUR, India - Thousands of pilgrims panicked by false rumors of a bomb stampeded at a Hindu temple in western India on Tuesday, killing at least 168 people in the crush to escape. Television fo
By: Charles_Martel | Comments: 25 | Views: 9806 | Votes: 0 | Shared: 0
Leaked: Sep-30-2008 in Other
Report Confirms 59 Hindus Burned Alive.
First part of the Nanavati Commission report investigating into the Godhra train carnage was tabled in the Gujarat Assembly on the first day of it's monsoon session. In 2002, 59 Hindus including wom
By: Charles_Martel | Comments: 9 | Views: 9676 | Votes: 0 | Shared: 0
Leaked: Sep-25-2008 in Other
Muslims, Hindus Join Hands to Help Bomb Blast Victims
NEW DELHI/JAIPUR/PUNE, 15 May 2008 � When Indian television news broadcasts appealed for blood donors yesterday, a day after 80 people were killed in bomb blasts in India�s Jaipur city, Yaseef Khan ru
By: theblue8 | Comments: 6 | Views: 9203 | Votes: 0 | Shared: 0
Location: Pune, Maharashtra, India | Leaked: May-15-2008 in News
New Cartoon Controversy Angers Hindus
Okay, so it isn't the Hindus who are angry. Is it any surprise that Islamists have found a new reason to kill infidels? The first cartoon is a Berkeley Breathed "Opus" cartoon newspapers throughout
By: DMartyr | Comments: 23 | Views: 9676 | Votes: 2 | Shared: 0
Leaked: Aug-27-2007 in Iran, News